
- <Centre d'Information et de documentation du CRA Rhône-Alpes
- CRA
- Informations pratiques
-
Adresse
Centre d'information et de documentation
Horaires
du CRA Rhône-Alpes
Centre Hospitalier le Vinatier
bât 211
95, Bd Pinel
69678 Bron CedexLundi au Vendredi
Contact
9h00-12h00 13h30-16h00Tél: +33(0)4 37 91 54 65
Mail
Fax: +33(0)4 37 91 54 37
-
Adresse
|
[n° ou bulletin]
[n° ou bulletin]
13 - 2022 [Texte imprimé et/ou numérique] . - 2022. Langues : Anglais (eng)
|
Exemplaires
Code-barres | Cote | Support | Localisation | Section | Disponibilité |
---|---|---|---|---|---|
aucun exemplaire |
Dépouillements


Rescuing epileptic and behavioral alterations in a Dravet syndrome mouse model by inhibiting eukaryotic elongation factor 2 kinase (eEF2K) / S. BERETTA in Molecular Autism, 13 (2022)
![]()
[article]
Titre : Rescuing epileptic and behavioral alterations in a Dravet syndrome mouse model by inhibiting eukaryotic elongation factor 2 kinase (eEF2K) Type de document : Texte imprimé et/ou numérique Auteurs : S. BERETTA, Auteur ; L. GRITTI, Auteur ; L. PONZONI, Auteur ; P. SCALMANI, Auteur ; M. MANTEGAZZA, Auteur ; M. SALA, Auteur ; C. VERPELLI, Auteur ; C. SALA, Auteur Article en page(s) : 1p. Langues : Anglais (eng) Mots-clés : Eeg Inhibitory synapses Protein translation SCN1A gene Index. décimale : PER Périodiques Résumé : BACKGROUND: Dravet Syndrome is a severe childhood pharmaco-resistant epileptic disorder mainly caused by mutations in the SCN1A gene, which encodes for the ?1 subunit of the type I voltage-gated sodium channel (Na(V)1.1), that causes imbalance between excitation and inhibition in the brain. We recently found that eEF2K knock out mice displayed enhanced GABAergic transmission and tonic inhibition and were less susceptible to epileptic seizures. Thus, we investigated the effect of inhibition of eEF2K on the epileptic and behavioral phenotype of Scn1a?±?mice, a murine model of Dravet Syndrome. METHODS: To elucidate the role of eEF2K pathway in the etiopathology of Dravet syndrome we generated a new mouse model deleting the eEF2K gene in Scn1a?±?mice. By crossing Scn1a?±?mice with eEF2K-/- mice we obtained the three main genotypes needed for our studies, Scn1a+/+ eEF2K+/+ (WT mice), Scn1a?±?eEF2K+/+ mice (Scn1a?±?mice) and Scn1a?±?eEF2K-/- mice, that were fully characterized for EEG and behavioral phenotype. Furthermore, we tested the ability of a pharmacological inhibitor of eEF2K in rescuing EEG alterations of the Scn1a?±?mice. RESULTS: We showed that the activity of eEF2K/eEF2 pathway was enhanced in Scn1a?±?mice. Then, we demonstrated that both genetic deletion and pharmacological inhibition of eEF2K were sufficient to ameliorate the epileptic phenotype of Scn1a?±?mice. Interestingly we also found that motor coordination defect, memory impairments, and stereotyped behavior of the Scn1a?±?mice were reverted by eEF2K deletion. The analysis of spontaneous inhibitory postsynaptic currents (sIPSCs) suggested that the rescue of the pathological phenotype was driven by the potentiation of GABAergic synapses. LIMITATIONS: Even if we found that eEF2K deletion was able to increase inhibitory synapses function, the molecular mechanism underlining the inhibition of eEF2K/eEF2 pathway in rescuing epileptic and behavioral alterations in the Scn1a?±?needs further investigations. CONCLUSIONS: Our data indicate that pharmacological inhibition of eEF2K could represent a novel therapeutic intervention for treating epilepsy and related comorbidities in the Dravet syndrome. En ligne : http://dx.doi.org/10.1186/s13229-021-00484-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459
in Molecular Autism > 13 (2022) . - 1p.[article] Rescuing epileptic and behavioral alterations in a Dravet syndrome mouse model by inhibiting eukaryotic elongation factor 2 kinase (eEF2K) [Texte imprimé et/ou numérique] / S. BERETTA, Auteur ; L. GRITTI, Auteur ; L. PONZONI, Auteur ; P. SCALMANI, Auteur ; M. MANTEGAZZA, Auteur ; M. SALA, Auteur ; C. VERPELLI, Auteur ; C. SALA, Auteur . - 1p.
Langues : Anglais (eng)
in Molecular Autism > 13 (2022) . - 1p.
Mots-clés : Eeg Inhibitory synapses Protein translation SCN1A gene Index. décimale : PER Périodiques Résumé : BACKGROUND: Dravet Syndrome is a severe childhood pharmaco-resistant epileptic disorder mainly caused by mutations in the SCN1A gene, which encodes for the ?1 subunit of the type I voltage-gated sodium channel (Na(V)1.1), that causes imbalance between excitation and inhibition in the brain. We recently found that eEF2K knock out mice displayed enhanced GABAergic transmission and tonic inhibition and were less susceptible to epileptic seizures. Thus, we investigated the effect of inhibition of eEF2K on the epileptic and behavioral phenotype of Scn1a?±?mice, a murine model of Dravet Syndrome. METHODS: To elucidate the role of eEF2K pathway in the etiopathology of Dravet syndrome we generated a new mouse model deleting the eEF2K gene in Scn1a?±?mice. By crossing Scn1a?±?mice with eEF2K-/- mice we obtained the three main genotypes needed for our studies, Scn1a+/+ eEF2K+/+ (WT mice), Scn1a?±?eEF2K+/+ mice (Scn1a?±?mice) and Scn1a?±?eEF2K-/- mice, that were fully characterized for EEG and behavioral phenotype. Furthermore, we tested the ability of a pharmacological inhibitor of eEF2K in rescuing EEG alterations of the Scn1a?±?mice. RESULTS: We showed that the activity of eEF2K/eEF2 pathway was enhanced in Scn1a?±?mice. Then, we demonstrated that both genetic deletion and pharmacological inhibition of eEF2K were sufficient to ameliorate the epileptic phenotype of Scn1a?±?mice. Interestingly we also found that motor coordination defect, memory impairments, and stereotyped behavior of the Scn1a?±?mice were reverted by eEF2K deletion. The analysis of spontaneous inhibitory postsynaptic currents (sIPSCs) suggested that the rescue of the pathological phenotype was driven by the potentiation of GABAergic synapses. LIMITATIONS: Even if we found that eEF2K deletion was able to increase inhibitory synapses function, the molecular mechanism underlining the inhibition of eEF2K/eEF2 pathway in rescuing epileptic and behavioral alterations in the Scn1a?±?needs further investigations. CONCLUSIONS: Our data indicate that pharmacological inhibition of eEF2K could represent a novel therapeutic intervention for treating epilepsy and related comorbidities in the Dravet syndrome. En ligne : http://dx.doi.org/10.1186/s13229-021-00484-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459 Autism screening at 18 months of age: a comparison of the Q-CHAT-10 and M-CHAT screeners / R. STURNER in Molecular Autism, 13 (2022)
![]()
[article]
Titre : Autism screening at 18 months of age: a comparison of the Q-CHAT-10 and M-CHAT screeners Type de document : Texte imprimé et/ou numérique Auteurs : R. STURNER, Auteur ; B. HOWARD, Auteur ; P. BERGMANN, Auteur ; S. ATTAR, Auteur ; L. STEWART-ARTZ, Auteur ; K. BET, Auteur ; Carrie ALLISON, Auteur ; Simon BARON-COHEN, Auteur Article en page(s) : 2p. Langues : Anglais (eng) Mots-clés : Autism screening Developmental screening M-chat Q-CHAT Primary Care and its for-profit subsidiary, CHADIS, Inc. CHADIS, the web-tool used in the study was developed by Dr. Sturner and his spouse, Dr. Howard. Dr. Sturner is Director of the Center and Dr. Howard is President of CHADIS, Inc. Both are members of the Board of Directors of Center and are paid employees or consultants to both entities. The other authors have indicated they have no financial relationships relevant to this article to disclose. Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism screening is recommended at 18- and 24-month pediatric well visits. The Modified Checklist for Autism in Toddlers-Revised (M-CHAT-R) authors recommend a follow-up interview (M-CHAT-R/F) when positive. M-CHAT-R/F may be less accurate for 18-month-olds than 24-month-olds and accuracy for identification prior to two years is not known in samples that include children screening negative. Since autism symptoms may emerge gradually, ordinally scoring items based on the full range of response options, such as in the 10-item version of the Quantitative Checklist for Autism in Toddlers (Q-CHAT-10), might better capture autism signs than the dichotomous (i.e., yes/no) items in M-CHAT-R or the pass/fail scoring of Q-CHAT-10 items. The aims of this study were to determine and compare the accuracy of the M-CHAT-R/F and the Q-CHAT-10 and to describe the accuracy of the ordinally scored Q-CHAT-10 (Q-CHAT-10-O) for predicting autism in a sample of children who were screened at 18 months. METHODS: This is a community pediatrics validation study with screen positive (n?=?167) and age- and practice-matched screen negative children (n?=?241) recruited for diagnostic evaluations completed prior to 2 years old. Clinical diagnosis of autism was based on results of in-person diagnostic autism evaluations by research reliable testers blind to screening results and using the Autism Diagnostic Observation Schedule-Second Edition (ADOS-2) Toddler Module and Mullen Scales of Early Learning (MSEL) per standard guidelines. RESULTS: While the M-CHAT-R/F had higher specificity and PPV compared to M-CHAT-R, Q-CHAT-10-O showed higher sensitivity than M-CHAT-R/F and Q-CHAT-10. LIMITATIONS: Many parents declined participation and the sample is over-represented by higher educated parents. Results cannot be extended to older ages. CONCLUSIONS: Limitations of the currently recommended two-stage M-CHAT-R/F at the 18-month visit include low sensitivity with minimal balancing benefit of improved PPV from the follow-up interview. Ordinal, rather than dichotomous, scoring of autism screening items appears to be beneficial at this age. The Q-CHAT-10-O with ordinal scoring shows advantages to M-CHAT-R/F with half the number of items, no requirement for a follow-up interview, and improved sensitivity. Yet, Q-CHAT-10-O sensitivity is less than M-CHAT-R (without follow-up) and specificity is less than the two-stage procedure. Such limitations are consistent with recognition that screening needs to recur beyond this age. En ligne : http://dx.doi.org/10.1186/s13229-021-00480-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459
in Molecular Autism > 13 (2022) . - 2p.[article] Autism screening at 18 months of age: a comparison of the Q-CHAT-10 and M-CHAT screeners [Texte imprimé et/ou numérique] / R. STURNER, Auteur ; B. HOWARD, Auteur ; P. BERGMANN, Auteur ; S. ATTAR, Auteur ; L. STEWART-ARTZ, Auteur ; K. BET, Auteur ; Carrie ALLISON, Auteur ; Simon BARON-COHEN, Auteur . - 2p.
Langues : Anglais (eng)
in Molecular Autism > 13 (2022) . - 2p.
Mots-clés : Autism screening Developmental screening M-chat Q-CHAT Primary Care and its for-profit subsidiary, CHADIS, Inc. CHADIS, the web-tool used in the study was developed by Dr. Sturner and his spouse, Dr. Howard. Dr. Sturner is Director of the Center and Dr. Howard is President of CHADIS, Inc. Both are members of the Board of Directors of Center and are paid employees or consultants to both entities. The other authors have indicated they have no financial relationships relevant to this article to disclose. Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism screening is recommended at 18- and 24-month pediatric well visits. The Modified Checklist for Autism in Toddlers-Revised (M-CHAT-R) authors recommend a follow-up interview (M-CHAT-R/F) when positive. M-CHAT-R/F may be less accurate for 18-month-olds than 24-month-olds and accuracy for identification prior to two years is not known in samples that include children screening negative. Since autism symptoms may emerge gradually, ordinally scoring items based on the full range of response options, such as in the 10-item version of the Quantitative Checklist for Autism in Toddlers (Q-CHAT-10), might better capture autism signs than the dichotomous (i.e., yes/no) items in M-CHAT-R or the pass/fail scoring of Q-CHAT-10 items. The aims of this study were to determine and compare the accuracy of the M-CHAT-R/F and the Q-CHAT-10 and to describe the accuracy of the ordinally scored Q-CHAT-10 (Q-CHAT-10-O) for predicting autism in a sample of children who were screened at 18 months. METHODS: This is a community pediatrics validation study with screen positive (n?=?167) and age- and practice-matched screen negative children (n?=?241) recruited for diagnostic evaluations completed prior to 2 years old. Clinical diagnosis of autism was based on results of in-person diagnostic autism evaluations by research reliable testers blind to screening results and using the Autism Diagnostic Observation Schedule-Second Edition (ADOS-2) Toddler Module and Mullen Scales of Early Learning (MSEL) per standard guidelines. RESULTS: While the M-CHAT-R/F had higher specificity and PPV compared to M-CHAT-R, Q-CHAT-10-O showed higher sensitivity than M-CHAT-R/F and Q-CHAT-10. LIMITATIONS: Many parents declined participation and the sample is over-represented by higher educated parents. Results cannot be extended to older ages. CONCLUSIONS: Limitations of the currently recommended two-stage M-CHAT-R/F at the 18-month visit include low sensitivity with minimal balancing benefit of improved PPV from the follow-up interview. Ordinal, rather than dichotomous, scoring of autism screening items appears to be beneficial at this age. The Q-CHAT-10-O with ordinal scoring shows advantages to M-CHAT-R/F with half the number of items, no requirement for a follow-up interview, and improved sensitivity. Yet, Q-CHAT-10-O sensitivity is less than M-CHAT-R (without follow-up) and specificity is less than the two-stage procedure. Such limitations are consistent with recognition that screening needs to recur beyond this age. En ligne : http://dx.doi.org/10.1186/s13229-021-00480-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459 Delineating the autistic phenotype in children with neurofibromatosis type 1 / A. K. CHISHOLM in Molecular Autism, 13 (2022)
![]()
[article]
Titre : Delineating the autistic phenotype in children with neurofibromatosis type 1 Type de document : Texte imprimé et/ou numérique Auteurs : A. K. CHISHOLM, Auteur ; K. M. HAEBICH, Auteur ; N. A. PRIDE, Auteur ; K. S. WALSH, Auteur ; F. LAMI, Auteur ; A. URE, Auteur ; T. MALOOF, Auteur ; Amanda BRIGNELL, Auteur ; M. ROUEL, Auteur ; Y. GRANADER, Auteur ; A. MAIER, Auteur ; B. BARTON, Auteur ; H. DARKE, Auteur ; G. DABSCHECK, Auteur ; V. A. ANDERSON, Auteur ; K. WILLIAMS, Auteur ; K. N. NORTH, Auteur ; J. M. PAYNE, Auteur Article en page(s) : 3p. Langues : Anglais (eng) Mots-clés : Autism Autism Diagnostic Interview-Revised (ADI-R) Autism Diagnostic Observation Schedule-Second Edition (ADOS-2) Autistic behaviours Neurofibromatosis type 1 Index. décimale : PER Périodiques Résumé : BACKGROUND: Existing research has demonstrated elevated autistic behaviours in children with neurofibromatosis type 1 (NF1), but the autistic phenotype and its relationship to other neurodevelopmental manifestations of NF1 remains unclear. To address this gap, we performed detailed characterisation of autistic behaviours in children with NF1 and investigated their association with other common NF1 child characteristics. METHODS: Participants were drawn from a larger cross-sectional study examining autism in children with NF1. The population analysed in this study scored above threshold on the Social Responsiveness Scale-Second Edition (T-score???60; 51% larger cohort) and completed the Autism Diagnostic Interview-Revised (ADI-R) and/or the Autism Diagnostic Observation Schedule-Second Edition (ADOS-2). All participants underwent evaluation of their intellectual function, and behavioural data were collected via parent questionnaires. RESULTS: The study cohort comprised 68 children (3-15 years). Sixty-three per cent met the ADOS-2 'autism spectrum' cut-off, and 34% exceeded the more stringent threshold for 'autistic disorder' on the ADI-R. Social communication symptoms were common and wide-ranging, while restricted and repetitive behaviours (RRBs) were most commonly characterised by 'insistence on sameness' (IS) behaviours such as circumscribed interests and difficulties with minor changes. Autistic behaviours were weakly correlated with hyperactive/impulsive attention deficit hyperactivity disorder (ADHD) symptoms but not with inattentive ADHD or other behavioural characteristics. Language and verbal IQ were weakly related to social communication behaviours but not to RRBs. LIMITATIONS: Lack of genetic validation of NF1, no clinical diagnosis of autism, and a retrospective assessment of autistic behaviours in early childhood. CONCLUSIONS: Findings provide strong support for elevated autistic behaviours in children with NF1. While these behaviours were relatively independent of other NF1 comorbidities, the importance of taking broader child characteristics into consideration when interpreting data from autism-specific measures in this population is highlighted. Social communication deficits appear similar to those observed in idiopathic autism and are coupled with a unique RRB profile comprising prominent IS behaviours. This autistic phenotype and its relationship to common NF1 comorbidities such as anxiety and executive dysfunction will be important to examine in future research. Current findings have important implications for the early identification of autism in NF1 and clinical management. En ligne : http://dx.doi.org/10.1186/s13229-021-00481-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459
in Molecular Autism > 13 (2022) . - 3p.[article] Delineating the autistic phenotype in children with neurofibromatosis type 1 [Texte imprimé et/ou numérique] / A. K. CHISHOLM, Auteur ; K. M. HAEBICH, Auteur ; N. A. PRIDE, Auteur ; K. S. WALSH, Auteur ; F. LAMI, Auteur ; A. URE, Auteur ; T. MALOOF, Auteur ; Amanda BRIGNELL, Auteur ; M. ROUEL, Auteur ; Y. GRANADER, Auteur ; A. MAIER, Auteur ; B. BARTON, Auteur ; H. DARKE, Auteur ; G. DABSCHECK, Auteur ; V. A. ANDERSON, Auteur ; K. WILLIAMS, Auteur ; K. N. NORTH, Auteur ; J. M. PAYNE, Auteur . - 3p.
Langues : Anglais (eng)
in Molecular Autism > 13 (2022) . - 3p.
Mots-clés : Autism Autism Diagnostic Interview-Revised (ADI-R) Autism Diagnostic Observation Schedule-Second Edition (ADOS-2) Autistic behaviours Neurofibromatosis type 1 Index. décimale : PER Périodiques Résumé : BACKGROUND: Existing research has demonstrated elevated autistic behaviours in children with neurofibromatosis type 1 (NF1), but the autistic phenotype and its relationship to other neurodevelopmental manifestations of NF1 remains unclear. To address this gap, we performed detailed characterisation of autistic behaviours in children with NF1 and investigated their association with other common NF1 child characteristics. METHODS: Participants were drawn from a larger cross-sectional study examining autism in children with NF1. The population analysed in this study scored above threshold on the Social Responsiveness Scale-Second Edition (T-score???60; 51% larger cohort) and completed the Autism Diagnostic Interview-Revised (ADI-R) and/or the Autism Diagnostic Observation Schedule-Second Edition (ADOS-2). All participants underwent evaluation of their intellectual function, and behavioural data were collected via parent questionnaires. RESULTS: The study cohort comprised 68 children (3-15 years). Sixty-three per cent met the ADOS-2 'autism spectrum' cut-off, and 34% exceeded the more stringent threshold for 'autistic disorder' on the ADI-R. Social communication symptoms were common and wide-ranging, while restricted and repetitive behaviours (RRBs) were most commonly characterised by 'insistence on sameness' (IS) behaviours such as circumscribed interests and difficulties with minor changes. Autistic behaviours were weakly correlated with hyperactive/impulsive attention deficit hyperactivity disorder (ADHD) symptoms but not with inattentive ADHD or other behavioural characteristics. Language and verbal IQ were weakly related to social communication behaviours but not to RRBs. LIMITATIONS: Lack of genetic validation of NF1, no clinical diagnosis of autism, and a retrospective assessment of autistic behaviours in early childhood. CONCLUSIONS: Findings provide strong support for elevated autistic behaviours in children with NF1. While these behaviours were relatively independent of other NF1 comorbidities, the importance of taking broader child characteristics into consideration when interpreting data from autism-specific measures in this population is highlighted. Social communication deficits appear similar to those observed in idiopathic autism and are coupled with a unique RRB profile comprising prominent IS behaviours. This autistic phenotype and its relationship to common NF1 comorbidities such as anxiety and executive dysfunction will be important to examine in future research. Current findings have important implications for the early identification of autism in NF1 and clinical management. En ligne : http://dx.doi.org/10.1186/s13229-021-00481-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459 Correction to: Visual attention and inhibitory control in children, teenagers and adults with autism without intellectual disability: results of oculomotor tasks from a 2-year longitudinal follow-up study (InFoR) / Anouck AMESTOY in Molecular Autism, 13 (2022)
![]()
[article]
Titre : Correction to: Visual attention and inhibitory control in children, teenagers and adults with autism without intellectual disability: results of oculomotor tasks from a 2-year longitudinal follow-up study (InFoR) Type de document : Texte imprimé et/ou numérique Auteurs : Anouck AMESTOY, Auteur ; E. GUILLAUD, Auteur ; G. BUCCHIONI, Auteur ; T. ZALLA, Auteur ; D. UMBRICHT, Auteur ; Christopher H. CHATHAM, Auteur ; L. MURTAGH, Auteur ; J. HOUENOU, Auteur ; R. DELORME, Auteur ; M. L. MOAL, Auteur ; M. LEBOYER, Auteur ; Manuel P. BOUVARD, Auteur ; J. R. CAZALETS, Auteur Article en page(s) : 4p. Langues : Anglais (eng) Index. décimale : PER Périodiques En ligne : http://dx.doi.org/10.1186/s13229-021-00479-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459
in Molecular Autism > 13 (2022) . - 4p.[article] Correction to: Visual attention and inhibitory control in children, teenagers and adults with autism without intellectual disability: results of oculomotor tasks from a 2-year longitudinal follow-up study (InFoR) [Texte imprimé et/ou numérique] / Anouck AMESTOY, Auteur ; E. GUILLAUD, Auteur ; G. BUCCHIONI, Auteur ; T. ZALLA, Auteur ; D. UMBRICHT, Auteur ; Christopher H. CHATHAM, Auteur ; L. MURTAGH, Auteur ; J. HOUENOU, Auteur ; R. DELORME, Auteur ; M. L. MOAL, Auteur ; M. LEBOYER, Auteur ; Manuel P. BOUVARD, Auteur ; J. R. CAZALETS, Auteur . - 4p.
Langues : Anglais (eng)
in Molecular Autism > 13 (2022) . - 4p.
Index. décimale : PER Périodiques En ligne : http://dx.doi.org/10.1186/s13229-021-00479-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459 Friend matters: sex differences in social language during autism diagnostic interviews / M. COLA in Molecular Autism, 13 (2022)
![]()
[article]
Titre : Friend matters: sex differences in social language during autism diagnostic interviews Type de document : Texte imprimé et/ou numérique Auteurs : M. COLA, Auteur ; L. D. YANKOWITZ, Auteur ; K. TENA, Auteur ; A. RUSSELL, Auteur ; Leila BATEMAN, Auteur ; A. KNOX, Auteur ; S. PLATE, Auteur ; L. S. CUBIT, Auteur ; C. J. ZAMPELLA, Auteur ; J. PANDEY, Auteur ; Robert T. SCHULTZ, Auteur ; Julia PARISH-MORRIS, Auteur Article en page(s) : 5p. Langues : Anglais (eng) Mots-clés : Autism spectrum condition Autism spectrum disorder Language Sex differences Social phenotype Index. décimale : PER Périodiques Résumé : BACKGROUND: Autistic individuals frequently experience social communication challenges. Girls are diagnosed with autism less often than boys even when their symptoms are equally severe, which may be due to insufficient understanding of the way autism manifests in girls. Differences in the behavioral presentation of autism, including how people talk about social topics, could contribute to these persistent problems with identification. Despite a growing body of research suggesting that autistic girls and boys present distinct symptom profiles in a variety of domains, including social attention, friendships, social motivation, and language, differences in the way that autistic boys and girls communicate verbally are not yet well understood. Closely analyzing boys' and girls' socially-focused language during semi-structured clinical assessments could shed light on potential sex differences in the behavioral presentation of autistic individuals that may prove useful for identifying and effectively supporting autistic girls. Here, we compare social word use in verbally fluent autistic girls and boys during the interview sections of the ADOS-2 Module 3 and measure associations with clinical phenotype. METHODS: School-aged girls and boys with autism (N?=?101, 25 females; aged 6-15) were matched on age, IQ, and parent/clinician ratings of autism symptom severity. Our primary analysis compared the number of social words produced by autistic boys and girls (normalized to account for differences in total word production). Social words are words that make reference to other people, including friends and family. RESULTS: There was a significant main effect of sex on social word production, such that autistic girls used more social words than autistic boys. To identify the specific types of words driving this effect, additional subcategories of friend and family words were analyzed. There was a significant effect of sex on friend words, with girls using significantly more friend words than boys. However, there was no significant main effect of sex on family words, suggesting that sex differences in social word production may be driven by girls talking more about friends compared to boys, not family. To assess relationships between word use and clinical phenotype, we modeled ADOS-2 Social Affect (SA) scores as a function of social word production. In the overall sample, social word use correlated significantly with ADOS-2 SA scores, indicating that participants who used more social words were rated as less socially impaired by clinicians. However, when examined in each sex separately, this result only held for boys. LIMITATIONS: This study cannot speak to the ways in which social word use may differ for younger children, adults, or individuals who are not verbally fluent; in addition, there were more autistic boys than girls in our sample, making it difficult to detect small effects. CONCLUSIONS: Autistic girls used significantly more social words than boys during a diagnostic assessment-despite being matched on age, IQ, and both parent- and clinician-rated autism symptom severity. Sex differences in linguistic markers of social phenotype in autism are especially important in light of the late or missed diagnoses that disproportionately affect autistic girls. Specifically, heightened talk about social topics could complicate autism referral and diagnosis when non-clinician observers expect a male-typical pattern of reduced social focus, which autistic girls may not always exhibit. En ligne : http://dx.doi.org/10.1186/s13229-021-00483-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459
in Molecular Autism > 13 (2022) . - 5p.[article] Friend matters: sex differences in social language during autism diagnostic interviews [Texte imprimé et/ou numérique] / M. COLA, Auteur ; L. D. YANKOWITZ, Auteur ; K. TENA, Auteur ; A. RUSSELL, Auteur ; Leila BATEMAN, Auteur ; A. KNOX, Auteur ; S. PLATE, Auteur ; L. S. CUBIT, Auteur ; C. J. ZAMPELLA, Auteur ; J. PANDEY, Auteur ; Robert T. SCHULTZ, Auteur ; Julia PARISH-MORRIS, Auteur . - 5p.
Langues : Anglais (eng)
in Molecular Autism > 13 (2022) . - 5p.
Mots-clés : Autism spectrum condition Autism spectrum disorder Language Sex differences Social phenotype Index. décimale : PER Périodiques Résumé : BACKGROUND: Autistic individuals frequently experience social communication challenges. Girls are diagnosed with autism less often than boys even when their symptoms are equally severe, which may be due to insufficient understanding of the way autism manifests in girls. Differences in the behavioral presentation of autism, including how people talk about social topics, could contribute to these persistent problems with identification. Despite a growing body of research suggesting that autistic girls and boys present distinct symptom profiles in a variety of domains, including social attention, friendships, social motivation, and language, differences in the way that autistic boys and girls communicate verbally are not yet well understood. Closely analyzing boys' and girls' socially-focused language during semi-structured clinical assessments could shed light on potential sex differences in the behavioral presentation of autistic individuals that may prove useful for identifying and effectively supporting autistic girls. Here, we compare social word use in verbally fluent autistic girls and boys during the interview sections of the ADOS-2 Module 3 and measure associations with clinical phenotype. METHODS: School-aged girls and boys with autism (N?=?101, 25 females; aged 6-15) were matched on age, IQ, and parent/clinician ratings of autism symptom severity. Our primary analysis compared the number of social words produced by autistic boys and girls (normalized to account for differences in total word production). Social words are words that make reference to other people, including friends and family. RESULTS: There was a significant main effect of sex on social word production, such that autistic girls used more social words than autistic boys. To identify the specific types of words driving this effect, additional subcategories of friend and family words were analyzed. There was a significant effect of sex on friend words, with girls using significantly more friend words than boys. However, there was no significant main effect of sex on family words, suggesting that sex differences in social word production may be driven by girls talking more about friends compared to boys, not family. To assess relationships between word use and clinical phenotype, we modeled ADOS-2 Social Affect (SA) scores as a function of social word production. In the overall sample, social word use correlated significantly with ADOS-2 SA scores, indicating that participants who used more social words were rated as less socially impaired by clinicians. However, when examined in each sex separately, this result only held for boys. LIMITATIONS: This study cannot speak to the ways in which social word use may differ for younger children, adults, or individuals who are not verbally fluent; in addition, there were more autistic boys than girls in our sample, making it difficult to detect small effects. CONCLUSIONS: Autistic girls used significantly more social words than boys during a diagnostic assessment-despite being matched on age, IQ, and both parent- and clinician-rated autism symptom severity. Sex differences in linguistic markers of social phenotype in autism are especially important in light of the late or missed diagnoses that disproportionately affect autistic girls. Specifically, heightened talk about social topics could complicate autism referral and diagnosis when non-clinician observers expect a male-typical pattern of reduced social focus, which autistic girls may not always exhibit. En ligne : http://dx.doi.org/10.1186/s13229-021-00483-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459 A proof-of-concept study of growth hormone in children with Phelan-McDermid syndrome / S. SETHURAM in Molecular Autism, 13 (2022)
![]()
[article]
Titre : A proof-of-concept study of growth hormone in children with Phelan-McDermid syndrome Type de document : Texte imprimé et/ou numérique Auteurs : S. SETHURAM, Auteur ; T. LEVY, Auteur ; J. FOSS-FEIG, Auteur ; Danielle B. HALPERN, Auteur ; S. SANDIN, Auteur ; P. M. SIPER, Auteur ; H. WALKER, Auteur ; Joseph D. BUXBAUM, Auteur ; R. RAPAPORT, Auteur ; A. KOLEVZON, Auteur Article en page(s) : 6p. Langues : Anglais (eng) Mots-clés : Asd Autism spectrum disorder Growth hormone Igf-1 Insulin-like growth factor-1 Pms Phelan–McDermid syndrome Shank3 Jaguar, Neuren, GW Pharma, and Ovid Therapeutics. JDB has a shared patent with Mount Sinai for IGF-1 in Phelan–McDermid syndrome. No other authors have competing interests to disclose. Index. décimale : PER Périodiques Résumé : BACKGROUND: Phelan-McDermid syndrome (PMS) is caused by 22q13 deletions including SHANK3 or pathogenic sequence variants in SHANK3 and is among the more common rare genetic findings in autism spectrum disorder (ASD). SHANK3 is critical for synaptic function, and preclinical and clinical studies suggest that insulin-like growth factor-1 (IGF-1) can reverse a range of deficits in PMS. IGF-1 release is stimulated by growth hormone secretion from the anterior pituitary gland, and this study sought to assess the feasibility of increasing IGF-1 levels through recombinant human growth hormone (rhGH) treatment, in addition to establishing safety and exploring efficacy of rhGH in children with PMS. METHODS: rhGH was administered once daily for 12 weeks to six children with PMS using an open-label design. IGF-1 levels, safety, and efficacy assessments were measured every 4 weeks throughout the study. RESULTS: rhGH administration increased levels of IGF-1 by at least 2 standard deviations and was well tolerated without serious adverse events. rhGH treatment was also associated with clinical improvement in social withdrawal, hyperactivity, and sensory symptoms. LIMITATIONS: Results should be interpreted with caution given the small sample size and lack of a placebo control. CONCLUSIONS: Overall, findings are promising and indicate the need for larger studies with rhGH in PMS. Trial registration NCT04003207. Registered July 1, 2019, https://clinicaltrials.gov/ct2/show/NCT04003207 . En ligne : http://dx.doi.org/10.1186/s13229-022-00485-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459
in Molecular Autism > 13 (2022) . - 6p.[article] A proof-of-concept study of growth hormone in children with Phelan-McDermid syndrome [Texte imprimé et/ou numérique] / S. SETHURAM, Auteur ; T. LEVY, Auteur ; J. FOSS-FEIG, Auteur ; Danielle B. HALPERN, Auteur ; S. SANDIN, Auteur ; P. M. SIPER, Auteur ; H. WALKER, Auteur ; Joseph D. BUXBAUM, Auteur ; R. RAPAPORT, Auteur ; A. KOLEVZON, Auteur . - 6p.
Langues : Anglais (eng)
in Molecular Autism > 13 (2022) . - 6p.
Mots-clés : Asd Autism spectrum disorder Growth hormone Igf-1 Insulin-like growth factor-1 Pms Phelan–McDermid syndrome Shank3 Jaguar, Neuren, GW Pharma, and Ovid Therapeutics. JDB has a shared patent with Mount Sinai for IGF-1 in Phelan–McDermid syndrome. No other authors have competing interests to disclose. Index. décimale : PER Périodiques Résumé : BACKGROUND: Phelan-McDermid syndrome (PMS) is caused by 22q13 deletions including SHANK3 or pathogenic sequence variants in SHANK3 and is among the more common rare genetic findings in autism spectrum disorder (ASD). SHANK3 is critical for synaptic function, and preclinical and clinical studies suggest that insulin-like growth factor-1 (IGF-1) can reverse a range of deficits in PMS. IGF-1 release is stimulated by growth hormone secretion from the anterior pituitary gland, and this study sought to assess the feasibility of increasing IGF-1 levels through recombinant human growth hormone (rhGH) treatment, in addition to establishing safety and exploring efficacy of rhGH in children with PMS. METHODS: rhGH was administered once daily for 12 weeks to six children with PMS using an open-label design. IGF-1 levels, safety, and efficacy assessments were measured every 4 weeks throughout the study. RESULTS: rhGH administration increased levels of IGF-1 by at least 2 standard deviations and was well tolerated without serious adverse events. rhGH treatment was also associated with clinical improvement in social withdrawal, hyperactivity, and sensory symptoms. LIMITATIONS: Results should be interpreted with caution given the small sample size and lack of a placebo control. CONCLUSIONS: Overall, findings are promising and indicate the need for larger studies with rhGH in PMS. Trial registration NCT04003207. Registered July 1, 2019, https://clinicaltrials.gov/ct2/show/NCT04003207 . En ligne : http://dx.doi.org/10.1186/s13229-022-00485-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459 Autism and chronic ill health: an observational study of symptoms and diagnoses of central sensitivity syndromes in autistic adults / S. GRANT in Molecular Autism, 13 (2022)
![]()
[article]
Titre : Autism and chronic ill health: an observational study of symptoms and diagnoses of central sensitivity syndromes in autistic adults Type de document : Texte imprimé et/ou numérique Auteurs : S. GRANT, Auteur ; S. NORTON, Auteur ; R. F. WEILAND, Auteur ; Anke M. SCHEEREN, Auteur ; Sander BEGEER, Auteur ; R. A. HOEKSTRA, Auteur Article en page(s) : 7p. Langues : Anglais (eng) Mots-clés : Autism Central sensitisation Chronic pain Fatigue Fibromyalgia Sensory processing Sensory sensitivity Index. décimale : PER Périodiques Résumé : BACKGROUND: Autistic adults, particularly women, are more likely to experience chronic ill health than the general population. Central sensitivity syndromes (CSS) are a group of related conditions that are thought to include an underlying sensitisation of the central nervous system; heightened sensory sensitivity is a common feature. Anecdotal evidence suggests autistic adults may be more prone to developing a CSS. This study aimed to investigate the occurrence of CSS diagnoses and symptoms in autistic adults, and to explore whether CSS symptoms were related to autistic traits, mental health, sensory sensitivity, or gender. METHODS: The full sample of participants included 973 autistic adults (410 men, 563 women, mean age?=?44.6) registered at the Netherlands Autism Register, who completed questionnaires assessing autistic traits, sensory sensitivity, CSS, physical and mental health symptoms. The reliability and validity of the Central Sensitization Inventory (CSI) in an autistic sample was established using exploratory and confirmatory factor analyses. Chi(2) analyses, independent t-tests, hierarchical regression and path analysis were used to analyse relationships between CSS symptoms, autistic traits, measures of mental health and wellbeing, sensory sensitivity, age and gender. RESULTS: 21% of participants reported one or more CSS diagnosis, and 60% scored at or above the clinical cut-off for a CSS. Autistic women were more likely to report a CSS diagnosis and experienced more CSS symptoms than men. Sensory sensitivity, anxiety, age and gender were significant predictors of CSS symptoms, with sensory sensitivity and anxiety fully mediating the relationship between autistic traits and CSS symptoms. LIMITATIONS: Although this study included a large sample of autistic adults, we did not have a control group or a CSS only group. We also could not include a non-binary group due to lack of statistical power. CONCLUSIONS: CSS diagnoses and symptoms appear to be very common in the autistic population. Increased awareness of an association between autism and central sensitisation should inform clinicians and guide diagnostic practice, particularly for women where CSS are common and autism under recognised. En ligne : http://dx.doi.org/10.1186/s13229-022-00486-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459
in Molecular Autism > 13 (2022) . - 7p.[article] Autism and chronic ill health: an observational study of symptoms and diagnoses of central sensitivity syndromes in autistic adults [Texte imprimé et/ou numérique] / S. GRANT, Auteur ; S. NORTON, Auteur ; R. F. WEILAND, Auteur ; Anke M. SCHEEREN, Auteur ; Sander BEGEER, Auteur ; R. A. HOEKSTRA, Auteur . - 7p.
Langues : Anglais (eng)
in Molecular Autism > 13 (2022) . - 7p.
Mots-clés : Autism Central sensitisation Chronic pain Fatigue Fibromyalgia Sensory processing Sensory sensitivity Index. décimale : PER Périodiques Résumé : BACKGROUND: Autistic adults, particularly women, are more likely to experience chronic ill health than the general population. Central sensitivity syndromes (CSS) are a group of related conditions that are thought to include an underlying sensitisation of the central nervous system; heightened sensory sensitivity is a common feature. Anecdotal evidence suggests autistic adults may be more prone to developing a CSS. This study aimed to investigate the occurrence of CSS diagnoses and symptoms in autistic adults, and to explore whether CSS symptoms were related to autistic traits, mental health, sensory sensitivity, or gender. METHODS: The full sample of participants included 973 autistic adults (410 men, 563 women, mean age?=?44.6) registered at the Netherlands Autism Register, who completed questionnaires assessing autistic traits, sensory sensitivity, CSS, physical and mental health symptoms. The reliability and validity of the Central Sensitization Inventory (CSI) in an autistic sample was established using exploratory and confirmatory factor analyses. Chi(2) analyses, independent t-tests, hierarchical regression and path analysis were used to analyse relationships between CSS symptoms, autistic traits, measures of mental health and wellbeing, sensory sensitivity, age and gender. RESULTS: 21% of participants reported one or more CSS diagnosis, and 60% scored at or above the clinical cut-off for a CSS. Autistic women were more likely to report a CSS diagnosis and experienced more CSS symptoms than men. Sensory sensitivity, anxiety, age and gender were significant predictors of CSS symptoms, with sensory sensitivity and anxiety fully mediating the relationship between autistic traits and CSS symptoms. LIMITATIONS: Although this study included a large sample of autistic adults, we did not have a control group or a CSS only group. We also could not include a non-binary group due to lack of statistical power. CONCLUSIONS: CSS diagnoses and symptoms appear to be very common in the autistic population. Increased awareness of an association between autism and central sensitisation should inform clinicians and guide diagnostic practice, particularly for women where CSS are common and autism under recognised. En ligne : http://dx.doi.org/10.1186/s13229-022-00486-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459 Nonshared environmental factors in the aetiology of autism and other neurodevelopmental conditions: a monozygotic co-twin control study / J. ISAKSSON in Molecular Autism, 13 (2022)
![]()
[article]
Titre : Nonshared environmental factors in the aetiology of autism and other neurodevelopmental conditions: a monozygotic co-twin control study Type de document : Texte imprimé et/ou numérique Auteurs : J. ISAKSSON, Auteur ; V. RUCHKIN, Auteur ; N. AHO, Auteur ; K. LUNDIN REMNÉLIUS, Auteur ; P. B. MARSCHIK, Auteur ; Sven BÖLTE, Auteur Article en page(s) : 8p. Langues : Anglais (eng) Mots-clés : Adhd Autism Early adversities Iq Non-shared environment Risk factors Twins Index. décimale : PER Périodiques Résumé : BACKGROUND: A significant proportion of variation in likelihood of neurodevelopmental conditions (NDCs) has been attributed to nonshared environmental (NSE) factors, although it remains unclear which NSE factors pose specific risks for certain NDCs. METHODS: A monozygotic co-twin design was applied in a sample of 224 twins (mean age?=?17.70 years, SD?=?6.28) controlling for confounders such as genes and shared environment. Generalized estimating equation models were fitted, using perinatal and postnatal indications of NSEs as exposure, operationalized both as separate risk factors and as cumulative risk loads. Categorical and dimensional operationalizations of autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), intellectual disability and other NDCs were used as outcomes. RESULTS: Birth weight discordance was associated with dimensional autism and ADHD for the smaller twin, and medication during infancy was associated with dimensional autism. Among postnatal factors scarlet fever during early childhood was associated with lower IQ. Especially autism was associated with a greater cumulative perinatal or postnatal risk load. LIMITATIONS: When exploring the associations between each condition and specific NSEs the risk of being statistically underpowered increases. Hence, we limit the reported findings on specific indicators of NSEs to trait levels and present descriptive data for categorical NDCs. CONCLUSIONS: The findings support previous research by indicating an association between exposure to perinatal and postnatal risks and subsequent NDCs within twin pairs and suggest that autism may be especially linked to accumulative early environmental risks. The findings are potentially important for developmental outcomes prognoses and may inform targeted prevention and early interventions. En ligne : http://dx.doi.org/10.1186/s13229-022-00487-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459
in Molecular Autism > 13 (2022) . - 8p.[article] Nonshared environmental factors in the aetiology of autism and other neurodevelopmental conditions: a monozygotic co-twin control study [Texte imprimé et/ou numérique] / J. ISAKSSON, Auteur ; V. RUCHKIN, Auteur ; N. AHO, Auteur ; K. LUNDIN REMNÉLIUS, Auteur ; P. B. MARSCHIK, Auteur ; Sven BÖLTE, Auteur . - 8p.
Langues : Anglais (eng)
in Molecular Autism > 13 (2022) . - 8p.
Mots-clés : Adhd Autism Early adversities Iq Non-shared environment Risk factors Twins Index. décimale : PER Périodiques Résumé : BACKGROUND: A significant proportion of variation in likelihood of neurodevelopmental conditions (NDCs) has been attributed to nonshared environmental (NSE) factors, although it remains unclear which NSE factors pose specific risks for certain NDCs. METHODS: A monozygotic co-twin design was applied in a sample of 224 twins (mean age?=?17.70 years, SD?=?6.28) controlling for confounders such as genes and shared environment. Generalized estimating equation models were fitted, using perinatal and postnatal indications of NSEs as exposure, operationalized both as separate risk factors and as cumulative risk loads. Categorical and dimensional operationalizations of autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), intellectual disability and other NDCs were used as outcomes. RESULTS: Birth weight discordance was associated with dimensional autism and ADHD for the smaller twin, and medication during infancy was associated with dimensional autism. Among postnatal factors scarlet fever during early childhood was associated with lower IQ. Especially autism was associated with a greater cumulative perinatal or postnatal risk load. LIMITATIONS: When exploring the associations between each condition and specific NSEs the risk of being statistically underpowered increases. Hence, we limit the reported findings on specific indicators of NSEs to trait levels and present descriptive data for categorical NDCs. CONCLUSIONS: The findings support previous research by indicating an association between exposure to perinatal and postnatal risks and subsequent NDCs within twin pairs and suggest that autism may be especially linked to accumulative early environmental risks. The findings are potentially important for developmental outcomes prognoses and may inform targeted prevention and early interventions. En ligne : http://dx.doi.org/10.1186/s13229-022-00487-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459 Two neuroanatomical subtypes of males with autism spectrum disorder revealed using semi-supervised machine learning / Guanlu LIU in Molecular Autism, 13 (2022)
![]()
[article]
Titre : Two neuroanatomical subtypes of males with autism spectrum disorder revealed using semi-supervised machine learning Type de document : Texte imprimé et/ou numérique Auteurs : Guanlu LIU, Auteur ; Liting SHI, Auteur ; Jianfeng QIU, Auteur ; Weizhao LU, Auteur Article en page(s) : 9 p. Langues : Anglais (eng) Mots-clés : Autism Spectrum Disorder/diagnostic imaging Female Humans Magnetic Resonance Imaging/methods Male Neuroimaging Reproducibility of Results Supervised Machine Learning Autism Magnetic resonance imaging Neurosubtyping Semi-supervised machine learning Index. décimale : PER Périodiques Résumé : BACKGROUND: Clinical and etiological varieties remain major obstacles to decompose heterogeneity in autism spectrum disorders (ASD). Recently, neuroimaging raised new hope to identify neurosubtypes of ASD for further understanding the biological mechanisms behind the disorder. METHODS: In this study, brain structural MRI data and clinical measures of 221 male subjects with ASD and 257 healthy controls were selected from 7 independent sites from the Autism Brain Image Data Exchange database (ABIDE). Heterogeneity through discriminative analysis (HYDRA), a recently-proposed semi-supervised clustering method was utilized to divide individuals with ASD into several neurosubtypes by regional volumetric measures of gray matter, white matter, and cerebrospinal fluid. Voxel-wise volume, clinical measures, dynamic resting-state functional magnetic resonance imaging (R-fMRI) measures among different neurosubtypes of ASD were explored. In addition, support vector machine (SVM) model was applied to test whether the neurosubtyping of ASD could improve diagnostic accuracy of ASD. RESULTS: Two neurosubtypes of ASD with different voxel-wise volumetric patterns were revealed. The full-scale intelligence quotient (IQ), verbal IQ, Autism Diagnostic Observation Schedule (ADOS) total scores and ADOS severity scores were significantly different between the two neurosubtypes, the total intracranial volume was correlated with performance IQ in Subtype 1 and was correlated with ADOS communication score and ADOS social score in Subtype 2. Compared with Subtype 2, Subtype 1 showed lower dynamic R-fMRI measures, lower dynamic functional architecture stability, higher mean and lower standard deviation (SD) of concordance among dynamic R-fMRI measures in cerebellum. In addition, classification accuracies between ASD neurosubtypes and healthy controls were significantly improved compared with classification accuracy between entire ASD group and healthy controls. LIMITATIONS: The present study excluded female subjects and left-handed subjects, which limited the ability to investigate the associations between these factors and the heterogeneity of ASD. CONCLUSIONS: The two distinct neuroanatomical subtypes of ASD validated by other data modalities not only adds reliability of the result, but also bridges from brain phenomenology to clinical behavior. The current neurosubtypes of ASD could facilitate understanding the neuropathology of this disorder and could be potentially used to improve clinical decision-making process and optimize treatment. En ligne : http://dx.doi.org/10.1186/s13229-022-00489-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=477
in Molecular Autism > 13 (2022) . - 9 p.[article] Two neuroanatomical subtypes of males with autism spectrum disorder revealed using semi-supervised machine learning [Texte imprimé et/ou numérique] / Guanlu LIU, Auteur ; Liting SHI, Auteur ; Jianfeng QIU, Auteur ; Weizhao LU, Auteur . - 9 p.
Langues : Anglais (eng)
in Molecular Autism > 13 (2022) . - 9 p.
Mots-clés : Autism Spectrum Disorder/diagnostic imaging Female Humans Magnetic Resonance Imaging/methods Male Neuroimaging Reproducibility of Results Supervised Machine Learning Autism Magnetic resonance imaging Neurosubtyping Semi-supervised machine learning Index. décimale : PER Périodiques Résumé : BACKGROUND: Clinical and etiological varieties remain major obstacles to decompose heterogeneity in autism spectrum disorders (ASD). Recently, neuroimaging raised new hope to identify neurosubtypes of ASD for further understanding the biological mechanisms behind the disorder. METHODS: In this study, brain structural MRI data and clinical measures of 221 male subjects with ASD and 257 healthy controls were selected from 7 independent sites from the Autism Brain Image Data Exchange database (ABIDE). Heterogeneity through discriminative analysis (HYDRA), a recently-proposed semi-supervised clustering method was utilized to divide individuals with ASD into several neurosubtypes by regional volumetric measures of gray matter, white matter, and cerebrospinal fluid. Voxel-wise volume, clinical measures, dynamic resting-state functional magnetic resonance imaging (R-fMRI) measures among different neurosubtypes of ASD were explored. In addition, support vector machine (SVM) model was applied to test whether the neurosubtyping of ASD could improve diagnostic accuracy of ASD. RESULTS: Two neurosubtypes of ASD with different voxel-wise volumetric patterns were revealed. The full-scale intelligence quotient (IQ), verbal IQ, Autism Diagnostic Observation Schedule (ADOS) total scores and ADOS severity scores were significantly different between the two neurosubtypes, the total intracranial volume was correlated with performance IQ in Subtype 1 and was correlated with ADOS communication score and ADOS social score in Subtype 2. Compared with Subtype 2, Subtype 1 showed lower dynamic R-fMRI measures, lower dynamic functional architecture stability, higher mean and lower standard deviation (SD) of concordance among dynamic R-fMRI measures in cerebellum. In addition, classification accuracies between ASD neurosubtypes and healthy controls were significantly improved compared with classification accuracy between entire ASD group and healthy controls. LIMITATIONS: The present study excluded female subjects and left-handed subjects, which limited the ability to investigate the associations between these factors and the heterogeneity of ASD. CONCLUSIONS: The two distinct neuroanatomical subtypes of ASD validated by other data modalities not only adds reliability of the result, but also bridges from brain phenomenology to clinical behavior. The current neurosubtypes of ASD could facilitate understanding the neuropathology of this disorder and could be potentially used to improve clinical decision-making process and optimize treatment. En ligne : http://dx.doi.org/10.1186/s13229-022-00489-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=477 Pharmacological and dietary-supplement treatments for autism spectrum disorder: a systematic review and network meta-analysis / Spyridon SIAFIS in Molecular Autism, 13 (2022)
![]()
[article]
Titre : Pharmacological and dietary-supplement treatments for autism spectrum disorder: a systematic review and network meta-analysis Type de document : Texte imprimé et/ou numérique Auteurs : Spyridon SIAFIS, Auteur ; O?ulcan ÇIRAY, Auteur ; Hui WU, Auteur ; Johannes SCHNEIDER-THOMA, Auteur ; Irene BIGHELLI, Auteur ; Marc KRAUSE, Auteur ; Alessandro RODOLICO, Auteur ; Anna CERASO, Auteur ; Giacomo DESTE, Auteur ; Maximilian HUHN, Auteur ; David FRAGUAS, Auteur ; Antonia SAN JOSE CACERES, Auteur ; Dimitris MAVRIDIS, Auteur ; Tony CHARMAN, Auteur ; Declan G. MURPHY, Auteur ; Mara PARELLADA, Auteur ; Celso ARANGO, Auteur ; Stefan LEUCHT, Auteur Article en page(s) : 10 p. Langues : Anglais (eng) Mots-clés : Adolescent Adult Attention Deficit Disorder with Hyperactivity Autism Spectrum Disorder/drug therapy Child Humans Network Meta-Analysis Oxytocin/therapeutic use Risperidone/therapeutic use Adhd Anxiety Autism Caregiver stress Irritability Meta-analysis Response Restricted and repetitive behaviors Social communication Treatment Index. décimale : PER Périodiques Résumé : BACKGROUND: There is still no approved medication for the core symptoms of autism spectrum disorder (ASD). This network meta-analysis investigated pharmacological and dietary-supplement treatments for ASD. METHODS: We searched for randomized-controlled-trials (RCTs) with a minimum duration of seven days in ClinicalTrials.gov, EMBASE, MEDLINE, PsycINFO, WHO-ICTRP (from inception up to July 8, 2018), CENTRAL and PubMed (up to November 3, 2021). The co-primary outcomes were core symptoms (social-communication difficulties-SCD, repetitive behaviors-RB, overall core symptoms-OCS) measured by validated scales and standardized-mean-differences (SMDs). Associated symptoms, e.g., irritability/aggression and attention-deficit/hyperactivity disorder (ADHD) symptoms, dropouts and important side-effects, were investigated as secondary outcomes. Studies in children/adolescents and adults were analyzed separately in random-effects pairwise and network meta-analyses. RESULTS: We analyzed data for 41 drugs and 17 dietary-supplements, from 125 RCTs (n=7450 participants) in children/adolescents and 18 RCTs (n=1104) in adults. The following medications could improve at least one core symptom domain in comparison with placebo: aripiprazole (k=6 studies in analysis, SCD: SMD=0.27 95% CI [0.09, 0.44], RB: 0.48 [0.26, 0.70]), atomoxetine (k=3, RB:0.49 [0.18, 0.80]), bumetanide (k=4, RB: 0.35 [0.09, 0.62], OCS: 0.61 [0.31, 0.91]), and risperidone (k=4, SCM: 0.31 [0.06, 0.55], RB: 0.60 [0.29, 0.90]; k=3, OCS: 1.18 [0.75, 1.61]) in children/adolescents; fluoxetine (k=1, RB: 1.20 [0.45, 1.96]), fluvoxamine (k=1, RB: 1.04 [0.27, 1.81]), oxytocin (k=6, RB:0.41 [0.16, 0.66]) and risperidone (k=1, RB: 0.97 [0.21,1.74]) in adults. There were some indications of improvement by carnosine, haloperidol, folinic acid, guanfacine, omega-3-fatty-acids, probiotics, sulforaphane, tideglusib and valproate, yet imprecise and not robust. Confidence in these estimates was very low or low, except moderate for oxytocin. Medications differed substantially in improving associated symptoms, and in their side-effect profiles. LIMITATIONS: Most of the studies were inadequately powered (sample sizes of 20-80 participants), with short duration (8-13 weeks), and about a third focused on associated symptoms. Networks were mainly star-shaped, and there were indications of reporting bias. There was no optimal rating scale measuring change in core symptoms. CONCLUSIONS: Some medications could improve core symptoms, although this could be likely secondary to the improvement of associated symptoms. Evidence on their efficacy and safety is preliminary; therefore, routine prescription of medications for the core symptoms cannot be recommended. Trial registration PROSPERO-ID CRD42019125317. En ligne : http://dx.doi.org/10.1186/s13229-022-00488-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=477
in Molecular Autism > 13 (2022) . - 10 p.[article] Pharmacological and dietary-supplement treatments for autism spectrum disorder: a systematic review and network meta-analysis [Texte imprimé et/ou numérique] / Spyridon SIAFIS, Auteur ; O?ulcan ÇIRAY, Auteur ; Hui WU, Auteur ; Johannes SCHNEIDER-THOMA, Auteur ; Irene BIGHELLI, Auteur ; Marc KRAUSE, Auteur ; Alessandro RODOLICO, Auteur ; Anna CERASO, Auteur ; Giacomo DESTE, Auteur ; Maximilian HUHN, Auteur ; David FRAGUAS, Auteur ; Antonia SAN JOSE CACERES, Auteur ; Dimitris MAVRIDIS, Auteur ; Tony CHARMAN, Auteur ; Declan G. MURPHY, Auteur ; Mara PARELLADA, Auteur ; Celso ARANGO, Auteur ; Stefan LEUCHT, Auteur . - 10 p.
Langues : Anglais (eng)
in Molecular Autism > 13 (2022) . - 10 p.
Mots-clés : Adolescent Adult Attention Deficit Disorder with Hyperactivity Autism Spectrum Disorder/drug therapy Child Humans Network Meta-Analysis Oxytocin/therapeutic use Risperidone/therapeutic use Adhd Anxiety Autism Caregiver stress Irritability Meta-analysis Response Restricted and repetitive behaviors Social communication Treatment Index. décimale : PER Périodiques Résumé : BACKGROUND: There is still no approved medication for the core symptoms of autism spectrum disorder (ASD). This network meta-analysis investigated pharmacological and dietary-supplement treatments for ASD. METHODS: We searched for randomized-controlled-trials (RCTs) with a minimum duration of seven days in ClinicalTrials.gov, EMBASE, MEDLINE, PsycINFO, WHO-ICTRP (from inception up to July 8, 2018), CENTRAL and PubMed (up to November 3, 2021). The co-primary outcomes were core symptoms (social-communication difficulties-SCD, repetitive behaviors-RB, overall core symptoms-OCS) measured by validated scales and standardized-mean-differences (SMDs). Associated symptoms, e.g., irritability/aggression and attention-deficit/hyperactivity disorder (ADHD) symptoms, dropouts and important side-effects, were investigated as secondary outcomes. Studies in children/adolescents and adults were analyzed separately in random-effects pairwise and network meta-analyses. RESULTS: We analyzed data for 41 drugs and 17 dietary-supplements, from 125 RCTs (n=7450 participants) in children/adolescents and 18 RCTs (n=1104) in adults. The following medications could improve at least one core symptom domain in comparison with placebo: aripiprazole (k=6 studies in analysis, SCD: SMD=0.27 95% CI [0.09, 0.44], RB: 0.48 [0.26, 0.70]), atomoxetine (k=3, RB:0.49 [0.18, 0.80]), bumetanide (k=4, RB: 0.35 [0.09, 0.62], OCS: 0.61 [0.31, 0.91]), and risperidone (k=4, SCM: 0.31 [0.06, 0.55], RB: 0.60 [0.29, 0.90]; k=3, OCS: 1.18 [0.75, 1.61]) in children/adolescents; fluoxetine (k=1, RB: 1.20 [0.45, 1.96]), fluvoxamine (k=1, RB: 1.04 [0.27, 1.81]), oxytocin (k=6, RB:0.41 [0.16, 0.66]) and risperidone (k=1, RB: 0.97 [0.21,1.74]) in adults. There were some indications of improvement by carnosine, haloperidol, folinic acid, guanfacine, omega-3-fatty-acids, probiotics, sulforaphane, tideglusib and valproate, yet imprecise and not robust. Confidence in these estimates was very low or low, except moderate for oxytocin. Medications differed substantially in improving associated symptoms, and in their side-effect profiles. LIMITATIONS: Most of the studies were inadequately powered (sample sizes of 20-80 participants), with short duration (8-13 weeks), and about a third focused on associated symptoms. Networks were mainly star-shaped, and there were indications of reporting bias. There was no optimal rating scale measuring change in core symptoms. CONCLUSIONS: Some medications could improve core symptoms, although this could be likely secondary to the improvement of associated symptoms. Evidence on their efficacy and safety is preliminary; therefore, routine prescription of medications for the core symptoms cannot be recommended. Trial registration PROSPERO-ID CRD42019125317. En ligne : http://dx.doi.org/10.1186/s13229-022-00488-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=477 Phenotypic differences between female and male individuals with suspicion of autism spectrum disorder / Sanna STROTH in Molecular Autism, 13 (2022)
![]()
[article]
Titre : Phenotypic differences between female and male individuals with suspicion of autism spectrum disorder Type de document : Texte imprimé et/ou numérique Auteurs : Sanna STROTH, Auteur ; Johannes TAUSCHER, Auteur ; Nicole WOLFF, Auteur ; Charlotte KÜPPER, Auteur ; Luise POUSTKA, Auteur ; Stefan ROEPKE, Auteur ; Veit ROESSNER, Auteur ; Dominik HEIDER, Auteur ; Inge KAMP-BECKER, Auteur Article en page(s) : 11 p. Langues : Anglais (eng) Mots-clés : Affect Autism Spectrum Disorder/diagnosis Autistic Disorder Female Humans Intellectual Disability/diagnosis Male Adi-r Ados Asd Diagnostics Female autism Phenotype Sex Index. décimale : PER Périodiques Résumé : BACKGROUND: Although autism spectrum disorder (ASD) is a common developmental disorder, our knowledge about a behavioral and neurobiological female phenotype is still scarce. As the conceptualization and understanding of ASD are mainly based on the investigation of male individuals, females with ASD may not be adequately identified by routine clinical diagnostics. The present machine learning approach aimed to identify diagnostic information from the Autism Diagnostic Observation Schedule (ADOS) that discriminates best between ASD and non-ASD in females and males. METHODS: Random forests (RF) were used to discover patterns of symptoms in diagnostic data from the ADOS (modules 3 and 4) in 1057 participants with ASD (18.1% female) and 1230 participants with non-ASD (17.9% % female). Predictive performances of reduced feature models were explored and compared between females and males without intellectual disabilities. RESULTS: Reduced feature models relied on considerably fewer features from the ADOS in females compared to males, while still yielding similar classification performance (e.g., sensitivity, specificity). LIMITATIONS: As in previous studies, the current sample of females with ASD is smaller than the male sample and thus, females may still be underrepresented, limiting the statistical power to detect small to moderate effects. CONCLUSION: Our results do not suggest the need for new or altered diagnostic algorithms for females with ASD. Although we identified some phenotypic differences between females and males, the existing diagnostic tools seem to sufficiently capture the core autistic features in both groups. En ligne : http://dx.doi.org/10.1186/s13229-022-00491-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=477
in Molecular Autism > 13 (2022) . - 11 p.[article] Phenotypic differences between female and male individuals with suspicion of autism spectrum disorder [Texte imprimé et/ou numérique] / Sanna STROTH, Auteur ; Johannes TAUSCHER, Auteur ; Nicole WOLFF, Auteur ; Charlotte KÜPPER, Auteur ; Luise POUSTKA, Auteur ; Stefan ROEPKE, Auteur ; Veit ROESSNER, Auteur ; Dominik HEIDER, Auteur ; Inge KAMP-BECKER, Auteur . - 11 p.
Langues : Anglais (eng)
in Molecular Autism > 13 (2022) . - 11 p.
Mots-clés : Affect Autism Spectrum Disorder/diagnosis Autistic Disorder Female Humans Intellectual Disability/diagnosis Male Adi-r Ados Asd Diagnostics Female autism Phenotype Sex Index. décimale : PER Périodiques Résumé : BACKGROUND: Although autism spectrum disorder (ASD) is a common developmental disorder, our knowledge about a behavioral and neurobiological female phenotype is still scarce. As the conceptualization and understanding of ASD are mainly based on the investigation of male individuals, females with ASD may not be adequately identified by routine clinical diagnostics. The present machine learning approach aimed to identify diagnostic information from the Autism Diagnostic Observation Schedule (ADOS) that discriminates best between ASD and non-ASD in females and males. METHODS: Random forests (RF) were used to discover patterns of symptoms in diagnostic data from the ADOS (modules 3 and 4) in 1057 participants with ASD (18.1% female) and 1230 participants with non-ASD (17.9% % female). Predictive performances of reduced feature models were explored and compared between females and males without intellectual disabilities. RESULTS: Reduced feature models relied on considerably fewer features from the ADOS in females compared to males, while still yielding similar classification performance (e.g., sensitivity, specificity). LIMITATIONS: As in previous studies, the current sample of females with ASD is smaller than the male sample and thus, females may still be underrepresented, limiting the statistical power to detect small to moderate effects. CONCLUSION: Our results do not suggest the need for new or altered diagnostic algorithms for females with ASD. Although we identified some phenotypic differences between females and males, the existing diagnostic tools seem to sufficiently capture the core autistic features in both groups. En ligne : http://dx.doi.org/10.1186/s13229-022-00491-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=477 Deep phenotyping reveals movement phenotypes in mouse neurodevelopmental models / Ugne KLIBAITE in Molecular Autism, 13 (2022)
![]()
[article]
Titre : Deep phenotyping reveals movement phenotypes in mouse neurodevelopmental models Type de document : Texte imprimé et/ou numérique Auteurs : Ugne KLIBAITE, Auteur ; Mikhail KISLIN, Auteur ; Jessica L. VERPEUT, Auteur ; Silke BERGELER, Auteur ; Xiaoting SUN, Auteur ; Joshua W. SHAEVITZ, Auteur ; Samuel S.-H. WANG, Auteur Article en page(s) : 12 p. Langues : Anglais (eng) Mots-clés : Animals Autism Spectrum Disorder/genetics Disease Models, Animal Female Male Membrane Proteins/genetics Mice Mice, Inbred C57BL Mice, Knockout Nerve Tissue Proteins/genetics Phenotype Tuberous Sclerosis Complex 1 Protein/genetics Autism Behavior Cerebellum Clustering Mouse Pose estimation Index. décimale : PER Périodiques Résumé : BACKGROUND: Repetitive action, resistance to environmental change and fine motor disruptions are hallmarks of autism spectrum disorder (ASD) and other neurodevelopmental disorders, and vary considerably from individual to individual. In animal models, conventional behavioral phenotyping captures such fine-scale variations incompletely. Here we observed male and female C57BL/6J mice to methodically catalog adaptive movement over multiple days and examined two rodent models of developmental disorders against this dynamic baseline. We then investigated the behavioral consequences of a cerebellum-specific deletion in Tsc1 protein and a whole-brain knockout in Cntnap2 protein in mice. Both of these mutations are found in clinical conditions and have been associated with ASD. METHODS: We used advances in computer vision and deep learning, namely a generalized form of high-dimensional statistical analysis, to develop a framework for characterizing mouse movement on multiple timescales using a single popular behavioral assay, the open-field test. The pipeline takes virtual markers from pose estimation to find behavior clusters and generate wavelet signatures of behavior classes. We measured spatial and temporal habituation to a new environment across minutes and days, different types of self-grooming, locomotion and gait. RESULTS: Both Cntnap2 knockouts and L7-Tsc1 mutants showed forelimb lag during gait. L7-Tsc1 mutants and Cntnap2 knockouts showed complex defects in multi-day adaptation, lacking the tendency of wild-type mice to spend progressively more time in corners of the arena. In L7-Tsc1 mutant mice, failure to adapt took the form of maintained ambling, turning and locomotion, and an overall decrease in grooming. However, adaptation in these traits was similar between wild-type mice and Cntnap2 knockouts. L7-Tsc1 mutant and Cntnap2 knockout mouse models showed different patterns of behavioral state occupancy. LIMITATIONS: Genetic risk factors for autism are numerous, and we tested only two. Our pipeline was only done under conditions of free behavior. Testing under task or social conditions would reveal more information about behavioral dynamics and variability. CONCLUSIONS: Our automated pipeline for deep phenotyping successfully captures model-specific deviations in adaptation and movement as well as differences in the detailed structure of behavioral dynamics. The reported deficits indicate that deep phenotyping constitutes a robust set of ASD symptoms that may be considered for implementation in clinical settings as quantitative diagnosis criteria. En ligne : http://dx.doi.org/10.1186/s13229-022-00492-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=477
in Molecular Autism > 13 (2022) . - 12 p.[article] Deep phenotyping reveals movement phenotypes in mouse neurodevelopmental models [Texte imprimé et/ou numérique] / Ugne KLIBAITE, Auteur ; Mikhail KISLIN, Auteur ; Jessica L. VERPEUT, Auteur ; Silke BERGELER, Auteur ; Xiaoting SUN, Auteur ; Joshua W. SHAEVITZ, Auteur ; Samuel S.-H. WANG, Auteur . - 12 p.
Langues : Anglais (eng)
in Molecular Autism > 13 (2022) . - 12 p.
Mots-clés : Animals Autism Spectrum Disorder/genetics Disease Models, Animal Female Male Membrane Proteins/genetics Mice Mice, Inbred C57BL Mice, Knockout Nerve Tissue Proteins/genetics Phenotype Tuberous Sclerosis Complex 1 Protein/genetics Autism Behavior Cerebellum Clustering Mouse Pose estimation Index. décimale : PER Périodiques Résumé : BACKGROUND: Repetitive action, resistance to environmental change and fine motor disruptions are hallmarks of autism spectrum disorder (ASD) and other neurodevelopmental disorders, and vary considerably from individual to individual. In animal models, conventional behavioral phenotyping captures such fine-scale variations incompletely. Here we observed male and female C57BL/6J mice to methodically catalog adaptive movement over multiple days and examined two rodent models of developmental disorders against this dynamic baseline. We then investigated the behavioral consequences of a cerebellum-specific deletion in Tsc1 protein and a whole-brain knockout in Cntnap2 protein in mice. Both of these mutations are found in clinical conditions and have been associated with ASD. METHODS: We used advances in computer vision and deep learning, namely a generalized form of high-dimensional statistical analysis, to develop a framework for characterizing mouse movement on multiple timescales using a single popular behavioral assay, the open-field test. The pipeline takes virtual markers from pose estimation to find behavior clusters and generate wavelet signatures of behavior classes. We measured spatial and temporal habituation to a new environment across minutes and days, different types of self-grooming, locomotion and gait. RESULTS: Both Cntnap2 knockouts and L7-Tsc1 mutants showed forelimb lag during gait. L7-Tsc1 mutants and Cntnap2 knockouts showed complex defects in multi-day adaptation, lacking the tendency of wild-type mice to spend progressively more time in corners of the arena. In L7-Tsc1 mutant mice, failure to adapt took the form of maintained ambling, turning and locomotion, and an overall decrease in grooming. However, adaptation in these traits was similar between wild-type mice and Cntnap2 knockouts. L7-Tsc1 mutant and Cntnap2 knockout mouse models showed different patterns of behavioral state occupancy. LIMITATIONS: Genetic risk factors for autism are numerous, and we tested only two. Our pipeline was only done under conditions of free behavior. Testing under task or social conditions would reveal more information about behavioral dynamics and variability. CONCLUSIONS: Our automated pipeline for deep phenotyping successfully captures model-specific deviations in adaptation and movement as well as differences in the detailed structure of behavioral dynamics. The reported deficits indicate that deep phenotyping constitutes a robust set of ASD symptoms that may be considered for implementation in clinical settings as quantitative diagnosis criteria. En ligne : http://dx.doi.org/10.1186/s13229-022-00492-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=477 Dietary zinc supplementation rescues fear-based learning and synaptic function in the Tbr1(+/-) mouse model of autism spectrum disorders / Kevin LEE in Molecular Autism, 13 (2022)
![]()
[article]
Titre : Dietary zinc supplementation rescues fear-based learning and synaptic function in the Tbr1(+/-) mouse model of autism spectrum disorders Type de document : Texte imprimé et/ou numérique Auteurs : Kevin LEE, Auteur ; Yewon JUNG, Auteur ; Yukti VYAS, Auteur ; Imogen SKELTON, Auteur ; Wickliffe C. ABRAHAM, Auteur ; Yi-Ping HSUEH, Auteur ; Johanna M. MONTGOMERY, Auteur Article en page(s) : 13 p. Langues : Anglais (eng) Mots-clés : Animals Autism Spectrum Disorder/genetics Dietary Supplements Disease Models, Animal Fear/physiology Humans Mice Microfilament Proteins/metabolism Nerve Tissue Proteins/genetics Receptors, N-Methyl-D-Aspartate Synapses/metabolism T-Box Domain Proteins/metabolism/pharmacology Zinc/metabolism/pharmacology Amygdala Autism spectrum disorder Dietary zinc supplementation Glutamatergic synapses N-methyl-D-aspartate receptors T-brain-1 Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterised by a dyad of behavioural symptoms-social and communication deficits and repetitive behaviours. Multiple aetiological genetic and environmental factors have been identified as causing or increasing the likelihood of ASD, including serum zinc deficiency. Our previous studies revealed that dietary zinc supplementation can normalise impaired social behaviours, excessive grooming, and heightened anxiety in a Shank3 mouse model of ASD, as well as the amelioration of synapse dysfunction. Here, we have examined the efficacy and breadth of dietary zinc supplementation as an effective therapeutic strategy utilising a non-Shank-related mouse model of ASD-mice with Tbr1 haploinsufficiency. METHODS: We performed behavioural assays, amygdalar slice whole-cell patch-clamp electrophysiology, and immunohistochemistry to characterise the synaptic mechanisms underlying the ASD-associated behavioural deficits observed in Tbr1(+/-) mice and the therapeutic potential of dietary zinc supplementation. Two-way analysis of variance (ANOVA) with ?ídák's post hoc test and one-way ANOVA with Tukey's post hoc multiple comparisons were performed for statistical analysis. RESULTS: Our data show that dietary zinc supplementation prevents impairments in auditory fear memory and social interaction, but not social novelty, in the Tbr1(+/-) mice. Tbr1 haploinsufficiency did not induce excessive grooming nor elevate anxiety in mice. At the synaptic level, dietary zinc supplementation reversed ?-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) and N-methyl-D-aspartate receptor (NMDAR) hypofunction and normalised presynaptic function at thalamic-lateral amygdala (LA) synapses that are crucial for auditory fear memory. In addition, the zinc supplemented diet significantly restored the synaptic puncta density of the GluN1 subunit essential for functional NMDARs as well as SHANK3 expression in both the basal and lateral amygdala (BLA) of Tbr1(+/-) mice. LIMITATIONS: The therapeutic effect of dietary zinc supplementation observed in rodent models may not reproduce the same effects in human patients. The effect of dietary zinc supplementation on synaptic function in other brain structures affected by Tbr1 haploinsufficiency including olfactory bulb and anterior commissure will also need to be examined. CONCLUSIONS: Our data further the understanding of the molecular mechanisms underlying the effect of dietary zinc supplementation and verify the efficacy and breadth of its application as a potential treatment strategy for ASD. En ligne : http://dx.doi.org/10.1186/s13229-022-00494-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=477
in Molecular Autism > 13 (2022) . - 13 p.[article] Dietary zinc supplementation rescues fear-based learning and synaptic function in the Tbr1(+/-) mouse model of autism spectrum disorders [Texte imprimé et/ou numérique] / Kevin LEE, Auteur ; Yewon JUNG, Auteur ; Yukti VYAS, Auteur ; Imogen SKELTON, Auteur ; Wickliffe C. ABRAHAM, Auteur ; Yi-Ping HSUEH, Auteur ; Johanna M. MONTGOMERY, Auteur . - 13 p.
Langues : Anglais (eng)
in Molecular Autism > 13 (2022) . - 13 p.
Mots-clés : Animals Autism Spectrum Disorder/genetics Dietary Supplements Disease Models, Animal Fear/physiology Humans Mice Microfilament Proteins/metabolism Nerve Tissue Proteins/genetics Receptors, N-Methyl-D-Aspartate Synapses/metabolism T-Box Domain Proteins/metabolism/pharmacology Zinc/metabolism/pharmacology Amygdala Autism spectrum disorder Dietary zinc supplementation Glutamatergic synapses N-methyl-D-aspartate receptors T-brain-1 Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterised by a dyad of behavioural symptoms-social and communication deficits and repetitive behaviours. Multiple aetiological genetic and environmental factors have been identified as causing or increasing the likelihood of ASD, including serum zinc deficiency. Our previous studies revealed that dietary zinc supplementation can normalise impaired social behaviours, excessive grooming, and heightened anxiety in a Shank3 mouse model of ASD, as well as the amelioration of synapse dysfunction. Here, we have examined the efficacy and breadth of dietary zinc supplementation as an effective therapeutic strategy utilising a non-Shank-related mouse model of ASD-mice with Tbr1 haploinsufficiency. METHODS: We performed behavioural assays, amygdalar slice whole-cell patch-clamp electrophysiology, and immunohistochemistry to characterise the synaptic mechanisms underlying the ASD-associated behavioural deficits observed in Tbr1(+/-) mice and the therapeutic potential of dietary zinc supplementation. Two-way analysis of variance (ANOVA) with ?ídák's post hoc test and one-way ANOVA with Tukey's post hoc multiple comparisons were performed for statistical analysis. RESULTS: Our data show that dietary zinc supplementation prevents impairments in auditory fear memory and social interaction, but not social novelty, in the Tbr1(+/-) mice. Tbr1 haploinsufficiency did not induce excessive grooming nor elevate anxiety in mice. At the synaptic level, dietary zinc supplementation reversed ?-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) and N-methyl-D-aspartate receptor (NMDAR) hypofunction and normalised presynaptic function at thalamic-lateral amygdala (LA) synapses that are crucial for auditory fear memory. In addition, the zinc supplemented diet significantly restored the synaptic puncta density of the GluN1 subunit essential for functional NMDARs as well as SHANK3 expression in both the basal and lateral amygdala (BLA) of Tbr1(+/-) mice. LIMITATIONS: The therapeutic effect of dietary zinc supplementation observed in rodent models may not reproduce the same effects in human patients. The effect of dietary zinc supplementation on synaptic function in other brain structures affected by Tbr1 haploinsufficiency including olfactory bulb and anterior commissure will also need to be examined. CONCLUSIONS: Our data further the understanding of the molecular mechanisms underlying the effect of dietary zinc supplementation and verify the efficacy and breadth of its application as a potential treatment strategy for ASD. En ligne : http://dx.doi.org/10.1186/s13229-022-00494-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=477 The relevance of the interpersonal theory of suicide for predicting past-year and lifetime suicidality in autistic adults / R. L. MOSELEY in Molecular Autism, 13 (2022)
![]()
[article]
Titre : The relevance of the interpersonal theory of suicide for predicting past-year and lifetime suicidality in autistic adults Type de document : Texte imprimé et/ou numérique Auteurs : R. L. MOSELEY, Auteur ; N. J. GREGORY, Auteur ; P. SMITH, Auteur ; C. ALLISON, Auteur ; S. CASSIDY, Auteur ; Simon BARON-COHEN, Auteur Article en page(s) : 14 p. Langues : Anglais (eng) Mots-clés : Adult Autistic Disorder Cross-Sectional Studies Humans Interpersonal Relations Phobic Disorders Prospective Studies Psychological Theory Risk Factors Suicide Acquired capability Age at diagnosis Index. décimale : PER Périodiques Résumé : BACKGROUND: While there are known risk factors for suicidality in autistic adults, these are often unconnected from theoretical frameworks that might explain why risk is elevated and guide clinical interventions. The present study investigated the relevance of constructs from the Interpersonal Theory of Suicide (ITS), including perceived burdensomeness, thwarted belongingness and acquired capability for suicide, and explored mechanisms through which certain risk factors (relationship status, age at diagnosis) might elevate suicide risk. METHODS: Autistic adults (n=314) completed an online study including measures of depression, anxiety and constructs from the ITS. Linear and multinomial regression analysis disentangled contributions of ITS variables from effects of depression and anxiety for past-year suicide ideation, past-year and lifetime suicide attempts. Mediation analyses examined associations between risk factors and these suicide outcomes via mechanisms proposed by the ITS. RESULTS: Past-year suicide ideation was associated with burdensomeness, mental rehearsal of suicide plans (a facet of acquired capability), and depression. Greater feelings of burdensomeness, and reduced fear of death, marked out participants who had attempted suicide in comparison to those who had experienced suicide ideation in the past year. Relationship status was indirectly associated with past-year suicide ideation via the mediators of depression and burdensomeness, and was associated with past-year attempts via its effect on ideation. Age at diagnosis was unrelated to any variables. LIMITATIONS: Cross-sectional research is insensitive to causality and temporal dynamics, which is likely why interaction hypotheses from the ITS were unsupported. Normative measures may be invalid in autistic samples. There was no control group. The autistic sample was unrepresentative of the whole population, particularly autistic people with intellectual disabilities, ethnic/racial minorities, and gender minorities. CONCLUSIONS: Perceived burdensomeness and acquired capability appear potentially important to suicide in autistic people, and may mediate the effects of some risk factors. Future research should explore the temporal dynamics of suicide trajectories in longitudinal, prospective designs. En ligne : http://dx.doi.org/10.1186/s13229-022-00495-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=477
in Molecular Autism > 13 (2022) . - 14 p.[article] The relevance of the interpersonal theory of suicide for predicting past-year and lifetime suicidality in autistic adults [Texte imprimé et/ou numérique] / R. L. MOSELEY, Auteur ; N. J. GREGORY, Auteur ; P. SMITH, Auteur ; C. ALLISON, Auteur ; S. CASSIDY, Auteur ; Simon BARON-COHEN, Auteur . - 14 p.
Langues : Anglais (eng)
in Molecular Autism > 13 (2022) . - 14 p.
Mots-clés : Adult Autistic Disorder Cross-Sectional Studies Humans Interpersonal Relations Phobic Disorders Prospective Studies Psychological Theory Risk Factors Suicide Acquired capability Age at diagnosis Index. décimale : PER Périodiques Résumé : BACKGROUND: While there are known risk factors for suicidality in autistic adults, these are often unconnected from theoretical frameworks that might explain why risk is elevated and guide clinical interventions. The present study investigated the relevance of constructs from the Interpersonal Theory of Suicide (ITS), including perceived burdensomeness, thwarted belongingness and acquired capability for suicide, and explored mechanisms through which certain risk factors (relationship status, age at diagnosis) might elevate suicide risk. METHODS: Autistic adults (n=314) completed an online study including measures of depression, anxiety and constructs from the ITS. Linear and multinomial regression analysis disentangled contributions of ITS variables from effects of depression and anxiety for past-year suicide ideation, past-year and lifetime suicide attempts. Mediation analyses examined associations between risk factors and these suicide outcomes via mechanisms proposed by the ITS. RESULTS: Past-year suicide ideation was associated with burdensomeness, mental rehearsal of suicide plans (a facet of acquired capability), and depression. Greater feelings of burdensomeness, and reduced fear of death, marked out participants who had attempted suicide in comparison to those who had experienced suicide ideation in the past year. Relationship status was indirectly associated with past-year suicide ideation via the mediators of depression and burdensomeness, and was associated with past-year attempts via its effect on ideation. Age at diagnosis was unrelated to any variables. LIMITATIONS: Cross-sectional research is insensitive to causality and temporal dynamics, which is likely why interaction hypotheses from the ITS were unsupported. Normative measures may be invalid in autistic samples. There was no control group. The autistic sample was unrepresentative of the whole population, particularly autistic people with intellectual disabilities, ethnic/racial minorities, and gender minorities. CONCLUSIONS: Perceived burdensomeness and acquired capability appear potentially important to suicide in autistic people, and may mediate the effects of some risk factors. Future research should explore the temporal dynamics of suicide trajectories in longitudinal, prospective designs. En ligne : http://dx.doi.org/10.1186/s13229-022-00495-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=477 The autism biomarkers consortium for clinical trials: evaluation of a battery of candidate eye-tracking biomarkers for use in autism clinical trials / Frederick SHIC in Molecular Autism, 13 (2022)
![]()
[article]
Titre : The autism biomarkers consortium for clinical trials: evaluation of a battery of candidate eye-tracking biomarkers for use in autism clinical trials Type de document : Texte imprimé et/ou numérique Auteurs : Frederick SHIC, Auteur ; Adam J. NAPLES, Auteur ; Erin C. BARNEY, Auteur ; Shou An CHANG, Auteur ; Beibin LI, Auteur ; Takumi MCALLISTER, Auteur ; Minah KIM, Auteur ; Kelsey J. DOMMER, Auteur ; Simone HASSELMO, Auteur ; Adham ATYABI, Auteur ; Quan WANG, Auteur ; Gerhard HELLEMAN, Auteur ; April R. LEVIN, Auteur ; Helen SEOW, Auteur ; Raphael BERNIER, Auteur ; Katarzyna CHARWASKA, Auteur ; Geraldine DAWSON, Auteur ; James DZIURA, Auteur ; Susan FAJA, Auteur ; Shafali SPURLING JESTE, Auteur ; Scott P. JOHNSON, Auteur ; Michael MURIAS, Auteur ; Charles A. NELSON, Auteur ; Maura SABATOS-DEVITO, Auteur ; Damla SENTURK, Auteur ; Catherine A. SUGAR, Auteur ; Sara J. WEBB, Auteur ; James C. MCPARTLAND, Auteur Article en page(s) : 15 p. Langues : Anglais (eng) Mots-clés : Autism Spectrum Disorder/diagnosis/psychology Autistic Disorder/diagnosis Biomarkers Child Eye Movements Eye-Tracking Technology Humans Autism spectrum disorder Biological motion Eye tracking Face processing Gaze pattern Visual attention Index. décimale : PER Périodiques Résumé : BACKGROUND: Eye tracking (ET) is a powerful methodology for studying attentional processes through quantification of eye movements. The precision, usability, and cost-effectiveness of ET render it a promising platform for developing biomarkers for use in clinical trials for autism spectrum disorder (ASD). METHODS: The autism biomarkers consortium for clinical trials conducted a multisite, observational study of 6-11-year-old children with ASD (n=280) and typical development (TD, n=119). The ET battery included: Activity Monitoring, Social Interactive, Static Social Scenes, Biological Motion Preference, and Pupillary Light Reflex tasks. A priori, gaze to faces in Activity Monitoring, Social Interactive, and Static Social Scenes tasks were aggregated into an Oculomotor Index of Gaze to Human Faces (OMI) as the primary outcome measure. This work reports on fundamental biomarker properties (data acquisition rates, construct validity, six-week stability, group discrimination, and clinical relationships) derived from these assays that serve as a base for subsequent development of clinical trial biomarker applications. RESULTS: All tasks exhibited excellent acquisition rates, met expectations for construct validity, had moderate or high six-week stabilities, and highlighted subsets of the ASD group with distinct biomarker performance. Within ASD, higher OMI was associated with increased memory for faces, decreased autism symptom severity, and higher verbal IQ and pragmatic communication skills. LIMITATIONS: No specific interventions were administered in this study, limiting information about how ET biomarkers track or predict outcomes in response to treatment. This study did not consider co-occurrence of psychiatric conditions nor specificity in comparison with non-ASD special populations, therefore limiting our understanding of the applicability of outcomes to specific clinical contexts-of-use. Research-grade protocols and equipment were used; further studies are needed to explore deployment in less standardized contexts. CONCLUSIONS: All ET tasks met expectations regarding biomarker properties, with strongest performance for tasks associated with attention to human faces and weakest performance associated with biological motion preference. Based on these data, the OMI has been accepted to the FDA's Biomarker Qualification program, providing a path for advancing efforts to develop biomarkers for use in clinical trials. En ligne : http://dx.doi.org/10.1186/s13229-021-00482-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=477
in Molecular Autism > 13 (2022) . - 15 p.[article] The autism biomarkers consortium for clinical trials: evaluation of a battery of candidate eye-tracking biomarkers for use in autism clinical trials [Texte imprimé et/ou numérique] / Frederick SHIC, Auteur ; Adam J. NAPLES, Auteur ; Erin C. BARNEY, Auteur ; Shou An CHANG, Auteur ; Beibin LI, Auteur ; Takumi MCALLISTER, Auteur ; Minah KIM, Auteur ; Kelsey J. DOMMER, Auteur ; Simone HASSELMO, Auteur ; Adham ATYABI, Auteur ; Quan WANG, Auteur ; Gerhard HELLEMAN, Auteur ; April R. LEVIN, Auteur ; Helen SEOW, Auteur ; Raphael BERNIER, Auteur ; Katarzyna CHARWASKA, Auteur ; Geraldine DAWSON, Auteur ; James DZIURA, Auteur ; Susan FAJA, Auteur ; Shafali SPURLING JESTE, Auteur ; Scott P. JOHNSON, Auteur ; Michael MURIAS, Auteur ; Charles A. NELSON, Auteur ; Maura SABATOS-DEVITO, Auteur ; Damla SENTURK, Auteur ; Catherine A. SUGAR, Auteur ; Sara J. WEBB, Auteur ; James C. MCPARTLAND, Auteur . - 15 p.
Langues : Anglais (eng)
in Molecular Autism > 13 (2022) . - 15 p.
Mots-clés : Autism Spectrum Disorder/diagnosis/psychology Autistic Disorder/diagnosis Biomarkers Child Eye Movements Eye-Tracking Technology Humans Autism spectrum disorder Biological motion Eye tracking Face processing Gaze pattern Visual attention Index. décimale : PER Périodiques Résumé : BACKGROUND: Eye tracking (ET) is a powerful methodology for studying attentional processes through quantification of eye movements. The precision, usability, and cost-effectiveness of ET render it a promising platform for developing biomarkers for use in clinical trials for autism spectrum disorder (ASD). METHODS: The autism biomarkers consortium for clinical trials conducted a multisite, observational study of 6-11-year-old children with ASD (n=280) and typical development (TD, n=119). The ET battery included: Activity Monitoring, Social Interactive, Static Social Scenes, Biological Motion Preference, and Pupillary Light Reflex tasks. A priori, gaze to faces in Activity Monitoring, Social Interactive, and Static Social Scenes tasks were aggregated into an Oculomotor Index of Gaze to Human Faces (OMI) as the primary outcome measure. This work reports on fundamental biomarker properties (data acquisition rates, construct validity, six-week stability, group discrimination, and clinical relationships) derived from these assays that serve as a base for subsequent development of clinical trial biomarker applications. RESULTS: All tasks exhibited excellent acquisition rates, met expectations for construct validity, had moderate or high six-week stabilities, and highlighted subsets of the ASD group with distinct biomarker performance. Within ASD, higher OMI was associated with increased memory for faces, decreased autism symptom severity, and higher verbal IQ and pragmatic communication skills. LIMITATIONS: No specific interventions were administered in this study, limiting information about how ET biomarkers track or predict outcomes in response to treatment. This study did not consider co-occurrence of psychiatric conditions nor specificity in comparison with non-ASD special populations, therefore limiting our understanding of the applicability of outcomes to specific clinical contexts-of-use. Research-grade protocols and equipment were used; further studies are needed to explore deployment in less standardized contexts. CONCLUSIONS: All ET tasks met expectations regarding biomarker properties, with strongest performance for tasks associated with attention to human faces and weakest performance associated with biological motion preference. Based on these data, the OMI has been accepted to the FDA's Biomarker Qualification program, providing a path for advancing efforts to develop biomarkers for use in clinical trials. En ligne : http://dx.doi.org/10.1186/s13229-021-00482-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=477 Correction to: The relevance of the interpersonal theory of suicide for predicting past-year and lifetime suicidality in autistic adults / R. L. MOSELEY in Molecular Autism, 13 (2022)
![]()
[article]
Titre : Correction to: The relevance of the interpersonal theory of suicide for predicting past-year and lifetime suicidality in autistic adults Type de document : Texte imprimé et/ou numérique Auteurs : R. L. MOSELEY, Auteur ; N. J. GREGORY, Auteur ; P. SMITH, Auteur ; C. ALLISON, Auteur ; S. CASSIDY, Auteur ; Simon BARON-COHEN, Auteur Article en page(s) : 16 p. Langues : Anglais (eng) Index. décimale : PER Périodiques En ligne : http://dx.doi.org/10.1186/s13229-022-00496-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=477
in Molecular Autism > 13 (2022) . - 16 p.[article] Correction to: The relevance of the interpersonal theory of suicide for predicting past-year and lifetime suicidality in autistic adults [Texte imprimé et/ou numérique] / R. L. MOSELEY, Auteur ; N. J. GREGORY, Auteur ; P. SMITH, Auteur ; C. ALLISON, Auteur ; S. CASSIDY, Auteur ; Simon BARON-COHEN, Auteur . - 16 p.
Langues : Anglais (eng)
in Molecular Autism > 13 (2022) . - 16 p.
Index. décimale : PER Périodiques En ligne : http://dx.doi.org/10.1186/s13229-022-00496-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=477 Clinical trial of insulin-like growth factor-1 in Phelan-McDermid syndrome / A. KOLEVZON in Molecular Autism, 13 (2022)
![]()
[article]
Titre : Clinical trial of insulin-like growth factor-1 in Phelan-McDermid syndrome Type de document : Texte imprimé et/ou numérique Auteurs : A. KOLEVZON, Auteur ; M. S. BREEN, Auteur ; P. M. SIPER, Auteur ; Danielle B. HALPERN, Auteur ; Y. FRANK, Auteur ; H. RIEGER, Auteur ; J. WEISMANN, Auteur ; M. P. TRELLES, Auteur ; B. LERMAN, Auteur ; R. RAPAPORT, Auteur ; J. D. BUXBAUM, Auteur Article en page(s) : 17 p. Langues : Anglais (eng) Mots-clés : Child Chromosome Deletion Chromosome Disorders/drug therapy/genetics Chromosomes, Human, Pair 22 Humans Insulin-Like Growth Factor I/therapeutic use Pilot Projects Asd Autism spectrum disorder Igf-1 Insulin-like growth factor-1 Pms Phelan-McDermid syndrome shank3 Index. décimale : PER Périodiques Résumé : BACKGROUND: Phelan-McDermid syndrome (PMS) is caused by haploinsufficiency of the SHANK3 gene and is characterized by global developmental delays and autism spectrum disorder (ASD). Based on several converging lines of preclinical and clinical evidence supporting the use of insulin-like growth factor-1 (IGF-1) in PMS, this study aims to follow-up a previous pilot study with IGF-1 to further evaluate this novel therapeutic for core symptoms of ASD in children with PMS. METHODS: Ten children aged 5-9 with PMS were enrolled. Participants were randomized to receive IGF-1 or placebo (saline) using a 12-week, double-blind, crossover design. Efficacy was assessed using the primary outcome of the Aberrant Behavior Checklist-Social Withdrawal (ABC-SW) subscale as well as secondary outcome measures reflecting core symptoms of ASD. To increase power and sample size, we jointly analyzed the effect of IGF-1 reported here together with results from our previous controlled trail of IGF-1 in children with PMS (combined N=19). RESULTS: Results on the ABC-SW did not reach statistical significance, however significant improvements in sensory reactivity symptoms were observed. In our pooled analyses, IGF-1 treatment also led to significant improvements in repetitive behaviors and hyperactivity. There were no other statistically significant effects seen across other clinical outcome measures. IGF-1 was well tolerated and there were no serious adverse events. LIMITATIONS: The small sample size and expectancy bias due to relying on parent reported outcome measures may contribute to limitations in interpreting results. CONCLUSION: IGF-1 is efficacious in improving sensory reactivity symptoms, repetitive behaviors, and hyperactivity in children with PMS. Trial registration NCT01525901. En ligne : http://dx.doi.org/10.1186/s13229-022-00493-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=477
in Molecular Autism > 13 (2022) . - 17 p.[article] Clinical trial of insulin-like growth factor-1 in Phelan-McDermid syndrome [Texte imprimé et/ou numérique] / A. KOLEVZON, Auteur ; M. S. BREEN, Auteur ; P. M. SIPER, Auteur ; Danielle B. HALPERN, Auteur ; Y. FRANK, Auteur ; H. RIEGER, Auteur ; J. WEISMANN, Auteur ; M. P. TRELLES, Auteur ; B. LERMAN, Auteur ; R. RAPAPORT, Auteur ; J. D. BUXBAUM, Auteur . - 17 p.
Langues : Anglais (eng)
in Molecular Autism > 13 (2022) . - 17 p.
Mots-clés : Child Chromosome Deletion Chromosome Disorders/drug therapy/genetics Chromosomes, Human, Pair 22 Humans Insulin-Like Growth Factor I/therapeutic use Pilot Projects Asd Autism spectrum disorder Igf-1 Insulin-like growth factor-1 Pms Phelan-McDermid syndrome shank3 Index. décimale : PER Périodiques Résumé : BACKGROUND: Phelan-McDermid syndrome (PMS) is caused by haploinsufficiency of the SHANK3 gene and is characterized by global developmental delays and autism spectrum disorder (ASD). Based on several converging lines of preclinical and clinical evidence supporting the use of insulin-like growth factor-1 (IGF-1) in PMS, this study aims to follow-up a previous pilot study with IGF-1 to further evaluate this novel therapeutic for core symptoms of ASD in children with PMS. METHODS: Ten children aged 5-9 with PMS were enrolled. Participants were randomized to receive IGF-1 or placebo (saline) using a 12-week, double-blind, crossover design. Efficacy was assessed using the primary outcome of the Aberrant Behavior Checklist-Social Withdrawal (ABC-SW) subscale as well as secondary outcome measures reflecting core symptoms of ASD. To increase power and sample size, we jointly analyzed the effect of IGF-1 reported here together with results from our previous controlled trail of IGF-1 in children with PMS (combined N=19). RESULTS: Results on the ABC-SW did not reach statistical significance, however significant improvements in sensory reactivity symptoms were observed. In our pooled analyses, IGF-1 treatment also led to significant improvements in repetitive behaviors and hyperactivity. There were no other statistically significant effects seen across other clinical outcome measures. IGF-1 was well tolerated and there were no serious adverse events. LIMITATIONS: The small sample size and expectancy bias due to relying on parent reported outcome measures may contribute to limitations in interpreting results. CONCLUSION: IGF-1 is efficacious in improving sensory reactivity symptoms, repetitive behaviors, and hyperactivity in children with PMS. Trial registration NCT01525901. En ligne : http://dx.doi.org/10.1186/s13229-022-00493-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=477 A constellation of eye-tracking measures reveals social attention differences in ASD and the broad autism phenotype / Kritika NAYAR in Molecular Autism, 13 (2022)
![]()
[article]
Titre : A constellation of eye-tracking measures reveals social attention differences in ASD and the broad autism phenotype Type de document : Texte imprimé et/ou numérique Auteurs : Kritika NAYAR, Auteur ; Frederick SHIC, Auteur ; Molly WINSTON, Auteur ; Molly LOSH, Auteur Article en page(s) : 18 p. Langues : Anglais (eng) Mots-clés : Attention Autism Spectrum Disorder/diagnosis Autistic Disorder Eye-Tracking Technology Fixation, Ocular Humans Phenotype Autism spectrum disorder Broad autism phenotype Endophenotype Eye tracking Social attention Visual processing Index. décimale : PER Périodiques Résumé : BACKGROUND: Social attention differences, expressed through gaze patterns, have been documented in autism spectrum disorder (ASD), with subtle differences also reported among first-degree relatives, suggesting a shared genetic link. Findings have mostly been derived from standard eye-tracking methods (total fixation count or total fixation duration). Given the dynamics of visual attention, these standard methods may obscure subtle, yet core, differences in visual attention mechanisms, particularly those presenting sub-clinically. This study applied a constellation of eye-tracking analyses to gaze data from individuals with ASD and their parents. METHODS: This study included n=156 participants across groups, including ASD (n=24) and control (n=32) groups, and parents of individuals with ASD (n=61) and control parents (n=39). A complex scene with social/non-social elements was displayed and gaze tracked via an eye tracker. Eleven analytic methods from the following categories were analyzed: (1) standard variables, (2) temporal dynamics (e.g., gaze over time), (3) fixation patterns (e.g., perseverative or regressive fixations), (4) first fixations, and (5) distribution patterns. MANOVAs, growth curve analyses, and Chi-squared tests were applied to examine group differences. Finally, group differences were examined on component scores derived from a principal component analysis (PCA) that reduced variables to distinct dimensions. RESULTS: No group differences emerged among standard, first fixation, and distribution pattern variables. Both the ASD and ASD parent groups demonstrated on average reduced social attention over time and atypical perseverative fixations. Lower social attention factor scores derived from PCA strongly differentiated the ASD and ASD parent groups from controls, with parent findings driven by the subset of parents demonstrating the broad autism phenotype. LIMITATIONS: To generalize these findings, larger sample sizes, extended viewing contexts (e.g., dynamic stimuli), and even more eye-tracking analytical methods are needed. CONCLUSIONS: Fixations over time and perseverative fixations differentiated ASD and the ASD parent groups from controls, with the PCA most robustly capturing social attention differences. Findings highlight their methodological utility in studies of the (broad) autism spectrum to capture nuanced visual attention differences that may relate to clinical symptoms in ASD, and reflect genetic liability in clinically unaffected relatives. This proof-of-concept study may inform future studies using eye tracking across populations where social attention is impacted. En ligne : http://dx.doi.org/10.1186/s13229-022-00490-w Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=477
in Molecular Autism > 13 (2022) . - 18 p.[article] A constellation of eye-tracking measures reveals social attention differences in ASD and the broad autism phenotype [Texte imprimé et/ou numérique] / Kritika NAYAR, Auteur ; Frederick SHIC, Auteur ; Molly WINSTON, Auteur ; Molly LOSH, Auteur . - 18 p.
Langues : Anglais (eng)
in Molecular Autism > 13 (2022) . - 18 p.
Mots-clés : Attention Autism Spectrum Disorder/diagnosis Autistic Disorder Eye-Tracking Technology Fixation, Ocular Humans Phenotype Autism spectrum disorder Broad autism phenotype Endophenotype Eye tracking Social attention Visual processing Index. décimale : PER Périodiques Résumé : BACKGROUND: Social attention differences, expressed through gaze patterns, have been documented in autism spectrum disorder (ASD), with subtle differences also reported among first-degree relatives, suggesting a shared genetic link. Findings have mostly been derived from standard eye-tracking methods (total fixation count or total fixation duration). Given the dynamics of visual attention, these standard methods may obscure subtle, yet core, differences in visual attention mechanisms, particularly those presenting sub-clinically. This study applied a constellation of eye-tracking analyses to gaze data from individuals with ASD and their parents. METHODS: This study included n=156 participants across groups, including ASD (n=24) and control (n=32) groups, and parents of individuals with ASD (n=61) and control parents (n=39). A complex scene with social/non-social elements was displayed and gaze tracked via an eye tracker. Eleven analytic methods from the following categories were analyzed: (1) standard variables, (2) temporal dynamics (e.g., gaze over time), (3) fixation patterns (e.g., perseverative or regressive fixations), (4) first fixations, and (5) distribution patterns. MANOVAs, growth curve analyses, and Chi-squared tests were applied to examine group differences. Finally, group differences were examined on component scores derived from a principal component analysis (PCA) that reduced variables to distinct dimensions. RESULTS: No group differences emerged among standard, first fixation, and distribution pattern variables. Both the ASD and ASD parent groups demonstrated on average reduced social attention over time and atypical perseverative fixations. Lower social attention factor scores derived from PCA strongly differentiated the ASD and ASD parent groups from controls, with parent findings driven by the subset of parents demonstrating the broad autism phenotype. LIMITATIONS: To generalize these findings, larger sample sizes, extended viewing contexts (e.g., dynamic stimuli), and even more eye-tracking analytical methods are needed. CONCLUSIONS: Fixations over time and perseverative fixations differentiated ASD and the ASD parent groups from controls, with the PCA most robustly capturing social attention differences. Findings highlight their methodological utility in studies of the (broad) autism spectrum to capture nuanced visual attention differences that may relate to clinical symptoms in ASD, and reflect genetic liability in clinically unaffected relatives. This proof-of-concept study may inform future studies using eye tracking across populations where social attention is impacted. En ligne : http://dx.doi.org/10.1186/s13229-022-00490-w Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=477 Myt1l haploinsufficiency leads to obesity and multifaceted behavioral alterations in mice / Markus WÖHR in Molecular Autism, 13 (2022)
![]()
[article]
Titre : Myt1l haploinsufficiency leads to obesity and multifaceted behavioral alterations in mice Type de document : Texte imprimé et/ou numérique Auteurs : Markus WÖHR, Auteur ; Wendy M. FONG, Auteur ; Justyna A. JANAS, Auteur ; Moritz MALL, Auteur ; Christian THOME, Auteur ; Madhuri VANGIPURAM, Auteur ; Lingjun MENG, Auteur ; Thomas C. SÜDHOF, Auteur ; Marius WERNIG, Auteur Article en page(s) : 19 p. Langues : Anglais (eng) Mots-clés : Animals Autism Spectrum Disorder/genetics Behavior, Animal/physiology Haploinsufficiency Mice Nerve Tissue Proteins/genetics Obesity Transcription Factors/genetics Autism Social behavior Transcription factor Ultrasonic vocalization Index. décimale : PER Périodiques Résumé : BACKGROUND: The zinc finger domain containing transcription factor Myt1l is tightly associated with neuronal identity and is the only transcription factor known that is both neuron-specific and expressed in all neuronal subtypes. We identified Myt1l as a powerful reprogramming factor that, in combination with the proneural bHLH factor Ascl1, could induce neuronal fate in fibroblasts. Molecularly, we found it to repress many non-neuronal gene programs, explaining its supportive role to induce and safeguard neuronal identity in combination with proneural bHLH transcriptional activators. Moreover, human genetics studies found MYT1L mutations to cause intellectual disability and autism spectrum disorder often coupled with obesity. METHODS: Here, we generated and characterized Myt1l-deficient mice. A comprehensive, longitudinal behavioral phenotyping approach was applied. RESULTS: Myt1l was necessary for survival beyond 24 h but not for overall histological brain organization. Myt1l heterozygous mice became increasingly overweight and exhibited multifaceted behavioral alterations. In mouse pups, Myt1l haploinsufficiency caused mild alterations in early socio-affective communication through ultrasonic vocalizations. In adulthood, Myt1l heterozygous mice displayed hyperactivity due to impaired habituation learning. Motor performance was reduced in Myt1l heterozygous mice despite intact motor learning, possibly due to muscular hypotonia. While anxiety-related behavior was reduced, acoustic startle reactivity was enhanced, in line with higher sensitivity to loud sound. Finally, Myt1l haploinsufficiency had a negative impact on contextual fear memory retrieval, while cued fear memory retrieval appeared to be intact. LIMITATIONS: In future studies, additional phenotypes might be identified and a detailed characterization of direct reciprocal social interaction behavior might help to reveal effects of Myt1l haploinsufficiency on social behavior in juvenile and adult mice. CONCLUSIONS: Behavioral alterations in Myt1l haploinsufficient mice recapitulate several clinical phenotypes observed in humans carrying heterozygous MYT1L mutations and thus serve as an informative model of the human MYT1L syndrome. En ligne : http://dx.doi.org/10.1186/s13229-022-00497-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=477
in Molecular Autism > 13 (2022) . - 19 p.[article] Myt1l haploinsufficiency leads to obesity and multifaceted behavioral alterations in mice [Texte imprimé et/ou numérique] / Markus WÖHR, Auteur ; Wendy M. FONG, Auteur ; Justyna A. JANAS, Auteur ; Moritz MALL, Auteur ; Christian THOME, Auteur ; Madhuri VANGIPURAM, Auteur ; Lingjun MENG, Auteur ; Thomas C. SÜDHOF, Auteur ; Marius WERNIG, Auteur . - 19 p.
Langues : Anglais (eng)
in Molecular Autism > 13 (2022) . - 19 p.
Mots-clés : Animals Autism Spectrum Disorder/genetics Behavior, Animal/physiology Haploinsufficiency Mice Nerve Tissue Proteins/genetics Obesity Transcription Factors/genetics Autism Social behavior Transcription factor Ultrasonic vocalization Index. décimale : PER Périodiques Résumé : BACKGROUND: The zinc finger domain containing transcription factor Myt1l is tightly associated with neuronal identity and is the only transcription factor known that is both neuron-specific and expressed in all neuronal subtypes. We identified Myt1l as a powerful reprogramming factor that, in combination with the proneural bHLH factor Ascl1, could induce neuronal fate in fibroblasts. Molecularly, we found it to repress many non-neuronal gene programs, explaining its supportive role to induce and safeguard neuronal identity in combination with proneural bHLH transcriptional activators. Moreover, human genetics studies found MYT1L mutations to cause intellectual disability and autism spectrum disorder often coupled with obesity. METHODS: Here, we generated and characterized Myt1l-deficient mice. A comprehensive, longitudinal behavioral phenotyping approach was applied. RESULTS: Myt1l was necessary for survival beyond 24 h but not for overall histological brain organization. Myt1l heterozygous mice became increasingly overweight and exhibited multifaceted behavioral alterations. In mouse pups, Myt1l haploinsufficiency caused mild alterations in early socio-affective communication through ultrasonic vocalizations. In adulthood, Myt1l heterozygous mice displayed hyperactivity due to impaired habituation learning. Motor performance was reduced in Myt1l heterozygous mice despite intact motor learning, possibly due to muscular hypotonia. While anxiety-related behavior was reduced, acoustic startle reactivity was enhanced, in line with higher sensitivity to loud sound. Finally, Myt1l haploinsufficiency had a negative impact on contextual fear memory retrieval, while cued fear memory retrieval appeared to be intact. LIMITATIONS: In future studies, additional phenotypes might be identified and a detailed characterization of direct reciprocal social interaction behavior might help to reveal effects of Myt1l haploinsufficiency on social behavior in juvenile and adult mice. CONCLUSIONS: Behavioral alterations in Myt1l haploinsufficient mice recapitulate several clinical phenotypes observed in humans carrying heterozygous MYT1L mutations and thus serve as an informative model of the human MYT1L syndrome. En ligne : http://dx.doi.org/10.1186/s13229-022-00497-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=477 Globally elevated excitation-inhibition ratio in children with autism spectrum disorder and below-average intelligence / Viktoriya O. MANYUKHINA in Molecular Autism, 13 (2022)
![]()
[article]
Titre : Globally elevated excitation-inhibition ratio in children with autism spectrum disorder and below-average intelligence Type de document : Texte imprimé et/ou numérique Auteurs : Viktoriya O. MANYUKHINA, Auteur ; Andrey O. PROKOFYEV, Auteur ; Ilia A. GALUTA, Auteur ; Dzerassa E. GOIAEVA, Auteur ; Tatiana S. OBUKHOVA, Auteur ; Justin F. SCHNEIDERMAN, Auteur ; Dmitrii I. ALTUKHOV, Auteur ; Tatiana A. STROGANOVA, Auteur ; Elena V. OREKHOVA, Auteur Article en page(s) : 20 p. Langues : Anglais (eng) Mots-clés : Autism Spectrum Disorder Child Cognition/physiology Humans Intellectual Disability Intelligence Magnetoencephalography Male 1/f power law Autism spectrum disorders (ASDs) Biomarkers Excitation?inhibition balance Power spectrum Index. décimale : PER Périodiques Résumé : BACKGROUND: Altered neuronal excitation-inhibition (E-I) balance is strongly implicated in ASD. However, it is not known whether the direction and degree of changes in the E-I ratio in individuals with ASD correlates with intellectual disability often associated with this developmental disorder. The spectral slope of the aperiodic 1/f activity reflects the E-I balance at the scale of large neuronal populations and may uncover its putative alternations in individuals with ASD with and without intellectual disability. METHODS: Herein, we used magnetoencephalography (MEG) to test whether the 1/f slope would differentiate ASD children with average and below-average (85) IQ. MEG was recorded at rest with eyes open/closed in 49 boys with ASD aged 6-15 years with IQ ranging from 54 to 128, and in 49 age-matched typically developing (TD) boys. The cortical source activity was estimated using the beamformer approach and individual brain models. We then extracted the 1/f slope by fitting a linear function to the log-log-scale power spectra in the high-frequency range. RESULTS: The global 1/f slope averaged over all cortical sources demonstrated high rank-order stability between the two conditions. Consistent with previous research, it was steeper in the eyes-closed than in the eyes-open condition and flattened with age. Regardless of condition, children with ASD and below-average IQ had flatter slopes than either TD or ASD children with average or above-average IQ. These group differences could not be explained by differences in signal-to-noise ratio or periodic (alpha and beta) activity. LIMITATIONS: Further research is needed to find out whether the observed changes in E-I ratios are characteristic of children with below-average IQ of other diagnostic groups. CONCLUSIONS: The atypically flattened spectral slope of aperiodic activity in children with ASD and below-average IQ suggests a shift of the global E-I balance toward hyper-excitation. The spectral slope can provide an accessible noninvasive biomarker of the E-I ratio for making objective judgments about treatment effectiveness in people with ASD and comorbid intellectual disability. En ligne : http://dx.doi.org/10.1186/s13229-022-00498-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=477
in Molecular Autism > 13 (2022) . - 20 p.[article] Globally elevated excitation-inhibition ratio in children with autism spectrum disorder and below-average intelligence [Texte imprimé et/ou numérique] / Viktoriya O. MANYUKHINA, Auteur ; Andrey O. PROKOFYEV, Auteur ; Ilia A. GALUTA, Auteur ; Dzerassa E. GOIAEVA, Auteur ; Tatiana S. OBUKHOVA, Auteur ; Justin F. SCHNEIDERMAN, Auteur ; Dmitrii I. ALTUKHOV, Auteur ; Tatiana A. STROGANOVA, Auteur ; Elena V. OREKHOVA, Auteur . - 20 p.
Langues : Anglais (eng)
in Molecular Autism > 13 (2022) . - 20 p.
Mots-clés : Autism Spectrum Disorder Child Cognition/physiology Humans Intellectual Disability Intelligence Magnetoencephalography Male 1/f power law Autism spectrum disorders (ASDs) Biomarkers Excitation?inhibition balance Power spectrum Index. décimale : PER Périodiques Résumé : BACKGROUND: Altered neuronal excitation-inhibition (E-I) balance is strongly implicated in ASD. However, it is not known whether the direction and degree of changes in the E-I ratio in individuals with ASD correlates with intellectual disability often associated with this developmental disorder. The spectral slope of the aperiodic 1/f activity reflects the E-I balance at the scale of large neuronal populations and may uncover its putative alternations in individuals with ASD with and without intellectual disability. METHODS: Herein, we used magnetoencephalography (MEG) to test whether the 1/f slope would differentiate ASD children with average and below-average (85) IQ. MEG was recorded at rest with eyes open/closed in 49 boys with ASD aged 6-15 years with IQ ranging from 54 to 128, and in 49 age-matched typically developing (TD) boys. The cortical source activity was estimated using the beamformer approach and individual brain models. We then extracted the 1/f slope by fitting a linear function to the log-log-scale power spectra in the high-frequency range. RESULTS: The global 1/f slope averaged over all cortical sources demonstrated high rank-order stability between the two conditions. Consistent with previous research, it was steeper in the eyes-closed than in the eyes-open condition and flattened with age. Regardless of condition, children with ASD and below-average IQ had flatter slopes than either TD or ASD children with average or above-average IQ. These group differences could not be explained by differences in signal-to-noise ratio or periodic (alpha and beta) activity. LIMITATIONS: Further research is needed to find out whether the observed changes in E-I ratios are characteristic of children with below-average IQ of other diagnostic groups. CONCLUSIONS: The atypically flattened spectral slope of aperiodic activity in children with ASD and below-average IQ suggests a shift of the global E-I balance toward hyper-excitation. The spectral slope can provide an accessible noninvasive biomarker of the E-I ratio for making objective judgments about treatment effectiveness in people with ASD and comorbid intellectual disability. En ligne : http://dx.doi.org/10.1186/s13229-022-00498-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=477 Resting state EEG power spectrum and functional connectivity in autism: a cross-sectional analysis / Pilar GARCES in Molecular Autism, 13 (2022)
![]()
[article]
Titre : Resting state EEG power spectrum and functional connectivity in autism: a cross-sectional analysis Type de document : Texte imprimé et/ou numérique Auteurs : Pilar GARCES, Auteur ; Sarah BAUMEISTER, Auteur ; Luke MASON, Auteur ; Christopher H. CHATHAM, Auteur ; Stefan HOLIGA, Auteur ; Juergen DUKART, Auteur ; Emily J. H. JONES, Auteur ; Tobias BANASCHEWSKI, Auteur ; Simon BARON-COHEN, Auteur ; Sven BÖLTE, Auteur ; Jan K. BUITELAAR, Auteur ; Sarah DURSTON, Auteur ; Bob ORANJE, Auteur ; Antonio M. PERSICO, Auteur ; Christian F. BECKMANN, Auteur ; Thomas BOUGERON, Auteur ; Flavio DELL'ACQUA, Auteur ; Christine ECKER, Auteur ; Carolin MOESSNANG, Auteur ; Tony CHARMAN, Auteur ; Julian TILLMANN, Auteur ; Declan G. M. MURPHY, Auteur ; Mark H. JOHNSON, Auteur ; Eva LOTH, Auteur ; Daniel BRANDEIS, Auteur ; Joerg F. HIPP, Auteur Article en page(s) : 22 p. Langues : Anglais (eng) Mots-clés : Adolescent Adult Autism Spectrum Disorder/diagnosis Autistic Disorder Brain/diagnostic imaging Brain Mapping/methods Child Cross-Sectional Studies Electroencephalography/methods Humans Magnetic Resonance Imaging/methods Reproducibility of Results Autism spectrum disorder Eeg Functional connectivity Power spectrum Resting state Index. décimale : PER Périodiques Résumé : BACKGROUND: Understanding the development of the neuronal circuitry underlying autism spectrum disorder (ASD) is critical to shed light into its etiology and for the development of treatment options. Resting state EEG provides a window into spontaneous local and long-range neuronal synchronization and has been investigated in many ASD studies, but results are inconsistent. Unbiased investigation in large and comprehensive samples focusing on replicability is needed. METHODS: We quantified resting state EEG alpha peak metrics, power spectrum (PS, 2-32 Hz) and functional connectivity (FC) in 411 children, adolescents and adults (n=212 ASD, n=199 neurotypicals [NT], all with IQ?>?75). We performed analyses in source-space using individual head models derived from the participants' MRIs. We tested for differences in mean and variance between the ASD and NT groups for both PS and FC using linear mixed effects models accounting for age, sex, IQ and site effects. Then, we used machine learning to assess whether a multivariate combination of EEG features could better separate ASD and NT participants. All analyses were embedded within a train-validation approach (70%-30% split). RESULTS: In the training dataset, we found an interaction between age and group for the reactivity to eye opening (p=.042 uncorrected), and a significant but weak multivariate ASD vs. NT classification performance for PS and FC (sensitivity 0.52-0.62, specificity 0.59-0.73). None of these findings replicated significantly in the validation dataset, although the effect size in the validation dataset overlapped with the prediction interval from the training dataset. LIMITATIONS: The statistical power to detect weak effects-of the magnitude of those found in the training dataset-in the validation dataset is small, and we cannot fully conclude on the reproducibility of the training dataset's effects. CONCLUSIONS: This suggests that PS and FC values in ASD and NT have a strong overlap, and that differences between both groups (in both mean and variance) have, at best, a small effect size. Larger studies would be needed to investigate and replicate such potential effects. En ligne : http://dx.doi.org/10.1186/s13229-022-00500-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=477
in Molecular Autism > 13 (2022) . - 22 p.[article] Resting state EEG power spectrum and functional connectivity in autism: a cross-sectional analysis [Texte imprimé et/ou numérique] / Pilar GARCES, Auteur ; Sarah BAUMEISTER, Auteur ; Luke MASON, Auteur ; Christopher H. CHATHAM, Auteur ; Stefan HOLIGA, Auteur ; Juergen DUKART, Auteur ; Emily J. H. JONES, Auteur ; Tobias BANASCHEWSKI, Auteur ; Simon BARON-COHEN, Auteur ; Sven BÖLTE, Auteur ; Jan K. BUITELAAR, Auteur ; Sarah DURSTON, Auteur ; Bob ORANJE, Auteur ; Antonio M. PERSICO, Auteur ; Christian F. BECKMANN, Auteur ; Thomas BOUGERON, Auteur ; Flavio DELL'ACQUA, Auteur ; Christine ECKER, Auteur ; Carolin MOESSNANG, Auteur ; Tony CHARMAN, Auteur ; Julian TILLMANN, Auteur ; Declan G. M. MURPHY, Auteur ; Mark H. JOHNSON, Auteur ; Eva LOTH, Auteur ; Daniel BRANDEIS, Auteur ; Joerg F. HIPP, Auteur . - 22 p.
Langues : Anglais (eng)
in Molecular Autism > 13 (2022) . - 22 p.
Mots-clés : Adolescent Adult Autism Spectrum Disorder/diagnosis Autistic Disorder Brain/diagnostic imaging Brain Mapping/methods Child Cross-Sectional Studies Electroencephalography/methods Humans Magnetic Resonance Imaging/methods Reproducibility of Results Autism spectrum disorder Eeg Functional connectivity Power spectrum Resting state Index. décimale : PER Périodiques Résumé : BACKGROUND: Understanding the development of the neuronal circuitry underlying autism spectrum disorder (ASD) is critical to shed light into its etiology and for the development of treatment options. Resting state EEG provides a window into spontaneous local and long-range neuronal synchronization and has been investigated in many ASD studies, but results are inconsistent. Unbiased investigation in large and comprehensive samples focusing on replicability is needed. METHODS: We quantified resting state EEG alpha peak metrics, power spectrum (PS, 2-32 Hz) and functional connectivity (FC) in 411 children, adolescents and adults (n=212 ASD, n=199 neurotypicals [NT], all with IQ?>?75). We performed analyses in source-space using individual head models derived from the participants' MRIs. We tested for differences in mean and variance between the ASD and NT groups for both PS and FC using linear mixed effects models accounting for age, sex, IQ and site effects. Then, we used machine learning to assess whether a multivariate combination of EEG features could better separate ASD and NT participants. All analyses were embedded within a train-validation approach (70%-30% split). RESULTS: In the training dataset, we found an interaction between age and group for the reactivity to eye opening (p=.042 uncorrected), and a significant but weak multivariate ASD vs. NT classification performance for PS and FC (sensitivity 0.52-0.62, specificity 0.59-0.73). None of these findings replicated significantly in the validation dataset, although the effect size in the validation dataset overlapped with the prediction interval from the training dataset. LIMITATIONS: The statistical power to detect weak effects-of the magnitude of those found in the training dataset-in the validation dataset is small, and we cannot fully conclude on the reproducibility of the training dataset's effects. CONCLUSIONS: This suggests that PS and FC values in ASD and NT have a strong overlap, and that differences between both groups (in both mean and variance) have, at best, a small effect size. Larger studies would be needed to investigate and replicate such potential effects. En ligne : http://dx.doi.org/10.1186/s13229-022-00500-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=477 White matter microstructural and morphometric alterations in autism: implications for intellectual capabilities / Chun-Hung YEH in Molecular Autism, 13 (2022)
![]()
[article]
Titre : White matter microstructural and morphometric alterations in autism: implications for intellectual capabilities Type de document : Texte imprimé et/ou numérique Auteurs : Chun-Hung YEH, Auteur ; Rung-Yu TSENG, Auteur ; Hsing-Chang NI, Auteur ; Luca COCCHI, Auteur ; Jung-Chi CHANG, Auteur ; Mei-Yun HSU, Auteur ; En-Nien TU, Auteur ; Yu-Yu WU, Auteur ; Tai-Li CHOU, Auteur ; Susan Shur-Fen GAU, Auteur ; Hsiang-Yuan LIN, Auteur Article en page(s) : 21 p. Langues : Anglais (eng) Mots-clés : Adolescent Autism Spectrum Disorder/diagnostic imaging/pathology Autistic Disorder/diagnostic imaging/pathology Brain/diagnostic imaging/pathology Corpus Callosum/diagnostic imaging Diffusion Magnetic Resonance Imaging/methods Humans White Matter/diagnostic imaging/pathology Autism spectrum disorder Cerebellum Diffusion MRI Fixel-based analysis Intellectual disabilities Minimally verbal status Index. décimale : PER Périodiques Résumé : BACKGROUND: Neuroimage literature of autism spectrum disorder (ASD) has a moderate-to-high risk of bias, partially because those combined with intellectual impairment (II) and/or minimally verbal (MV) status are generally ignored. We aimed to provide more comprehensive insights into white matter alterations of ASD, inclusive of individuals with II (ASD-II-Only) or MV expression (ASD-MV). METHODS: Sixty-five participants with ASD (ASD-Whole; 16.6?+?5.9 years; comprising 34 intellectually able youth, ASD-IA, and 31 intellectually impaired youth, ASD-II, including 24 ASD-II-Only plus 7 ASD-MV) and 38 demographic-matched typically developing controls (TDC; 17.3?+?5.6 years) were scanned in accelerated diffusion-weighted MRI. Fixel-based analysis was undertaken to investigate the categorical differences in fiber density (FD), fiber cross section (FC), and a combined index (FDC), and brain symptom/cognition associations. RESULTS: ASD-Whole had reduced FD in the anterior and posterior corpus callosum and left cerebellum Crus I, and smaller FDC in right cerebellum Crus II, compared to TDC. ASD-IA, relative to TDC, had no significant discrepancies, while ASD-II showed almost identical alterations to those from ASD-Whole vs. TDC. ASD-II-Only had greater FD/FDC in the isthmus splenium of callosum than ASD-MV. Autistic severity negatively correlated with FC in right Crus I. Nonverbal full-scale IQ positively correlated with FC/FDC in cerebellum VI. FD/FDC of the right dorsolateral prefrontal cortex showed a diagnosis-by-executive function interaction. LIMITATIONS: We could not preclude the potential effects of age and sex from the ASD cohort, although statistical tests suggested that these factors were not influential. Our results could be confounded by variable psychiatric comorbidities and psychotropic medication uses in our ASD participants recruited from outpatient clinics, which is nevertheless closer to a real-world presentation of ASD. The outcomes related to ASD-MV were considered preliminaries due to the small sample size within this subgroup. Finally, our study design did not include intellectual impairment-only participants without ASD to disentangle the mixture of autistic and intellectual symptoms. CONCLUSIONS: ASD-associated white matter alterations appear driven by individuals with II and potentially further by MV. Results suggest that changes in the corpus callosum and cerebellum are key for psychopathology and cognition associated with ASD. Our work highlights an essential to include understudied subpopulations on the spectrum in research. En ligne : http://dx.doi.org/10.1186/s13229-022-00499-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=477
in Molecular Autism > 13 (2022) . - 21 p.[article] White matter microstructural and morphometric alterations in autism: implications for intellectual capabilities [Texte imprimé et/ou numérique] / Chun-Hung YEH, Auteur ; Rung-Yu TSENG, Auteur ; Hsing-Chang NI, Auteur ; Luca COCCHI, Auteur ; Jung-Chi CHANG, Auteur ; Mei-Yun HSU, Auteur ; En-Nien TU, Auteur ; Yu-Yu WU, Auteur ; Tai-Li CHOU, Auteur ; Susan Shur-Fen GAU, Auteur ; Hsiang-Yuan LIN, Auteur . - 21 p.
Langues : Anglais (eng)
in Molecular Autism > 13 (2022) . - 21 p.
Mots-clés : Adolescent Autism Spectrum Disorder/diagnostic imaging/pathology Autistic Disorder/diagnostic imaging/pathology Brain/diagnostic imaging/pathology Corpus Callosum/diagnostic imaging Diffusion Magnetic Resonance Imaging/methods Humans White Matter/diagnostic imaging/pathology Autism spectrum disorder Cerebellum Diffusion MRI Fixel-based analysis Intellectual disabilities Minimally verbal status Index. décimale : PER Périodiques Résumé : BACKGROUND: Neuroimage literature of autism spectrum disorder (ASD) has a moderate-to-high risk of bias, partially because those combined with intellectual impairment (II) and/or minimally verbal (MV) status are generally ignored. We aimed to provide more comprehensive insights into white matter alterations of ASD, inclusive of individuals with II (ASD-II-Only) or MV expression (ASD-MV). METHODS: Sixty-five participants with ASD (ASD-Whole; 16.6?+?5.9 years; comprising 34 intellectually able youth, ASD-IA, and 31 intellectually impaired youth, ASD-II, including 24 ASD-II-Only plus 7 ASD-MV) and 38 demographic-matched typically developing controls (TDC; 17.3?+?5.6 years) were scanned in accelerated diffusion-weighted MRI. Fixel-based analysis was undertaken to investigate the categorical differences in fiber density (FD), fiber cross section (FC), and a combined index (FDC), and brain symptom/cognition associations. RESULTS: ASD-Whole had reduced FD in the anterior and posterior corpus callosum and left cerebellum Crus I, and smaller FDC in right cerebellum Crus II, compared to TDC. ASD-IA, relative to TDC, had no significant discrepancies, while ASD-II showed almost identical alterations to those from ASD-Whole vs. TDC. ASD-II-Only had greater FD/FDC in the isthmus splenium of callosum than ASD-MV. Autistic severity negatively correlated with FC in right Crus I. Nonverbal full-scale IQ positively correlated with FC/FDC in cerebellum VI. FD/FDC of the right dorsolateral prefrontal cortex showed a diagnosis-by-executive function interaction. LIMITATIONS: We could not preclude the potential effects of age and sex from the ASD cohort, although statistical tests suggested that these factors were not influential. Our results could be confounded by variable psychiatric comorbidities and psychotropic medication uses in our ASD participants recruited from outpatient clinics, which is nevertheless closer to a real-world presentation of ASD. The outcomes related to ASD-MV were considered preliminaries due to the small sample size within this subgroup. Finally, our study design did not include intellectual impairment-only participants without ASD to disentangle the mixture of autistic and intellectual symptoms. CONCLUSIONS: ASD-associated white matter alterations appear driven by individuals with II and potentially further by MV. Results suggest that changes in the corpus callosum and cerebellum are key for psychopathology and cognition associated with ASD. Our work highlights an essential to include understudied subpopulations on the spectrum in research. En ligne : http://dx.doi.org/10.1186/s13229-022-00499-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=477 Autistic adults have poorer quality healthcare and worse health based on self-report data / Elizabeth WEIR in Molecular Autism, 13 (2022)
![]()
[article]
Titre : Autistic adults have poorer quality healthcare and worse health based on self-report data Type de document : Texte imprimé et/ou numérique Auteurs : Elizabeth WEIR, Auteur ; Carrie ALLISON, Auteur ; Simon BARON-COHEN, Auteur Article en page(s) : 23 p. Langues : Anglais (eng) Mots-clés : Adult Autistic Disorder/diagnosis/epidemiology Cross-Sectional Studies Delivery of Health Care Female Health Status Disparities Humans Infant, Newborn Self Report Index. décimale : PER Périodiques Résumé : BACKGROUND: Recent research suggests that autistic individuals have shorter lifespans and experience worse health (greater health burden) than non-autistic individuals. Small, qualitative studies suggest that autistic adults also experience poor self-reported healthcare quality. METHODS: An anonymized, cross-sectional, self-report questionnaire was administered to n=4158 individuals. The study assessed prevalence of chronic health conditions, healthcare quality, differences in overall health inequality score, and effects of the coronavirus pandemic on healthcare quality. We used Fisher's exact tests, binomial logistic regression, and predictive machine learning tools, as appropriate. RESULTS: The final sample included n=2649 participants (n=1285 autistic) aged 16-96 years. Autistic adults reported lower quality healthcare than non-autistic adults across 50/51 items, including poorer access to healthcare and poorer communication, alongside increased anxiety, sensory sensitivity, system-level problems, shutdowns, and meltdowns. Differences between groups were stark: aggregated health inequality scores predicted autism diagnosis, even after stratifying by sex. Autistic adults were also more likely to have chronic health conditions than non-autistic adults. There were no significant differences in healthcare quality for autistic adults before and during the pandemic, although they received relatively poorer quality healthcare than non-autistic adults across both periods. LIMITATIONS: The study's sampling methods are not likely to capture the perspectives of all autistic individuals, especially those with intellectual disability. Both the autistic and control samples are biased towards UK residents, white individuals, those assigned female at birth, and those who completed an undergraduate degree or higher education. As such, these results may limit their generalizability to other groups. Finally, these results relate to self-reported differences in healthcare quality between autistic and non-autistic adults. The observed group differences may in part reflect differences in perception and communication rather than differences in actual healthcare quality. CONCLUSIONS: Autistic adults are more likely to have chronic health conditions alongside self-reported lower quality healthcare than others. Health inequalities between these groups are widespread and dramatic; unfortunately, they existed before and have persisted after the onset of the coronavirus pandemic. En ligne : http://dx.doi.org/10.1186/s13229-022-00501-w Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=491
in Molecular Autism > 13 (2022) . - 23 p.[article] Autistic adults have poorer quality healthcare and worse health based on self-report data [Texte imprimé et/ou numérique] / Elizabeth WEIR, Auteur ; Carrie ALLISON, Auteur ; Simon BARON-COHEN, Auteur . - 23 p.
Langues : Anglais (eng)
in Molecular Autism > 13 (2022) . - 23 p.
Mots-clés : Adult Autistic Disorder/diagnosis/epidemiology Cross-Sectional Studies Delivery of Health Care Female Health Status Disparities Humans Infant, Newborn Self Report Index. décimale : PER Périodiques Résumé : BACKGROUND: Recent research suggests that autistic individuals have shorter lifespans and experience worse health (greater health burden) than non-autistic individuals. Small, qualitative studies suggest that autistic adults also experience poor self-reported healthcare quality. METHODS: An anonymized, cross-sectional, self-report questionnaire was administered to n=4158 individuals. The study assessed prevalence of chronic health conditions, healthcare quality, differences in overall health inequality score, and effects of the coronavirus pandemic on healthcare quality. We used Fisher's exact tests, binomial logistic regression, and predictive machine learning tools, as appropriate. RESULTS: The final sample included n=2649 participants (n=1285 autistic) aged 16-96 years. Autistic adults reported lower quality healthcare than non-autistic adults across 50/51 items, including poorer access to healthcare and poorer communication, alongside increased anxiety, sensory sensitivity, system-level problems, shutdowns, and meltdowns. Differences between groups were stark: aggregated health inequality scores predicted autism diagnosis, even after stratifying by sex. Autistic adults were also more likely to have chronic health conditions than non-autistic adults. There were no significant differences in healthcare quality for autistic adults before and during the pandemic, although they received relatively poorer quality healthcare than non-autistic adults across both periods. LIMITATIONS: The study's sampling methods are not likely to capture the perspectives of all autistic individuals, especially those with intellectual disability. Both the autistic and control samples are biased towards UK residents, white individuals, those assigned female at birth, and those who completed an undergraduate degree or higher education. As such, these results may limit their generalizability to other groups. Finally, these results relate to self-reported differences in healthcare quality between autistic and non-autistic adults. The observed group differences may in part reflect differences in perception and communication rather than differences in actual healthcare quality. CONCLUSIONS: Autistic adults are more likely to have chronic health conditions alongside self-reported lower quality healthcare than others. Health inequalities between these groups are widespread and dramatic; unfortunately, they existed before and have persisted after the onset of the coronavirus pandemic. En ligne : http://dx.doi.org/10.1186/s13229-022-00501-w Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=491 Autism-associated protein POGZ controls ESCs and ESC neural induction by association with esBAF / Xiaoyun SUN in Molecular Autism, 13 (2022)
![]()
[article]
Titre : Autism-associated protein POGZ controls ESCs and ESC neural induction by association with esBAF Type de document : Texte imprimé et/ou numérique Auteurs : Xiaoyun SUN, Auteur ; Linxi CHENG, Auteur ; Yuhua SUN, Auteur Article en page(s) : 24 p. Langues : Anglais (eng) Mots-clés : Animals Autism Spectrum Disorder/genetics Autistic Disorder Cell Differentiation Embryonic Development Embryonic Stem Cells/metabolism Transcription Factors/genetics/metabolism Index. décimale : PER Périodiques Résumé : BACKGROUND: The POGZ gene has been found frequently mutated in neurodevelopmental disorders (NDDs), particularly autism spectrum disorder (ASD) and intellectual disability (ID). However, little is known about its roles in embryonic stem cells (ESCs), neural development and diseases. METHODS: We generated Pogz-/- ESCs and directed ESC differentiation toward a neural fate. We performed biochemistry, ChIP-seq, ATAC-seq, and bioinformatics analyses to understand the role of POGZ. RESULTS: We show that POGZ is required for the maintenance of ESC identity and the up-regulation of neural genes during ESC differentiation toward a neural fate. Genome-wide binding analysis shows that POGZ is primarily localized to gene promoter and enhancer regions. POGZ functions as both a transcriptional activator and repressor, and its loss leads to deregulation of differentiation genes, including neural genes. POGZ physically associates with the SWI-SNF (esBAF) chromatin remodeler complex, and together they modulate enhancer activities via epigenetic modifications such as chromatin remodeling and histone modification. During ESC neural induction, POGZ-mediated recruitment of esBAF/BRG1 and H3K27ac are important for proper expression of neural progenitor genes. LIMITATIONS: The genotype and allele relevant to human neurodevelopmental disorders is heterozygous loss of function. This work is designed to study the effects of loss of POGZ function on ESCs and during ESC neural induction. Also, this work lacks of in vivo validation using animal models. CONCLUSIONS: The data suggest that POGZ is both a transcription factor and a genome regulator, and its loss leads to defects in neural induction and neurogenesis. En ligne : http://dx.doi.org/10.1186/s13229-022-00502-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=491
in Molecular Autism > 13 (2022) . - 24 p.[article] Autism-associated protein POGZ controls ESCs and ESC neural induction by association with esBAF [Texte imprimé et/ou numérique] / Xiaoyun SUN, Auteur ; Linxi CHENG, Auteur ; Yuhua SUN, Auteur . - 24 p.
Langues : Anglais (eng)
in Molecular Autism > 13 (2022) . - 24 p.
Mots-clés : Animals Autism Spectrum Disorder/genetics Autistic Disorder Cell Differentiation Embryonic Development Embryonic Stem Cells/metabolism Transcription Factors/genetics/metabolism Index. décimale : PER Périodiques Résumé : BACKGROUND: The POGZ gene has been found frequently mutated in neurodevelopmental disorders (NDDs), particularly autism spectrum disorder (ASD) and intellectual disability (ID). However, little is known about its roles in embryonic stem cells (ESCs), neural development and diseases. METHODS: We generated Pogz-/- ESCs and directed ESC differentiation toward a neural fate. We performed biochemistry, ChIP-seq, ATAC-seq, and bioinformatics analyses to understand the role of POGZ. RESULTS: We show that POGZ is required for the maintenance of ESC identity and the up-regulation of neural genes during ESC differentiation toward a neural fate. Genome-wide binding analysis shows that POGZ is primarily localized to gene promoter and enhancer regions. POGZ functions as both a transcriptional activator and repressor, and its loss leads to deregulation of differentiation genes, including neural genes. POGZ physically associates with the SWI-SNF (esBAF) chromatin remodeler complex, and together they modulate enhancer activities via epigenetic modifications such as chromatin remodeling and histone modification. During ESC neural induction, POGZ-mediated recruitment of esBAF/BRG1 and H3K27ac are important for proper expression of neural progenitor genes. LIMITATIONS: The genotype and allele relevant to human neurodevelopmental disorders is heterozygous loss of function. This work is designed to study the effects of loss of POGZ function on ESCs and during ESC neural induction. Also, this work lacks of in vivo validation using animal models. CONCLUSIONS: The data suggest that POGZ is both a transcription factor and a genome regulator, and its loss leads to defects in neural induction and neurogenesis. En ligne : http://dx.doi.org/10.1186/s13229-022-00502-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=491 Large multicenter randomized trials in autism: key insights gained from the balovaptan clinical development program / Suma JACOB in Molecular Autism, 13 (2022)
![]()
Maternal age, autistic-like traits and mentalizing as predictors of child autistic-like traits in a population-based cohort / Novika Purnama SARI in Molecular Autism, 13 (2022)
![]()
[article]
Titre : Maternal age, autistic-like traits and mentalizing as predictors of child autistic-like traits in a population-based cohort Type de document : Texte imprimé et/ou numérique Auteurs : Novika Purnama SARI, Auteur ; Pauline W. JANSEN, Auteur ; Laura M. E. BLANKEN, Auteur ; Amber N. V. RUIGROK, Auteur ; Peter PRINZIE, Auteur ; Henning TIEMEIER, Auteur ; Simon BARON-COHEN, Auteur ; Marinus H. VAN IJZENDOORN, Auteur ; Tonya WHITE, Auteur Article en page(s) : 26 p. Langues : Anglais (eng) Mots-clés : Autistic Disorder/epidemiology Child Female Humans Male Maternal Age Mentalization Mothers Netherlands/epidemiology Pregnancy Autistic-like traits Children Mentalizing Index. décimale : PER Périodiques Résumé : BACKGROUND: Many empirical studies suggest that higher maternal age increases the likelihood of having an autistic child. However, little is known about factors that may explain this relationship or if higher maternal age is related to the number of autistic-like traits in offspring. One possibility is that mothers who have a higher number of autistic-like traits, including greater challenges performing mentalizing skills, are delayed in finding a partner. The goal of our study is to assess the relationship between maternal age, mentalizing skills and autistic-like traits as independent predictors of the number of autistic-like traits in offspring. METHODS: In a population-based study in the Netherlands, information on maternal age was collected during pre- and perinatal enrolment. Maternal mentalizing skills and autistic-like traits were assessed using the Reading the Mind in the Eyes Test and the Autism Spectrum Quotient, respectively. Autistic-like traits in children were assessed with the Social Responsiveness Scale. A total of 5718 mother/child dyads had complete data (M(agechild)=13.5 years; 50.2% girls). RESULTS: The relationship between maternal age and autistic-like traits in offspring best fits a U-shaped curve. Furthermore, higher levels of autistic features in mothers are linked to higher levels of autistic-like traits in their children. Lower mentalizing performance in mothers is linked to higher levels of autistic-like traits in their children. LIMITATIONS: We were able to collect data on both autistic-like traits and the mentalizing skills test in a large population of mothers, but we did not collect these data in a large number of the fathers. CONCLUSIONS: The relationships between older and younger mothers may have comparable underlying mechanisms, but it is also possible that the tails of the U-shaped curve are influenced by disparate mechanisms. En ligne : http://dx.doi.org/10.1186/s13229-022-00507-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=491
in Molecular Autism > 13 (2022) . - 26 p.[article] Maternal age, autistic-like traits and mentalizing as predictors of child autistic-like traits in a population-based cohort [Texte imprimé et/ou numérique] / Novika Purnama SARI, Auteur ; Pauline W. JANSEN, Auteur ; Laura M. E. BLANKEN, Auteur ; Amber N. V. RUIGROK, Auteur ; Peter PRINZIE, Auteur ; Henning TIEMEIER, Auteur ; Simon BARON-COHEN, Auteur ; Marinus H. VAN IJZENDOORN, Auteur ; Tonya WHITE, Auteur . - 26 p.
Langues : Anglais (eng)
in Molecular Autism > 13 (2022) . - 26 p.
Mots-clés : Autistic Disorder/epidemiology Child Female Humans Male Maternal Age Mentalization Mothers Netherlands/epidemiology Pregnancy Autistic-like traits Children Mentalizing Index. décimale : PER Périodiques Résumé : BACKGROUND: Many empirical studies suggest that higher maternal age increases the likelihood of having an autistic child. However, little is known about factors that may explain this relationship or if higher maternal age is related to the number of autistic-like traits in offspring. One possibility is that mothers who have a higher number of autistic-like traits, including greater challenges performing mentalizing skills, are delayed in finding a partner. The goal of our study is to assess the relationship between maternal age, mentalizing skills and autistic-like traits as independent predictors of the number of autistic-like traits in offspring. METHODS: In a population-based study in the Netherlands, information on maternal age was collected during pre- and perinatal enrolment. Maternal mentalizing skills and autistic-like traits were assessed using the Reading the Mind in the Eyes Test and the Autism Spectrum Quotient, respectively. Autistic-like traits in children were assessed with the Social Responsiveness Scale. A total of 5718 mother/child dyads had complete data (M(agechild)=13.5 years; 50.2% girls). RESULTS: The relationship between maternal age and autistic-like traits in offspring best fits a U-shaped curve. Furthermore, higher levels of autistic features in mothers are linked to higher levels of autistic-like traits in their children. Lower mentalizing performance in mothers is linked to higher levels of autistic-like traits in their children. LIMITATIONS: We were able to collect data on both autistic-like traits and the mentalizing skills test in a large population of mothers, but we did not collect these data in a large number of the fathers. CONCLUSIONS: The relationships between older and younger mothers may have comparable underlying mechanisms, but it is also possible that the tails of the U-shaped curve are influenced by disparate mechanisms. En ligne : http://dx.doi.org/10.1186/s13229-022-00507-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=491 WDFY3 mutation alters laminar position and morphology of cortical neurons / Zachary A. SCHAAF in Molecular Autism, 13 (2022)
![]()
[article]
Titre : WDFY3 mutation alters laminar position and morphology of cortical neurons Type de document : Texte imprimé et/ou numérique Auteurs : Zachary A. SCHAAF, Auteur ; Lyvin TAT, Auteur ; Noemi CANNIZZARO, Auteur ; Ralph GREEN, Auteur ; Thomas RULICKE, Auteur ; Simon HIPPENMEYER, Auteur ; Konstantinos S. ZARBALIS, Auteur Article en page(s) : 27 p. Langues : Anglais (eng) Mots-clés : Adaptor Proteins, Signal Transducing/genetics Animals Autistic Disorder/genetics Autophagy-Related Proteins/genetics Cerebral Cortex/cytology Humans Mice Mutation Neurogenesis/genetics Neurons/cytology Cerebral cortex Dendrites Dendritic spines Excitatory neurons Neuronal migration Wdfy3 Index. décimale : PER Périodiques Résumé : BACKGROUND: Proper cerebral cortical development depends on the tightly orchestrated migration of newly born neurons from the inner ventricular and subventricular zones to the outer cortical plate. Any disturbance in this process during prenatal stages may lead to neuronal migration disorders (NMDs), which can vary in extent from focal to global. Furthermore, NMDs show a substantial comorbidity with other neurodevelopmental disorders, notably autism spectrum disorders (ASDs). Our previous work demonstrated focal neuronal migration defects in mice carrying loss-of-function alleles of the recognized autism risk gene WDFY3. However, the cellular origins of these defects in Wdfy3 mutant mice remain elusive and uncovering it will provide critical insight into WDFY3-dependent disease pathology. METHODS: Here, in an effort to untangle the origins of NMDs in Wdfy3(lacZ) mice, we employed mosaic analysis with double markers (MADM). MADM technology enabled us to genetically distinctly track and phenotypically analyze mutant and wild-type cells concomitantly in vivo using immunofluorescent techniques. RESULTS: We revealed a cell autonomous requirement of WDFY3 for accurate laminar positioning of cortical projection neurons and elimination of mispositioned cells during early postnatal life. In addition, we identified significant deviations in dendritic arborization, as well as synaptic density and morphology between wild type, heterozygous, and homozygous Wdfy3 mutant neurons in Wdfy3-MADM reporter mice at postnatal stages. LIMITATIONS: While Wdfy3 mutant mice have provided valuable insight into prenatal aspects of ASD pathology that remain inaccessible to investigation in humans, like most animal models, they do not a perfectly replicate all aspects of human ASD biology. The lack of human data makes it indeterminate whether morphological deviations described here apply to ASD patients or some of the other neurodevelopmental conditions associated with WDFY3 mutation. CONCLUSIONS: Our genetic approach revealed several cell autonomous requirements of WDFY3 in neuronal development that could underlie the pathogenic mechanisms of WDFY3-related neurodevelopmental conditions. The results are also consistent with findings in other ASD animal models and patients and suggest an important role for WDFY3 in regulating neuronal function and interconnectivity in postnatal life. En ligne : http://dx.doi.org/10.1186/s13229-022-00508-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=491
in Molecular Autism > 13 (2022) . - 27 p.[article] WDFY3 mutation alters laminar position and morphology of cortical neurons [Texte imprimé et/ou numérique] / Zachary A. SCHAAF, Auteur ; Lyvin TAT, Auteur ; Noemi CANNIZZARO, Auteur ; Ralph GREEN, Auteur ; Thomas RULICKE, Auteur ; Simon HIPPENMEYER, Auteur ; Konstantinos S. ZARBALIS, Auteur . - 27 p.
Langues : Anglais (eng)
in Molecular Autism > 13 (2022) . - 27 p.
Mots-clés : Adaptor Proteins, Signal Transducing/genetics Animals Autistic Disorder/genetics Autophagy-Related Proteins/genetics Cerebral Cortex/cytology Humans Mice Mutation Neurogenesis/genetics Neurons/cytology Cerebral cortex Dendrites Dendritic spines Excitatory neurons Neuronal migration Wdfy3 Index. décimale : PER Périodiques Résumé : BACKGROUND: Proper cerebral cortical development depends on the tightly orchestrated migration of newly born neurons from the inner ventricular and subventricular zones to the outer cortical plate. Any disturbance in this process during prenatal stages may lead to neuronal migration disorders (NMDs), which can vary in extent from focal to global. Furthermore, NMDs show a substantial comorbidity with other neurodevelopmental disorders, notably autism spectrum disorders (ASDs). Our previous work demonstrated focal neuronal migration defects in mice carrying loss-of-function alleles of the recognized autism risk gene WDFY3. However, the cellular origins of these defects in Wdfy3 mutant mice remain elusive and uncovering it will provide critical insight into WDFY3-dependent disease pathology. METHODS: Here, in an effort to untangle the origins of NMDs in Wdfy3(lacZ) mice, we employed mosaic analysis with double markers (MADM). MADM technology enabled us to genetically distinctly track and phenotypically analyze mutant and wild-type cells concomitantly in vivo using immunofluorescent techniques. RESULTS: We revealed a cell autonomous requirement of WDFY3 for accurate laminar positioning of cortical projection neurons and elimination of mispositioned cells during early postnatal life. In addition, we identified significant deviations in dendritic arborization, as well as synaptic density and morphology between wild type, heterozygous, and homozygous Wdfy3 mutant neurons in Wdfy3-MADM reporter mice at postnatal stages. LIMITATIONS: While Wdfy3 mutant mice have provided valuable insight into prenatal aspects of ASD pathology that remain inaccessible to investigation in humans, like most animal models, they do not a perfectly replicate all aspects of human ASD biology. The lack of human data makes it indeterminate whether morphological deviations described here apply to ASD patients or some of the other neurodevelopmental conditions associated with WDFY3 mutation. CONCLUSIONS: Our genetic approach revealed several cell autonomous requirements of WDFY3 in neuronal development that could underlie the pathogenic mechanisms of WDFY3-related neurodevelopmental conditions. The results are also consistent with findings in other ASD animal models and patients and suggest an important role for WDFY3 in regulating neuronal function and interconnectivity in postnatal life. En ligne : http://dx.doi.org/10.1186/s13229-022-00508-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=491 Infants later diagnosed with autism have lower canonical babbling ratios in the first year of life / L. D. YANKOWITZ in Molecular Autism, 13 (2022)
![]()
[article]
Titre : Infants later diagnosed with autism have lower canonical babbling ratios in the first year of life Type de document : Texte imprimé et/ou numérique Auteurs : L. D. YANKOWITZ, Auteur ; V. PETRULLA, Auteur ; S. PLATE, Auteur ; B. TUNC, Auteur ; W. GUTHRIE, Auteur ; S. S. MEERA, Auteur ; K. TENA, Auteur ; J. PANDEY, Auteur ; M. R. SWANSON, Auteur ; J. R. Jr PRUETT, Auteur ; M. COLA, Auteur ; A. RUSSELL, Auteur ; N. MARRUS, Auteur ; Heather C. HAZLETT, Auteur ; K. BOTTERON, Auteur ; J. N. CONSTANTINO, Auteur ; Stephen R. DAGER, Auteur ; A. ESTES, Auteur ; Lonnie ZWAIGENBAUM, Auteur ; J. PIVEN, Auteur ; Robert T. SCHULTZ, Auteur ; Julia PARISH-MORRIS, Auteur Article en page(s) : 28 p. Langues : Anglais (eng) Mots-clés : Autism Spectrum Disorder/diagnosis Autistic Disorder Humans Infant Language Development Disorders/diagnosis Longitudinal Studies Reproducibility of Results Index. décimale : PER Périodiques Résumé : BACKGROUND: Canonical babbling-producing syllables with a mature consonant, full vowel, and smooth transition-is an important developmental milestone that typically occurs in the first year of life. Some studies indicate delayed or reduced canonical babbling in infants at high familial likelihood for autism spectrum disorder (ASD) or who later receive an ASD diagnosis, but evidence is mixed. More refined characterization of babbling in the first year of life in infants with high likelihood for ASD is needed. METHODS: Vocalizations produced at 6 and 12 months by infants (n=267) taking part in a longitudinal study were coded for canonical and non-canonical syllables. Infants were categorized as low familial likelihood (LL), high familial likelihood diagnosed with ASD at 24 months (HL-ASD) or not diagnosed (HL-Neg). Language delay was assessed based on 24-month expressive and receptive language scores. Canonical babble ratio (CBR) was calculated by dividing the number of canonical syllables by the number of total syllables. Generalized linear (mixed) models were used to assess the relationship between group membership and CBR, controlling for site, sex, and maternal education. Logistic regression was used to assess whether canonical babbling ratios at 6 and 12 months predict 24-month diagnostic outcome. RESULTS: No diagnostic group differences in CBR were detected at 6 months, but HL-ASD infants produced significantly lower CBR than both the HL-Neg and LL groups at 12 months. HL-Neg infants with language delay also showed reduced CBR at 12 months. Neither 6- nor 12-month CBR was significant predictors of 24-month diagnostic outcome (ASD versus no ASD) in logistic regression. LIMITATIONS: Small numbers of vocalizations produced by infants at 6 months may limit the reliability of CBR estimates. It is not known if results generalize to infants who are not at high familial likelihood, or infants from more diverse racial and socioeconomic backgrounds. CONCLUSIONS: Lower canonical babbling ratios are apparent by the end of the first year of life in ASD regardless of later language delay, but are also observed for infants with later language delay without ASD. Canonical babbling may lack specificity as an early marker when used on its own. En ligne : http://dx.doi.org/10.1186/s13229-022-00503-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=491
in Molecular Autism > 13 (2022) . - 28 p.[article] Infants later diagnosed with autism have lower canonical babbling ratios in the first year of life [Texte imprimé et/ou numérique] / L. D. YANKOWITZ, Auteur ; V. PETRULLA, Auteur ; S. PLATE, Auteur ; B. TUNC, Auteur ; W. GUTHRIE, Auteur ; S. S. MEERA, Auteur ; K. TENA, Auteur ; J. PANDEY, Auteur ; M. R. SWANSON, Auteur ; J. R. Jr PRUETT, Auteur ; M. COLA, Auteur ; A. RUSSELL, Auteur ; N. MARRUS, Auteur ; Heather C. HAZLETT, Auteur ; K. BOTTERON, Auteur ; J. N. CONSTANTINO, Auteur ; Stephen R. DAGER, Auteur ; A. ESTES, Auteur ; Lonnie ZWAIGENBAUM, Auteur ; J. PIVEN, Auteur ; Robert T. SCHULTZ, Auteur ; Julia PARISH-MORRIS, Auteur . - 28 p.
Langues : Anglais (eng)
in Molecular Autism > 13 (2022) . - 28 p.
Mots-clés : Autism Spectrum Disorder/diagnosis Autistic Disorder Humans Infant Language Development Disorders/diagnosis Longitudinal Studies Reproducibility of Results Index. décimale : PER Périodiques Résumé : BACKGROUND: Canonical babbling-producing syllables with a mature consonant, full vowel, and smooth transition-is an important developmental milestone that typically occurs in the first year of life. Some studies indicate delayed or reduced canonical babbling in infants at high familial likelihood for autism spectrum disorder (ASD) or who later receive an ASD diagnosis, but evidence is mixed. More refined characterization of babbling in the first year of life in infants with high likelihood for ASD is needed. METHODS: Vocalizations produced at 6 and 12 months by infants (n=267) taking part in a longitudinal study were coded for canonical and non-canonical syllables. Infants were categorized as low familial likelihood (LL), high familial likelihood diagnosed with ASD at 24 months (HL-ASD) or not diagnosed (HL-Neg). Language delay was assessed based on 24-month expressive and receptive language scores. Canonical babble ratio (CBR) was calculated by dividing the number of canonical syllables by the number of total syllables. Generalized linear (mixed) models were used to assess the relationship between group membership and CBR, controlling for site, sex, and maternal education. Logistic regression was used to assess whether canonical babbling ratios at 6 and 12 months predict 24-month diagnostic outcome. RESULTS: No diagnostic group differences in CBR were detected at 6 months, but HL-ASD infants produced significantly lower CBR than both the HL-Neg and LL groups at 12 months. HL-Neg infants with language delay also showed reduced CBR at 12 months. Neither 6- nor 12-month CBR was significant predictors of 24-month diagnostic outcome (ASD versus no ASD) in logistic regression. LIMITATIONS: Small numbers of vocalizations produced by infants at 6 months may limit the reliability of CBR estimates. It is not known if results generalize to infants who are not at high familial likelihood, or infants from more diverse racial and socioeconomic backgrounds. CONCLUSIONS: Lower canonical babbling ratios are apparent by the end of the first year of life in ASD regardless of later language delay, but are also observed for infants with later language delay without ASD. Canonical babbling may lack specificity as an early marker when used on its own. En ligne : http://dx.doi.org/10.1186/s13229-022-00503-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=491 Deletion of Fmr1 in parvalbumin-expressing neurons results in dysregulated translation and selective behavioral deficits associated with fragile X syndrome / Magdalena KALINOWSKA in Molecular Autism, 13 (2022)
![]()
[article]
Titre : Deletion of Fmr1 in parvalbumin-expressing neurons results in dysregulated translation and selective behavioral deficits associated with fragile X syndrome Type de document : Texte imprimé et/ou numérique Auteurs : Magdalena KALINOWSKA, Auteur ; Mathijs B. VAN DER LEI, Auteur ; Michael KITIASHVILI, Auteur ; Maggie MAMCARZ, Auteur ; Mauricio M. OLIVEIRA, Auteur ; Francesco LONGO, Auteur ; Eric KLANN, Auteur Article en page(s) : 29 p. Langues : Anglais (eng) Mots-clés : Animals Autism Spectrum Disorder/metabolism Disease Models, Animal Fragile X Mental Retardation Protein/genetics/metabolism Fragile X Syndrome/genetics/metabolism/pathology Mice Mice, Knockout Neurons/metabolism/pathology Parvalbumins/metabolism RNA, Messenger/metabolism Somatostatin/metabolism Autism Behavior Fmrp Fragile X syndrome Inhibitory neurons Protein synthesis Index. décimale : PER Périodiques Résumé : BACKGROUND: Fragile X syndrome (FXS), the most common genetic cause of autism spectrum disorder and intellectual disability, is caused by the lack of fragile X mental retardation protein (FMRP) expression. FMRP is an mRNA binding protein with functions in mRNA transport, localization, and translational control. In Fmr1 knockout mice, dysregulated translation has been linked to pathophysiology, including abnormal synaptic function and dendritic morphology, and autistic-like behavioral phenotypes. The role of FMRP in morphology and function of excitatory neurons has been well studied in mice lacking Fmr1, but the impact of Fmr1 deletion on inhibitory neurons remains less characterized. Moreover, the contribution of FMRP in different cell types to FXS pathophysiology is not well defined. We sought to characterize whether FMRP loss in parvalbumin or somatostatin-expressing neurons results in FXS-like deficits in mice. METHODS: We used Cre-lox recombinase technology to generate two lines of conditional knockout mice lacking FMRP in either parvalbumin or somatostatin-expressing cells and carried out a battery of behavioral tests to assess motor function, anxiety, repetitive, stereotypic, social behaviors, and learning and memory. In addition, we used fluorescent non-canonical amino acid tagging along with immunostaining to determine whether de novo protein synthesis is dysregulated in parvalbumin or somatostatin-expressing neurons. RESULTS: De novo protein synthesis was elevated in hippocampal parvalbumin and somatostatin-expressing inhibitory neurons in Fmr1 knockout mice. Cell type-specific deletion of Fmr1 in parvalbumin-expressing neurons resulted in anxiety-like behavior, impaired social behavior, and dysregulated de novo protein synthesis. In contrast, deletion of Fmr1 in somatostatin-expressing neurons did not result in behavioral abnormalities and did not significantly impact de novo protein synthesis. This is the first report of how loss of FMRP in two specific subtypes of inhibitory neurons is associated with distinct FXS-like abnormalities. LIMITATIONS: The mouse models we generated are limited by whole body knockout of FMRP in parvalbumin or somatostatin-expressing cells and further studies are needed to establish a causal relationship between cellular deficits and FXS-like behaviors. CONCLUSIONS: Our findings indicate a cell type-specific role for FMRP in parvalbumin-expressing neurons in regulating distinct behavioral features associated with FXS. En ligne : http://dx.doi.org/10.1186/s13229-022-00509-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=491
in Molecular Autism > 13 (2022) . - 29 p.[article] Deletion of Fmr1 in parvalbumin-expressing neurons results in dysregulated translation and selective behavioral deficits associated with fragile X syndrome [Texte imprimé et/ou numérique] / Magdalena KALINOWSKA, Auteur ; Mathijs B. VAN DER LEI, Auteur ; Michael KITIASHVILI, Auteur ; Maggie MAMCARZ, Auteur ; Mauricio M. OLIVEIRA, Auteur ; Francesco LONGO, Auteur ; Eric KLANN, Auteur . - 29 p.
Langues : Anglais (eng)
in Molecular Autism > 13 (2022) . - 29 p.
Mots-clés : Animals Autism Spectrum Disorder/metabolism Disease Models, Animal Fragile X Mental Retardation Protein/genetics/metabolism Fragile X Syndrome/genetics/metabolism/pathology Mice Mice, Knockout Neurons/metabolism/pathology Parvalbumins/metabolism RNA, Messenger/metabolism Somatostatin/metabolism Autism Behavior Fmrp Fragile X syndrome Inhibitory neurons Protein synthesis Index. décimale : PER Périodiques Résumé : BACKGROUND: Fragile X syndrome (FXS), the most common genetic cause of autism spectrum disorder and intellectual disability, is caused by the lack of fragile X mental retardation protein (FMRP) expression. FMRP is an mRNA binding protein with functions in mRNA transport, localization, and translational control. In Fmr1 knockout mice, dysregulated translation has been linked to pathophysiology, including abnormal synaptic function and dendritic morphology, and autistic-like behavioral phenotypes. The role of FMRP in morphology and function of excitatory neurons has been well studied in mice lacking Fmr1, but the impact of Fmr1 deletion on inhibitory neurons remains less characterized. Moreover, the contribution of FMRP in different cell types to FXS pathophysiology is not well defined. We sought to characterize whether FMRP loss in parvalbumin or somatostatin-expressing neurons results in FXS-like deficits in mice. METHODS: We used Cre-lox recombinase technology to generate two lines of conditional knockout mice lacking FMRP in either parvalbumin or somatostatin-expressing cells and carried out a battery of behavioral tests to assess motor function, anxiety, repetitive, stereotypic, social behaviors, and learning and memory. In addition, we used fluorescent non-canonical amino acid tagging along with immunostaining to determine whether de novo protein synthesis is dysregulated in parvalbumin or somatostatin-expressing neurons. RESULTS: De novo protein synthesis was elevated in hippocampal parvalbumin and somatostatin-expressing inhibitory neurons in Fmr1 knockout mice. Cell type-specific deletion of Fmr1 in parvalbumin-expressing neurons resulted in anxiety-like behavior, impaired social behavior, and dysregulated de novo protein synthesis. In contrast, deletion of Fmr1 in somatostatin-expressing neurons did not result in behavioral abnormalities and did not significantly impact de novo protein synthesis. This is the first report of how loss of FMRP in two specific subtypes of inhibitory neurons is associated with distinct FXS-like abnormalities. LIMITATIONS: The mouse models we generated are limited by whole body knockout of FMRP in parvalbumin or somatostatin-expressing cells and further studies are needed to establish a causal relationship between cellular deficits and FXS-like behaviors. CONCLUSIONS: Our findings indicate a cell type-specific role for FMRP in parvalbumin-expressing neurons in regulating distinct behavioral features associated with FXS. En ligne : http://dx.doi.org/10.1186/s13229-022-00509-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=491 Diagnostic validity of Autism Diagnostic Observation Schedule, second edition (K-ADOS-2) in the Korean population / So Yoon KIM in Molecular Autism, 13 (2022)
![]()
[article]
Titre : Diagnostic validity of Autism Diagnostic Observation Schedule, second edition (K-ADOS-2) in the Korean population Type de document : Texte imprimé et/ou numérique Auteurs : So Yoon KIM, Auteur ; Miae OH, Auteur ; Guiyoung BONG, Auteur ; Da-Yea SONG, Auteur ; Nan-He YOON, Auteur ; Joo Hyun KIM, Auteur ; Hee Jeong YOO, Auteur Article en page(s) : 30 p. Langues : Anglais (eng) Mots-clés : Adolescent Adult Asian People Autism Spectrum Disorder/diagnosis Autistic Disorder Child Female Humans Male ROC Curve Reproducibility of Results Ados-2 Autism Diagnosis Validity Index. décimale : PER Périodiques Résumé : BACKGROUND: Although the Korean version of the Autism Diagnostic Observation Schedule-2 (K-ADOS-2) is widely being used to diagnose autism spectrum disorder (ASD) in South Korea, no previous study has examined the validity and reliability of all modules of K-ADOS-2 across a wide age range, particularly older children, adolescents, and adults. METHOD: Data from 2,158 participants were included (mean age=79.7 months; 73.6% male): 1473 participants with ASD and 685 participants without ASD (Toddler Module, n=289; Module 1, n=642; Module 2 n=574; Module 3 n=411; Module 4, n=242). Participants completed a battery of tests, including the K-ADOS or K-ADOS-2 and other existing diagnostic instruments. Sensitivity, specificity, area under the receiver operating characteristic (ROC) curve, positive predictive value (PPV), negative predictive value (NPV), Cohen's kappa (k), and agreement with existing diagnostic instruments were computed. Cronbach's Î+ values were also calculated. RESULTS: All developmental cells of the K-ADOS-2 showed sufficient ranges of sensitivity 85.4-100.0%; specificity, 80.4-96.8%; area under the ROC curve, .90-.97; PPV, 77.8-99.3%; NPV, 80.6-100.0%; and k values, .83-.92. The kappa agreements of developmental cells with existing diagnostic instruments ranged from .20 to .90. Cronbach's Î+ values ranged from .82 to .91 across all developmental cells. LIMITATION: The best-estimate clinical diagnoses made in this study were not independent of the K-ADOS-2 scores. Some modules did not include balanced numbers of participants in terms of gender and diagnostic status. CONCLUSION: The K-ADOS-2 is a valid and reliable instrument in diagnosing ASD in South Korea. Future studies exploring the effectiveness of the K-ADOS-2 in capturing restricted, repetitive behaviors and differentiating ASD from other developmental disabilities are needed. En ligne : http://dx.doi.org/10.1186/s13229-022-00506-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=491
in Molecular Autism > 13 (2022) . - 30 p.[article] Diagnostic validity of Autism Diagnostic Observation Schedule, second edition (K-ADOS-2) in the Korean population [Texte imprimé et/ou numérique] / So Yoon KIM, Auteur ; Miae OH, Auteur ; Guiyoung BONG, Auteur ; Da-Yea SONG, Auteur ; Nan-He YOON, Auteur ; Joo Hyun KIM, Auteur ; Hee Jeong YOO, Auteur . - 30 p.
Langues : Anglais (eng)
in Molecular Autism > 13 (2022) . - 30 p.
Mots-clés : Adolescent Adult Asian People Autism Spectrum Disorder/diagnosis Autistic Disorder Child Female Humans Male ROC Curve Reproducibility of Results Ados-2 Autism Diagnosis Validity Index. décimale : PER Périodiques Résumé : BACKGROUND: Although the Korean version of the Autism Diagnostic Observation Schedule-2 (K-ADOS-2) is widely being used to diagnose autism spectrum disorder (ASD) in South Korea, no previous study has examined the validity and reliability of all modules of K-ADOS-2 across a wide age range, particularly older children, adolescents, and adults. METHOD: Data from 2,158 participants were included (mean age=79.7 months; 73.6% male): 1473 participants with ASD and 685 participants without ASD (Toddler Module, n=289; Module 1, n=642; Module 2 n=574; Module 3 n=411; Module 4, n=242). Participants completed a battery of tests, including the K-ADOS or K-ADOS-2 and other existing diagnostic instruments. Sensitivity, specificity, area under the receiver operating characteristic (ROC) curve, positive predictive value (PPV), negative predictive value (NPV), Cohen's kappa (k), and agreement with existing diagnostic instruments were computed. Cronbach's Î+ values were also calculated. RESULTS: All developmental cells of the K-ADOS-2 showed sufficient ranges of sensitivity 85.4-100.0%; specificity, 80.4-96.8%; area under the ROC curve, .90-.97; PPV, 77.8-99.3%; NPV, 80.6-100.0%; and k values, .83-.92. The kappa agreements of developmental cells with existing diagnostic instruments ranged from .20 to .90. Cronbach's Î+ values ranged from .82 to .91 across all developmental cells. LIMITATION: The best-estimate clinical diagnoses made in this study were not independent of the K-ADOS-2 scores. Some modules did not include balanced numbers of participants in terms of gender and diagnostic status. CONCLUSION: The K-ADOS-2 is a valid and reliable instrument in diagnosing ASD in South Korea. Future studies exploring the effectiveness of the K-ADOS-2 in capturing restricted, repetitive behaviors and differentiating ASD from other developmental disabilities are needed. En ligne : http://dx.doi.org/10.1186/s13229-022-00506-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=491 The longitudinal bidirectional relationship between autistic traits and brain morphology from childhood to adolescence: a population-based cohort study / Melisa DURKUT in Molecular Autism, 13 (2022)
![]()
[article]
Titre : The longitudinal bidirectional relationship between autistic traits and brain morphology from childhood to adolescence: a population-based cohort study Type de document : Texte imprimé et/ou numérique Auteurs : Melisa DURKUT, Auteur ; Elisabet BLOK, Auteur ; Anna SULERI, Auteur ; Tonya WHITE, Auteur Article en page(s) : 31 p. Langues : Anglais (eng) Mots-clés : Adolescent Autistic Disorder/complications/diagnostic imaging Brain/diagnostic imaging Child Cohort Studies Cross-Sectional Studies Humans Longitudinal Studies Autism spectrum disorder Child/adolescent psychiatry Development Neurodevelopmental disorders Neuroimaging Index. décimale : PER Périodiques Résumé : OBJECTIVE: Autistic traits are associated with alterations in brain morphology. However, the anatomic location of these differences and their developmental trajectories are unclear. The primary objective of this longitudinal study was to explore the bidirectional relationship between autistic traits and brain morphology from childhood to adolescence. METHOD: Participants were drawn from a population-based cohort. Cross-sectional and longitudinal analyses included 1950 (mean age 13.5) and 304 participants (mean ages 6.2 and 13.5), respectively. Autistic traits were measured with the Social Responsiveness Scale. Global brain measures and surface-based measures of gyrification, cortical thickness and surface area were obtained from T(1)-weighted MRI scans. Cross-sectional associations were assessed using linear regression analyses. Cross-lagged panel models were used to determine the longitudinal bidirectional relationship between autistic traits and brain morphology. RESULTS: Cross-sectionally, higher levels of autistic traits in adolescents are associated with lower gyrification in the pars opercularis, insula and superior temporal cortex; smaller surface area in the middle temporal and postcentral cortex; larger cortical thickness in the superior frontal cortex; and smaller cerebellum cortex volume. Longitudinally, both autistic traits and brain measures were quite stable, with neither brain measures predicting changes in autistic traits, nor vice-versa. LIMITATIONS: Autistic traits were assessed at only two time points, and thus we could not distinguish within- versus between-person effects. Furthermore, two different MRI scanners were used between baseline and follow-up for imaging data acquisition. CONCLUSIONS: Our findings point to early changes in brain morphology in children with autistic symptoms that remain quite stable over time. The observed relationship did not change substantially after excluding children with high levels of autistic traits, bolstering the evidence for the extension of the neurobiology of autistic traits to the general population. En ligne : http://dx.doi.org/10.1186/s13229-022-00504-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=491
in Molecular Autism > 13 (2022) . - 31 p.[article] The longitudinal bidirectional relationship between autistic traits and brain morphology from childhood to adolescence: a population-based cohort study [Texte imprimé et/ou numérique] / Melisa DURKUT, Auteur ; Elisabet BLOK, Auteur ; Anna SULERI, Auteur ; Tonya WHITE, Auteur . - 31 p.
Langues : Anglais (eng)
in Molecular Autism > 13 (2022) . - 31 p.
Mots-clés : Adolescent Autistic Disorder/complications/diagnostic imaging Brain/diagnostic imaging Child Cohort Studies Cross-Sectional Studies Humans Longitudinal Studies Autism spectrum disorder Child/adolescent psychiatry Development Neurodevelopmental disorders Neuroimaging Index. décimale : PER Périodiques Résumé : OBJECTIVE: Autistic traits are associated with alterations in brain morphology. However, the anatomic location of these differences and their developmental trajectories are unclear. The primary objective of this longitudinal study was to explore the bidirectional relationship between autistic traits and brain morphology from childhood to adolescence. METHOD: Participants were drawn from a population-based cohort. Cross-sectional and longitudinal analyses included 1950 (mean age 13.5) and 304 participants (mean ages 6.2 and 13.5), respectively. Autistic traits were measured with the Social Responsiveness Scale. Global brain measures and surface-based measures of gyrification, cortical thickness and surface area were obtained from T(1)-weighted MRI scans. Cross-sectional associations were assessed using linear regression analyses. Cross-lagged panel models were used to determine the longitudinal bidirectional relationship between autistic traits and brain morphology. RESULTS: Cross-sectionally, higher levels of autistic traits in adolescents are associated with lower gyrification in the pars opercularis, insula and superior temporal cortex; smaller surface area in the middle temporal and postcentral cortex; larger cortical thickness in the superior frontal cortex; and smaller cerebellum cortex volume. Longitudinally, both autistic traits and brain measures were quite stable, with neither brain measures predicting changes in autistic traits, nor vice-versa. LIMITATIONS: Autistic traits were assessed at only two time points, and thus we could not distinguish within- versus between-person effects. Furthermore, two different MRI scanners were used between baseline and follow-up for imaging data acquisition. CONCLUSIONS: Our findings point to early changes in brain morphology in children with autistic symptoms that remain quite stable over time. The observed relationship did not change substantially after excluding children with high levels of autistic traits, bolstering the evidence for the extension of the neurobiology of autistic traits to the general population. En ligne : http://dx.doi.org/10.1186/s13229-022-00504-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=491 Autism traits outweigh alexithymia traits in the explanation of mentalising performance in adults with autism but not in adults with rejected autism diagnosis / Christine M. FALTER-WAGNER in Molecular Autism, 13 (2022)
![]()
[article]
Titre : Autism traits outweigh alexithymia traits in the explanation of mentalising performance in adults with autism but not in adults with rejected autism diagnosis Type de document : Texte imprimé et/ou numérique Auteurs : Christine M. FALTER-WAGNER, Auteur ; Carola BLOCH, Auteur ; Lana BURGHOF, Auteur ; Fritz-Georg LEHNHARDT, Auteur ; Kai VOGELEY, Auteur Article en page(s) : 32 p. Langues : Anglais (eng) Mots-clés : Adult Affective Symptoms/complications Autism Spectrum Disorder/psychology Autistic Disorder/psychology Cross-Sectional Studies Humans Phenotype Alexithymia Autism Dominance analysis Mentalising Index. décimale : PER Périodiques Résumé : BACKGROUND: Pronounced alexithymia traits have been found in autism spectrum disorder (ASD) and recent research has been carving out the impact alexithymia traits might have on mentalising deficits associated with ASD. METHOD: In this cross-sectional study, a large representative referral population for diagnostic examination for possible ASD (n=400) was screened for clinical alexithymia with a German version of the Reading the Mind in the Eyes test (RME). In contrast to previous attempts to carve out the impact of alexithymia traits on mentalising deficits though, we employed dominance analysis to account for the correlation between predictors. The relative relationship between alexithymia traits and autism traits with RME performance was investigated in the group of individuals with confirmed ASD diagnosis (N=281) and compared to the clinical referral sample in which ASD was ruled out (N=119). RESULTS: Dominance analysis revealed autism traits to be the strongest predictor for reduced mentalising skills in the ASD sample, whereas alexithymia contributed significantly less. In the sample of individuals with ruled out diagnosis, autism traits were the strongest predictor, but alexithymia traits were in sum equally associated to mentalising, with the External-Oriented Thinking subscale as an important predictor of this association. LIMITATIONS: It needs to be considered that the cross-sectional study design does not allow for causal inference. Furthermore, mentalising is a highly facetted capacity and measurements need to reduce this complexity into simple quantities which limits the generalizability of results. DISCUSSION: While alexithymia traits should be considered for their mental health importance, they do not dominate the explanation of reduced mentalising skills in individuals with ASD, but they might do to a larger degree in individuals with ruled out ASD. En ligne : http://dx.doi.org/10.1186/s13229-022-00510-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=491
in Molecular Autism > 13 (2022) . - 32 p.[article] Autism traits outweigh alexithymia traits in the explanation of mentalising performance in adults with autism but not in adults with rejected autism diagnosis [Texte imprimé et/ou numérique] / Christine M. FALTER-WAGNER, Auteur ; Carola BLOCH, Auteur ; Lana BURGHOF, Auteur ; Fritz-Georg LEHNHARDT, Auteur ; Kai VOGELEY, Auteur . - 32 p.
Langues : Anglais (eng)
in Molecular Autism > 13 (2022) . - 32 p.
Mots-clés : Adult Affective Symptoms/complications Autism Spectrum Disorder/psychology Autistic Disorder/psychology Cross-Sectional Studies Humans Phenotype Alexithymia Autism Dominance analysis Mentalising Index. décimale : PER Périodiques Résumé : BACKGROUND: Pronounced alexithymia traits have been found in autism spectrum disorder (ASD) and recent research has been carving out the impact alexithymia traits might have on mentalising deficits associated with ASD. METHOD: In this cross-sectional study, a large representative referral population for diagnostic examination for possible ASD (n=400) was screened for clinical alexithymia with a German version of the Reading the Mind in the Eyes test (RME). In contrast to previous attempts to carve out the impact of alexithymia traits on mentalising deficits though, we employed dominance analysis to account for the correlation between predictors. The relative relationship between alexithymia traits and autism traits with RME performance was investigated in the group of individuals with confirmed ASD diagnosis (N=281) and compared to the clinical referral sample in which ASD was ruled out (N=119). RESULTS: Dominance analysis revealed autism traits to be the strongest predictor for reduced mentalising skills in the ASD sample, whereas alexithymia contributed significantly less. In the sample of individuals with ruled out diagnosis, autism traits were the strongest predictor, but alexithymia traits were in sum equally associated to mentalising, with the External-Oriented Thinking subscale as an important predictor of this association. LIMITATIONS: It needs to be considered that the cross-sectional study design does not allow for causal inference. Furthermore, mentalising is a highly facetted capacity and measurements need to reduce this complexity into simple quantities which limits the generalizability of results. DISCUSSION: While alexithymia traits should be considered for their mental health importance, they do not dominate the explanation of reduced mentalising skills in individuals with ASD, but they might do to a larger degree in individuals with ruled out ASD. En ligne : http://dx.doi.org/10.1186/s13229-022-00510-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=491 Imbalance of flight-freeze responses and their cellular correlates in the Nlgn3(-/y) rat model of autism / Natasha J. ANSTEY in Molecular Autism, 13 (2022)
![]()
[article]
Titre : Imbalance of flight-freeze responses and their cellular correlates in the Nlgn3(-/y) rat model of autism Type de document : Texte imprimé et/ou numérique Auteurs : Natasha J. ANSTEY, Auteur ; Vijayakumar KAPGAL, Auteur ; Shashank TIWARI, Auteur ; Thomas C. WATSON, Auteur ; Anna K. H. TOFT, Auteur ; Owen R. DANDO, Auteur ; Felicity H. INKPEN, Auteur ; Paul S. BAXTER, Auteur ; Zrinko KOZIĆ, Auteur ; Adam D. JACKSON, Auteur ; Xin HE, Auteur ; Mohammad SARFARAZ NAWAZ, Auteur ; Aiman KAYENAAT, Auteur ; Aditi BHATTACHARYA, Auteur ; David J. A. WYLLIE, Auteur ; Sumantra CHATTARJI, Auteur ; Emma R. WOOD, Auteur ; Oliver HARDT, Auteur ; Peter C. KIND, Auteur Article en page(s) : 34 p. Langues : Anglais (eng) Mots-clés : Animals Autistic Disorder/metabolism Fear/physiology Freezing Humans Neurons/physiology Periaqueductal Gray/metabolism Rats Autism Fear Flight Intellectual disability Neuroligin-3 Periaqueductal grey Index. décimale : PER Périodiques Résumé : BACKGROUND: Mutations in the postsynaptic transmembrane protein neuroligin-3 are highly correlative with autism spectrum disorders (ASDs) and intellectual disabilities (IDs). Fear learning is well studied in models of these disorders, however differences in fear response behaviours are often overlooked. We aim to examine fear behaviour and its cellular underpinnings in a rat model of ASD/ID lacking Nlgn3. METHODS: This study uses a range of behavioural tests to understand differences in fear response behaviour in Nlgn3(-/y) rats. Following this, we examined the physiological underpinnings of this in neurons of the periaqueductal grey (PAG), a midbrain area involved in flight-or-freeze responses. We used whole-cell patch-clamp recordings from ex vivo PAG slices, in addition to in vivo local-field potential recordings and electrical stimulation of the PAG in wildtype and Nlgn3(-/y) rats. We analysed behavioural data with two- and three-way ANOVAS and electrophysiological data with generalised linear mixed modelling (GLMM). RESULTS: We observed that, unlike the wildtype, Nlgn3(-/y) rats are more likely to response with flight rather than freezing in threatening situations. Electrophysiological findings were in agreement with these behavioural outcomes. We found in ex vivo slices from Nlgn3(-/y) rats that neurons in dorsal PAG (dPAG) showed intrinsic hyperexcitability compared to wildtype. Similarly, stimulating dPAG in vivo revealed that lower magnitudes sufficed to evoke flight behaviour in Nlgn3(-/y) than wildtype rats, indicating the functional impact of the increased cellular excitability. LIMITATIONS: Our findings do not examine what specific cell type in the PAG is likely responsible for these phenotypes. Furthermore, we have focussed on phenotypes in young adult animals, whilst the human condition associated with NLGN3 mutations appears during the first few years of life. CONCLUSIONS: We describe altered fear responses in Nlgn3(-/y) rats and provide evidence that this is the result of a circuit bias that predisposes flight over freeze responses. Additionally, we demonstrate the first link between PAG dysfunction and ASD/ID. This study provides new insight into potential pathophysiologies leading to anxiety disorders and changes to fear responses in individuals with ASD. En ligne : http://dx.doi.org/10.1186/s13229-022-00511-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=491
in Molecular Autism > 13 (2022) . - 34 p.[article] Imbalance of flight-freeze responses and their cellular correlates in the Nlgn3(-/y) rat model of autism [Texte imprimé et/ou numérique] / Natasha J. ANSTEY, Auteur ; Vijayakumar KAPGAL, Auteur ; Shashank TIWARI, Auteur ; Thomas C. WATSON, Auteur ; Anna K. H. TOFT, Auteur ; Owen R. DANDO, Auteur ; Felicity H. INKPEN, Auteur ; Paul S. BAXTER, Auteur ; Zrinko KOZIĆ, Auteur ; Adam D. JACKSON, Auteur ; Xin HE, Auteur ; Mohammad SARFARAZ NAWAZ, Auteur ; Aiman KAYENAAT, Auteur ; Aditi BHATTACHARYA, Auteur ; David J. A. WYLLIE, Auteur ; Sumantra CHATTARJI, Auteur ; Emma R. WOOD, Auteur ; Oliver HARDT, Auteur ; Peter C. KIND, Auteur . - 34 p.
Langues : Anglais (eng)
in Molecular Autism > 13 (2022) . - 34 p.
Mots-clés : Animals Autistic Disorder/metabolism Fear/physiology Freezing Humans Neurons/physiology Periaqueductal Gray/metabolism Rats Autism Fear Flight Intellectual disability Neuroligin-3 Periaqueductal grey Index. décimale : PER Périodiques Résumé : BACKGROUND: Mutations in the postsynaptic transmembrane protein neuroligin-3 are highly correlative with autism spectrum disorders (ASDs) and intellectual disabilities (IDs). Fear learning is well studied in models of these disorders, however differences in fear response behaviours are often overlooked. We aim to examine fear behaviour and its cellular underpinnings in a rat model of ASD/ID lacking Nlgn3. METHODS: This study uses a range of behavioural tests to understand differences in fear response behaviour in Nlgn3(-/y) rats. Following this, we examined the physiological underpinnings of this in neurons of the periaqueductal grey (PAG), a midbrain area involved in flight-or-freeze responses. We used whole-cell patch-clamp recordings from ex vivo PAG slices, in addition to in vivo local-field potential recordings and electrical stimulation of the PAG in wildtype and Nlgn3(-/y) rats. We analysed behavioural data with two- and three-way ANOVAS and electrophysiological data with generalised linear mixed modelling (GLMM). RESULTS: We observed that, unlike the wildtype, Nlgn3(-/y) rats are more likely to response with flight rather than freezing in threatening situations. Electrophysiological findings were in agreement with these behavioural outcomes. We found in ex vivo slices from Nlgn3(-/y) rats that neurons in dorsal PAG (dPAG) showed intrinsic hyperexcitability compared to wildtype. Similarly, stimulating dPAG in vivo revealed that lower magnitudes sufficed to evoke flight behaviour in Nlgn3(-/y) than wildtype rats, indicating the functional impact of the increased cellular excitability. LIMITATIONS: Our findings do not examine what specific cell type in the PAG is likely responsible for these phenotypes. Furthermore, we have focussed on phenotypes in young adult animals, whilst the human condition associated with NLGN3 mutations appears during the first few years of life. CONCLUSIONS: We describe altered fear responses in Nlgn3(-/y) rats and provide evidence that this is the result of a circuit bias that predisposes flight over freeze responses. Additionally, we demonstrate the first link between PAG dysfunction and ASD/ID. This study provides new insight into potential pathophysiologies leading to anxiety disorders and changes to fear responses in individuals with ASD. En ligne : http://dx.doi.org/10.1186/s13229-022-00511-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=491 Attentional influences on neural processing of biological motion in typically developing children and those on the autism spectrum / Emily J. KNIGHT in Molecular Autism, 13 (2022)
![]()
[article]
Titre : Attentional influences on neural processing of biological motion in typically developing children and those on the autism spectrum Type de document : Texte imprimé et/ou numérique Auteurs : Emily J. KNIGHT, Auteur ; Aaron I. KRAKOWSKI, Auteur ; Edward G. FREEDMAN, Auteur ; John S. BUTLER, Auteur ; Sophie MOLHOLM, Auteur ; John J. FOXE, Auteur Article en page(s) : 33 p. Langues : Anglais (eng) Mots-clés : Adolescent Autism Spectrum Disorder Autistic Disorder Child Cross-Sectional Studies Electroencephalography Humans Social Skills Asd Biological motion Erp Event-related potentials Social cognition Vep Visual evoked potential Index. décimale : PER Périodiques Résumé : BACKGROUND: Biological motion imparts rich information related to the movement, actions, intentions and affective state of others, which can provide foundational support for various aspects of social cognition and behavior. Given that atypical social communication and cognition are hallmark symptoms of autism spectrum disorder (ASD), many have theorized that a potential source of this deficit may lie in dysfunctional neural mechanisms of biological motion processing. Synthesis of existing literature provides some support for biological motion processing deficits in autism spectrum disorder, although high study heterogeneity and inconsistent findings complicate interpretation. Here, we attempted to reconcile some of this residual controversy by investigating a possible modulating role for attention in biological motion processing in ASD. METHODS: We employed high-density electroencephalographic recordings while participants observed point-light displays of upright, inverted and scrambled biological motion under two task conditions to explore spatiotemporal dynamics of intentional and unintentional biological motion processing in children and adolescents with ASD (n=27), comparing them to a control cohort of neurotypical (NT) participants (n=35). RESULTS: Behaviorally, ASD participants were able to discriminate biological motion with similar accuracy to NT controls. However, electrophysiologic investigation revealed reduced automatic selective processing of upright biologic versus scrambled motion stimuli in ASD relative to NT individuals, which was ameliorated when task demands required explicit attention to biological motion. Additionally, we observed distinctive patterns of covariance between visual potentials evoked by biological motion and functional social ability, such that Vineland Adaptive Behavior Scale-Socialization domain scores were differentially associated with biological motion processing in the N1 period in the ASD but not the NT group. LIMITATIONS: The cross-sectional design of this study does not allow us to definitively answer the question of whether developmental differences in attention to biological motion cause disruption in social communication, and the sample was limited to children with average or above cognitive ability. CONCLUSIONS: Together, these data suggest that individuals with ASD are able to discriminate, with explicit attention, biological from non-biological motion but demonstrate diminished automatic neural specificity for biological motion processing, which may have cascading implications for the development of higher-order social cognition. En ligne : http://dx.doi.org/10.1186/s13229-022-00512-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=491
in Molecular Autism > 13 (2022) . - 33 p.[article] Attentional influences on neural processing of biological motion in typically developing children and those on the autism spectrum [Texte imprimé et/ou numérique] / Emily J. KNIGHT, Auteur ; Aaron I. KRAKOWSKI, Auteur ; Edward G. FREEDMAN, Auteur ; John S. BUTLER, Auteur ; Sophie MOLHOLM, Auteur ; John J. FOXE, Auteur . - 33 p.
Langues : Anglais (eng)
in Molecular Autism > 13 (2022) . - 33 p.
Mots-clés : Adolescent Autism Spectrum Disorder Autistic Disorder Child Cross-Sectional Studies Electroencephalography Humans Social Skills Asd Biological motion Erp Event-related potentials Social cognition Vep Visual evoked potential Index. décimale : PER Périodiques Résumé : BACKGROUND: Biological motion imparts rich information related to the movement, actions, intentions and affective state of others, which can provide foundational support for various aspects of social cognition and behavior. Given that atypical social communication and cognition are hallmark symptoms of autism spectrum disorder (ASD), many have theorized that a potential source of this deficit may lie in dysfunctional neural mechanisms of biological motion processing. Synthesis of existing literature provides some support for biological motion processing deficits in autism spectrum disorder, although high study heterogeneity and inconsistent findings complicate interpretation. Here, we attempted to reconcile some of this residual controversy by investigating a possible modulating role for attention in biological motion processing in ASD. METHODS: We employed high-density electroencephalographic recordings while participants observed point-light displays of upright, inverted and scrambled biological motion under two task conditions to explore spatiotemporal dynamics of intentional and unintentional biological motion processing in children and adolescents with ASD (n=27), comparing them to a control cohort of neurotypical (NT) participants (n=35). RESULTS: Behaviorally, ASD participants were able to discriminate biological motion with similar accuracy to NT controls. However, electrophysiologic investigation revealed reduced automatic selective processing of upright biologic versus scrambled motion stimuli in ASD relative to NT individuals, which was ameliorated when task demands required explicit attention to biological motion. Additionally, we observed distinctive patterns of covariance between visual potentials evoked by biological motion and functional social ability, such that Vineland Adaptive Behavior Scale-Socialization domain scores were differentially associated with biological motion processing in the N1 period in the ASD but not the NT group. LIMITATIONS: The cross-sectional design of this study does not allow us to definitively answer the question of whether developmental differences in attention to biological motion cause disruption in social communication, and the sample was limited to children with average or above cognitive ability. CONCLUSIONS: Together, these data suggest that individuals with ASD are able to discriminate, with explicit attention, biological from non-biological motion but demonstrate diminished automatic neural specificity for biological motion processing, which may have cascading implications for the development of higher-order social cognition. En ligne : http://dx.doi.org/10.1186/s13229-022-00512-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=491 Early life sleep disruption potentiates lasting sex-specific changes in behavior in genetically vulnerable Shank3 heterozygous autism model mice / Julia S. LORD in Molecular Autism, 13 (2022)
![]()
[article]
Titre : Early life sleep disruption potentiates lasting sex-specific changes in behavior in genetically vulnerable Shank3 heterozygous autism model mice Type de document : Texte imprimé et/ou numérique Auteurs : Julia S. LORD, Auteur ; Sean M. GAY, Auteur ; Kathryn M. HARPER, Auteur ; Viktoriya D. NIKOLOVA, Auteur ; Kirsten M. SMITH, Auteur ; Sheryl S. MOY, Auteur ; Graham H. DIERING, Auteur Article en page(s) : 35 p. Langues : Anglais (eng) Mots-clés : Animals Autism Spectrum Disorder/genetics Autistic Disorder/genetics Disease Models, Animal Female Male Mice Microfilament Proteins Nerve Tissue Proteins/genetics Sleep Autism spectrum disorder Brain development Shank3 Social behavior Index. décimale : PER Périodiques Résumé : BACKGROUND: Patients with autism spectrum disorder (ASD) experience high rates of sleep disruption beginning early in life; however, the developmental consequences of this disruption are not understood. We examined sleep behavior and the consequences of sleep disruption in developing mice bearing C-terminal truncation mutation in the high-confidence ASD risk gene SHANK3 (Shank3ΔC). We hypothesized that sleep disruption may be an early sign of developmental divergence, and that clinically relevant Shank3(WT/ΔC) mice may be at increased risk of lasting deleterious outcomes following early life sleep disruption. METHODS: We recorded sleep behavior in developing Shank3(ΔC/ΔC), Shank3(WT/ΔC), and wild-type siblings of both sexes using a noninvasive home-cage monitoring system. Separately, litters of Shank3(WT/ΔC) and wild-type littermates were exposed to automated mechanical sleep disruption for 7 days prior to weaning (early life sleep disruption: ELSD) or post-adolescence (PASD) or undisturbed control (CON) conditions. All groups underwent standard behavioral testing as adults. RESULTS: Male and female Shank3(ΔC/ΔC) mice slept significantly less than wild-type and Shank3(WT/ΔC) siblings shortly after weaning, with increasing sleep fragmentation in adolescence, indicating that sleep disruption has a developmental onset in this ASD model. ELSD treatment interacted with genetic vulnerability in Shank3(WT/ΔC) mice, resulting in lasting, sex-specific changes in behavior, whereas wild-type siblings were largely resilient to these effects. Male ELSD Shank3(WT/ΔC) subjects demonstrated significant changes in sociability, sensory processing, and locomotion, while female ELSD Shank3(WT/ΔC) subjects had a significant reduction in risk aversion. CON Shank3(WT/ΔC) mice, PASD mice, and all wild-type mice demonstrated typical behavioral responses in most tests. LIMITATIONS: This study tested the interaction between developmental sleep disruption and genetic vulnerability using a single ASD mouse model: Shank3ΔC (deletion of exon 21). The broader implications of this work should be supported by additional studies using ASD model mice with distinct genetic vulnerabilities. CONCLUSION: Our study shows that sleep disruption during sensitive periods of early life interacts with underlying genetic vulnerability to drive lasting and sex-specific changes in behavior. As individuals progress through maturation, they gain resilience to the lasting effects of sleep disruption. This work highlights developmental sleep disruption as an important vulnerability in ASD susceptibility. En ligne : http://dx.doi.org/10.1186/s13229-022-00514-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=491
in Molecular Autism > 13 (2022) . - 35 p.[article] Early life sleep disruption potentiates lasting sex-specific changes in behavior in genetically vulnerable Shank3 heterozygous autism model mice [Texte imprimé et/ou numérique] / Julia S. LORD, Auteur ; Sean M. GAY, Auteur ; Kathryn M. HARPER, Auteur ; Viktoriya D. NIKOLOVA, Auteur ; Kirsten M. SMITH, Auteur ; Sheryl S. MOY, Auteur ; Graham H. DIERING, Auteur . - 35 p.
Langues : Anglais (eng)
in Molecular Autism > 13 (2022) . - 35 p.
Mots-clés : Animals Autism Spectrum Disorder/genetics Autistic Disorder/genetics Disease Models, Animal Female Male Mice Microfilament Proteins Nerve Tissue Proteins/genetics Sleep Autism spectrum disorder Brain development Shank3 Social behavior Index. décimale : PER Périodiques Résumé : BACKGROUND: Patients with autism spectrum disorder (ASD) experience high rates of sleep disruption beginning early in life; however, the developmental consequences of this disruption are not understood. We examined sleep behavior and the consequences of sleep disruption in developing mice bearing C-terminal truncation mutation in the high-confidence ASD risk gene SHANK3 (Shank3ΔC). We hypothesized that sleep disruption may be an early sign of developmental divergence, and that clinically relevant Shank3(WT/ΔC) mice may be at increased risk of lasting deleterious outcomes following early life sleep disruption. METHODS: We recorded sleep behavior in developing Shank3(ΔC/ΔC), Shank3(WT/ΔC), and wild-type siblings of both sexes using a noninvasive home-cage monitoring system. Separately, litters of Shank3(WT/ΔC) and wild-type littermates were exposed to automated mechanical sleep disruption for 7 days prior to weaning (early life sleep disruption: ELSD) or post-adolescence (PASD) or undisturbed control (CON) conditions. All groups underwent standard behavioral testing as adults. RESULTS: Male and female Shank3(ΔC/ΔC) mice slept significantly less than wild-type and Shank3(WT/ΔC) siblings shortly after weaning, with increasing sleep fragmentation in adolescence, indicating that sleep disruption has a developmental onset in this ASD model. ELSD treatment interacted with genetic vulnerability in Shank3(WT/ΔC) mice, resulting in lasting, sex-specific changes in behavior, whereas wild-type siblings were largely resilient to these effects. Male ELSD Shank3(WT/ΔC) subjects demonstrated significant changes in sociability, sensory processing, and locomotion, while female ELSD Shank3(WT/ΔC) subjects had a significant reduction in risk aversion. CON Shank3(WT/ΔC) mice, PASD mice, and all wild-type mice demonstrated typical behavioral responses in most tests. LIMITATIONS: This study tested the interaction between developmental sleep disruption and genetic vulnerability using a single ASD mouse model: Shank3ΔC (deletion of exon 21). The broader implications of this work should be supported by additional studies using ASD model mice with distinct genetic vulnerabilities. CONCLUSION: Our study shows that sleep disruption during sensitive periods of early life interacts with underlying genetic vulnerability to drive lasting and sex-specific changes in behavior. As individuals progress through maturation, they gain resilience to the lasting effects of sleep disruption. This work highlights developmental sleep disruption as an important vulnerability in ASD susceptibility. En ligne : http://dx.doi.org/10.1186/s13229-022-00514-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=491 Oxytocin impacts top-down and bottom-up social perception in adolescents with ASD: a MEG study of neural connectivity / Adi KORISKY in Molecular Autism, 13 (2022)
![]()
[article]
Titre : Oxytocin impacts top-down and bottom-up social perception in adolescents with ASD: a MEG study of neural connectivity Type de document : Texte imprimé et/ou numérique Auteurs : Adi KORISKY, Auteur ; Ilanit GORDON, Auteur ; Abraham GOLDSTEIN, Auteur Article en page(s) : 36 p. Langues : Anglais (eng) Mots-clés : Administration, Intranasal Animals Autistic Disorder/diagnostic imaging/drug therapy Double-Blind Method Facial Recognition/physiology Magnetic Resonance Imaging/methods Oxytocin/pharmacology Social Perception Autism Connectivity Face perception Gamma Meg Oxytocin personal or financial interests that could influence the study in this paper. Index. décimale : PER Périodiques Résumé : BACKGROUND: In the last decade, accumulative evidence has shown that oxytocin can modulate social perception in typically developed individuals and individuals diagnosed with autism. While several studies show that oxytocin (OT) modulates neural activation in social-related neural regions, the mechanism that underlies OT effects in ASD is not fully known yet. Despite evidence from animal studies on connections between the oxytocinergic system and excitation/inhibition neural balance, the influence of OT on oscillatory responses among individuals with ASD has been rarely examined. To bridge these gaps in knowledge, we investigated the effects of OT on both social and non-social stimuli while focusing on its specific influence on the neural connectivity between three socially related neural regions-the left and right fusiform and the medial frontal cortex. METHODS: Twenty-five adolescents with ASD participated in a wall-established social task during a randomized, double-blind placebo-controlled MEG and OT administration study. Our main task was a social-related task that required the identification of social and non-social-related pictures. We hypothesized that OT would modulate the oscillatory connectivity between three pre-selected regions of interest to be more adaptive to social processing. Specifically, we focused on alpha and gamma bands which are known to play an important role in face processing and top-down/bottom-up balance. RESULTS: Compared to placebo, OT reduced the connectivity between the medial frontal cortex and the fusiform in the low gamma more for social stimuli than for non-social ones, a reduction that was correlated with individuals' performance in the task. Additionally, for both social and non-social stimuli, OT increased the connectivity in the alpha and beta bands. LIMITATIONS: Sample size was determined based on sample sizes previously reported in MEG in clinical populations, especially OT administration studies in combination with neuroimaging in ASD. We were limited in our capability to recruit for such a study, and as such, the sample size was not based on a priori power analysis. Additionally, we limited our analyses to specific neural bands and regions. To validate the current results, future studies may be needed to explore other parameters using whole-brain approaches in larger samples. CONCLUSION: These results suggest that OT influenced social perception by modifying the communication between frontal and posterior regions, an attenuation that potentially impacts both social and non-social early perception. We also show that OT influences differ between top-down and bottom-up processes, depending on the social context. Overall, by showing that OT influences both social-related perception and overall attention during early processing stages, we add new information to the existing understanding of the impact of OT on neural processing in ASD. Furthermore, by highlighting the influence of OT on early perception, we provide new directions for treatments for difficulties in early attentional phases in this population. Trial registration Registered on October 27, 2021-Retrospectively registered, https://clinicaltrials.gov/ct2/show/record/NCT05096676 (details on clinical registration can be found in www. CLINICALTRIAL: gov , unique identifier: NCT05096676 ). En ligne : http://dx.doi.org/10.1186/s13229-022-00513-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=491
in Molecular Autism > 13 (2022) . - 36 p.[article] Oxytocin impacts top-down and bottom-up social perception in adolescents with ASD: a MEG study of neural connectivity [Texte imprimé et/ou numérique] / Adi KORISKY, Auteur ; Ilanit GORDON, Auteur ; Abraham GOLDSTEIN, Auteur . - 36 p.
Langues : Anglais (eng)
in Molecular Autism > 13 (2022) . - 36 p.
Mots-clés : Administration, Intranasal Animals Autistic Disorder/diagnostic imaging/drug therapy Double-Blind Method Facial Recognition/physiology Magnetic Resonance Imaging/methods Oxytocin/pharmacology Social Perception Autism Connectivity Face perception Gamma Meg Oxytocin personal or financial interests that could influence the study in this paper. Index. décimale : PER Périodiques Résumé : BACKGROUND: In the last decade, accumulative evidence has shown that oxytocin can modulate social perception in typically developed individuals and individuals diagnosed with autism. While several studies show that oxytocin (OT) modulates neural activation in social-related neural regions, the mechanism that underlies OT effects in ASD is not fully known yet. Despite evidence from animal studies on connections between the oxytocinergic system and excitation/inhibition neural balance, the influence of OT on oscillatory responses among individuals with ASD has been rarely examined. To bridge these gaps in knowledge, we investigated the effects of OT on both social and non-social stimuli while focusing on its specific influence on the neural connectivity between three socially related neural regions-the left and right fusiform and the medial frontal cortex. METHODS: Twenty-five adolescents with ASD participated in a wall-established social task during a randomized, double-blind placebo-controlled MEG and OT administration study. Our main task was a social-related task that required the identification of social and non-social-related pictures. We hypothesized that OT would modulate the oscillatory connectivity between three pre-selected regions of interest to be more adaptive to social processing. Specifically, we focused on alpha and gamma bands which are known to play an important role in face processing and top-down/bottom-up balance. RESULTS: Compared to placebo, OT reduced the connectivity between the medial frontal cortex and the fusiform in the low gamma more for social stimuli than for non-social ones, a reduction that was correlated with individuals' performance in the task. Additionally, for both social and non-social stimuli, OT increased the connectivity in the alpha and beta bands. LIMITATIONS: Sample size was determined based on sample sizes previously reported in MEG in clinical populations, especially OT administration studies in combination with neuroimaging in ASD. We were limited in our capability to recruit for such a study, and as such, the sample size was not based on a priori power analysis. Additionally, we limited our analyses to specific neural bands and regions. To validate the current results, future studies may be needed to explore other parameters using whole-brain approaches in larger samples. CONCLUSION: These results suggest that OT influenced social perception by modifying the communication between frontal and posterior regions, an attenuation that potentially impacts both social and non-social early perception. We also show that OT influences differ between top-down and bottom-up processes, depending on the social context. Overall, by showing that OT influences both social-related perception and overall attention during early processing stages, we add new information to the existing understanding of the impact of OT on neural processing in ASD. Furthermore, by highlighting the influence of OT on early perception, we provide new directions for treatments for difficulties in early attentional phases in this population. Trial registration Registered on October 27, 2021-Retrospectively registered, https://clinicaltrials.gov/ct2/show/record/NCT05096676 (details on clinical registration can be found in www. CLINICALTRIAL: gov , unique identifier: NCT05096676 ). En ligne : http://dx.doi.org/10.1186/s13229-022-00513-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=491 Salivary testosterone in male and female youth with and without autism spectrum disorder: considerations of development, sex, and diagnosis / Rachael A. MUSCATELLO in Molecular Autism, 13 (2022)
![]()
[article]
Titre : Salivary testosterone in male and female youth with and without autism spectrum disorder: considerations of development, sex, and diagnosis Type de document : Texte imprimé et/ou numérique Auteurs : Rachael A. MUSCATELLO, Auteur ; Emma RAFATJOO, Auteur ; Karan K. MIRPURI, Auteur ; Ahra KIM, Auteur ; Simon VANDEKAR, Auteur ; Blythe A. CORBETT, Auteur Article en page(s) : 37 p. Langues : Anglais (eng) Mots-clés : Autism Spectrum Disorder/diagnosis Autistic Disorder Female Humans Longitudinal Studies Male Sexual Development Testosterone Adolescence Androgen Autism Pubertal development Index. décimale : PER Périodiques Résumé : BACKGROUND: Puberty is characterized by significant physical, hormonal, and psychological changes, which may be especially challenging for individuals with autism spectrum disorder (ASD). Although the etiology of ASD remains uncertain, studies suggest imbalances in hormones, such as testosterone, may modulate the autism phenotype. While differences in fetal and postnatal testosterone have been reported, there is limited literature regarding testosterone variations during adolescence in ASD. We investigated morning salivary testosterone levels in youth with ASD and typical development (TD) to explore hypothesized differences, expecting elevated hormonal levels in ASD compared to TD. METHODS: Youth with ASD (n=140) and TD (n=104), ages 10 to 13Â years, were enrolled as part of a longitudinal study on pubertal development. Pubertal stage was determined by gold standard physical examination, and salivary testosterone was collected in the morning immediately upon waking and 30 min after waking and averaged across 3 days. Diagnostic (ASD/TD) and sex (male/female) differences, as well as interactions with age and puberty, were examined using robust linear mixed effect models. RESULTS: Youth with ASD showed significantly elevated testosterone concentrations compared to same-age TD peers. After the inclusion of natural cubic splines to account for nonlinearity in age, a significant age-by-sex interaction emerged with distinct developmental slopes for males and females. At younger ages, females had higher testosterone, until about 11.5Â years of age, when levels began to plateau, while male testosterone concentrations continued to rapidly increase and surpass females. As expected, more advanced pubertal development was associated with elevated testosterone. In contrast, no significant effect of parent-reported social communication symptoms was observed. LIMITATIONS: Limitations include an unequal sex distribution, non-representative sample (e.g., cognition and race/ethnicity), and inability to examine afternoon/evening testosterone due to detection limits. CONCLUSIONS: Testosterone may play a unique role in the presentation of ASD, especially during periods of dynamic hormonal changes including puberty. Inherent developmental (age, puberty) and sex-based (male, female) factors play a more prominent role in changes in testosterone levels during adolescence. Even so, future research is warranted to determine the differential expression and impact of exposure to excess testosterone during the pubertal transition for youth with ASD. En ligne : http://dx.doi.org/10.1186/s13229-022-00515-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=491
in Molecular Autism > 13 (2022) . - 37 p.[article] Salivary testosterone in male and female youth with and without autism spectrum disorder: considerations of development, sex, and diagnosis [Texte imprimé et/ou numérique] / Rachael A. MUSCATELLO, Auteur ; Emma RAFATJOO, Auteur ; Karan K. MIRPURI, Auteur ; Ahra KIM, Auteur ; Simon VANDEKAR, Auteur ; Blythe A. CORBETT, Auteur . - 37 p.
Langues : Anglais (eng)
in Molecular Autism > 13 (2022) . - 37 p.
Mots-clés : Autism Spectrum Disorder/diagnosis Autistic Disorder Female Humans Longitudinal Studies Male Sexual Development Testosterone Adolescence Androgen Autism Pubertal development Index. décimale : PER Périodiques Résumé : BACKGROUND: Puberty is characterized by significant physical, hormonal, and psychological changes, which may be especially challenging for individuals with autism spectrum disorder (ASD). Although the etiology of ASD remains uncertain, studies suggest imbalances in hormones, such as testosterone, may modulate the autism phenotype. While differences in fetal and postnatal testosterone have been reported, there is limited literature regarding testosterone variations during adolescence in ASD. We investigated morning salivary testosterone levels in youth with ASD and typical development (TD) to explore hypothesized differences, expecting elevated hormonal levels in ASD compared to TD. METHODS: Youth with ASD (n=140) and TD (n=104), ages 10 to 13Â years, were enrolled as part of a longitudinal study on pubertal development. Pubertal stage was determined by gold standard physical examination, and salivary testosterone was collected in the morning immediately upon waking and 30 min after waking and averaged across 3 days. Diagnostic (ASD/TD) and sex (male/female) differences, as well as interactions with age and puberty, were examined using robust linear mixed effect models. RESULTS: Youth with ASD showed significantly elevated testosterone concentrations compared to same-age TD peers. After the inclusion of natural cubic splines to account for nonlinearity in age, a significant age-by-sex interaction emerged with distinct developmental slopes for males and females. At younger ages, females had higher testosterone, until about 11.5Â years of age, when levels began to plateau, while male testosterone concentrations continued to rapidly increase and surpass females. As expected, more advanced pubertal development was associated with elevated testosterone. In contrast, no significant effect of parent-reported social communication symptoms was observed. LIMITATIONS: Limitations include an unequal sex distribution, non-representative sample (e.g., cognition and race/ethnicity), and inability to examine afternoon/evening testosterone due to detection limits. CONCLUSIONS: Testosterone may play a unique role in the presentation of ASD, especially during periods of dynamic hormonal changes including puberty. Inherent developmental (age, puberty) and sex-based (male, female) factors play a more prominent role in changes in testosterone levels during adolescence. Even so, future research is warranted to determine the differential expression and impact of exposure to excess testosterone during the pubertal transition for youth with ASD. En ligne : http://dx.doi.org/10.1186/s13229-022-00515-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=491 Disruption of grin2B, an ASD-associated gene, produces social deficits in zebrafish / Josiah D. ZOODSMA in Molecular Autism, 13 (2022)
![]()
[article]
Titre : Disruption of grin2B, an ASD-associated gene, produces social deficits in zebrafish Type de document : Texte imprimé et/ou numérique Auteurs : Josiah D. ZOODSMA, Auteur ; Emma J. KEEGAN, Auteur ; Gabrielle R. MOODY, Auteur ; Ashwin A. BHANDIWAD, Auteur ; Amalia J. NAPOLI, Auteur ; Harold A. BURGESS, Auteur ; Lonnie P. WOLLMUTH, Auteur ; Howard I. SIROTKIN, Auteur Article en page(s) : 38 p. Langues : Anglais (eng) Mots-clés : Animals Codon, Nonsense Glutamic Acid Neurodevelopmental Disorders/genetics Receptors, N-Methyl-D-Aspartate/genetics Zebrafish/genetics Autism spectrum disorders GluN2B NMDA receptors Social behaviors Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD), like many neurodevelopmental disorders, has complex and varied etiologies. Advances in genome sequencing have identified multiple candidate genes associated with ASD, including dozens of missense and nonsense mutations in the NMDAR subunit GluN2B, encoded by GRIN2B. NMDARs are glutamate-gated ion channels with key synaptic functions in excitatory neurotransmission. How alterations in these proteins impact neurodevelopment is poorly understood, in part because knockouts of GluN2B in rodents are lethal. METHODS: Here, we use CRISPR-Cas9 to generate zebrafish lacking GluN2B (grin2B(-/-)). Using these fish, we run an array of behavioral tests and perform whole-brain larval imaging to assay developmental roles and functions of GluN2B. RESULTS: We demonstrate that zebrafish GluN2B displays similar structural and functional properties to human GluN2B. Zebrafish lacking GluN2B (grin2B(-/-)) surprisingly survive into adulthood. Given the prevalence of social deficits in ASD, we assayed social preference in the grin2B(-/-) fish. Wild-type fish develop a strong social preference by 3Â weeks post fertilization. In contrast, grin2B(-/-) fish at this age exhibit significantly reduced social preference. Notably, the lack of GluN2B does not result in a broad disruption of neurodevelopment, as grin2B(-/-) larvae do not show alterations in spontaneous or photic-evoked movements, are capable of prey capture, and exhibit learning. Whole-brain imaging of grin2B(-/-) larvae revealed reduction of an inhibitory neuron marker in the subpallium, a region linked to ASD in humans, but showed that overall brain size and E/I balance in grin2B(-/-) is comparable to wild type. LIMITATIONS: Zebrafish lacking GluN2B, while useful in studying developmental roles of GluN2B, are unlikely to model nuanced functional alterations of human missense mutations that are not complete loss of function. Additionally, detailed mammalian homologies for larval zebrafish brain subdivisions at the age of whole-brain imaging are not fully resolved. CONCLUSIONS: We demonstrate that zebrafish completely lacking the GluN2B subunit of the NMDAR, unlike rodent models, are viable into adulthood. Notably, they exhibit a highly specific deficit in social behavior. As such, this zebrafish model affords a unique opportunity to study the roles of GluN2B in ASD etiologies and establish a disease-relevant in vivo model for future studies. En ligne : http://dx.doi.org/10.1186/s13229-022-00516-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=491
in Molecular Autism > 13 (2022) . - 38 p.[article] Disruption of grin2B, an ASD-associated gene, produces social deficits in zebrafish [Texte imprimé et/ou numérique] / Josiah D. ZOODSMA, Auteur ; Emma J. KEEGAN, Auteur ; Gabrielle R. MOODY, Auteur ; Ashwin A. BHANDIWAD, Auteur ; Amalia J. NAPOLI, Auteur ; Harold A. BURGESS, Auteur ; Lonnie P. WOLLMUTH, Auteur ; Howard I. SIROTKIN, Auteur . - 38 p.
Langues : Anglais (eng)
in Molecular Autism > 13 (2022) . - 38 p.
Mots-clés : Animals Codon, Nonsense Glutamic Acid Neurodevelopmental Disorders/genetics Receptors, N-Methyl-D-Aspartate/genetics Zebrafish/genetics Autism spectrum disorders GluN2B NMDA receptors Social behaviors Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD), like many neurodevelopmental disorders, has complex and varied etiologies. Advances in genome sequencing have identified multiple candidate genes associated with ASD, including dozens of missense and nonsense mutations in the NMDAR subunit GluN2B, encoded by GRIN2B. NMDARs are glutamate-gated ion channels with key synaptic functions in excitatory neurotransmission. How alterations in these proteins impact neurodevelopment is poorly understood, in part because knockouts of GluN2B in rodents are lethal. METHODS: Here, we use CRISPR-Cas9 to generate zebrafish lacking GluN2B (grin2B(-/-)). Using these fish, we run an array of behavioral tests and perform whole-brain larval imaging to assay developmental roles and functions of GluN2B. RESULTS: We demonstrate that zebrafish GluN2B displays similar structural and functional properties to human GluN2B. Zebrafish lacking GluN2B (grin2B(-/-)) surprisingly survive into adulthood. Given the prevalence of social deficits in ASD, we assayed social preference in the grin2B(-/-) fish. Wild-type fish develop a strong social preference by 3Â weeks post fertilization. In contrast, grin2B(-/-) fish at this age exhibit significantly reduced social preference. Notably, the lack of GluN2B does not result in a broad disruption of neurodevelopment, as grin2B(-/-) larvae do not show alterations in spontaneous or photic-evoked movements, are capable of prey capture, and exhibit learning. Whole-brain imaging of grin2B(-/-) larvae revealed reduction of an inhibitory neuron marker in the subpallium, a region linked to ASD in humans, but showed that overall brain size and E/I balance in grin2B(-/-) is comparable to wild type. LIMITATIONS: Zebrafish lacking GluN2B, while useful in studying developmental roles of GluN2B, are unlikely to model nuanced functional alterations of human missense mutations that are not complete loss of function. Additionally, detailed mammalian homologies for larval zebrafish brain subdivisions at the age of whole-brain imaging are not fully resolved. CONCLUSIONS: We demonstrate that zebrafish completely lacking the GluN2B subunit of the NMDAR, unlike rodent models, are viable into adulthood. Notably, they exhibit a highly specific deficit in social behavior. As such, this zebrafish model affords a unique opportunity to study the roles of GluN2B in ASD etiologies and establish a disease-relevant in vivo model for future studies. En ligne : http://dx.doi.org/10.1186/s13229-022-00516-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=491 Atypical gaze patterns in autistic adults are heterogeneous across but reliable within individuals / Umit KELES in Molecular Autism, 13 (2022)
![]()
[article]
Titre : Atypical gaze patterns in autistic adults are heterogeneous across but reliable within individuals Type de document : Texte imprimé et/ou numérique Auteurs : Umit KELES, Auteur ; Dorit KLIEMANN, Auteur ; Lisa BYRGE, Auteur ; Heini SAARIMAKI, Auteur ; Lynn K. PAUL, Auteur ; Daniel P. KENNEDY, Auteur ; Ralph ADOLPHS, Auteur Article en page(s) : 39 p. Langues : Anglais (eng) Mots-clés : Adult Autism Spectrum Disorder/diagnosis Autistic Disorder/diagnosis Fixation, Ocular Humans Autism Eye tracking Heterogeneity Individual differences Videos Index. décimale : PER Périodiques Résumé : BACKGROUND: Across behavioral studies, autistic individuals show greater variability than typically developing individuals. However, it remains unknown to what extent this variability arises from heterogeneity across individuals, or from unreliability within individuals. Here, we focus on eye tracking, which provides rich dependent measures that have been used extensively in studies of autism. Autistic individuals have an atypical gaze onto both static visual images and dynamic videos that could be leveraged for diagnostic purposes if the above open question could be addressed. METHODS: We tested three competing hypotheses: (1) that gaze patterns of autistic individuals are less reliable or noisier than those of controls, (2) that atypical gaze patterns are individually reliable but heterogeneous across autistic individuals, or (3) that atypical gaze patterns are individually reliable and also homogeneous among autistic individuals. We collected desktop-based eye tracking data from two different full-length television sitcom episodes, at two independent sites (Caltech and Indiana University), in a total of over 150 adult participants (N=48 autistic individuals with IQ in the normal range, 105 controls) and quantified gaze onto features of the videos using automated computer vision-based feature extraction. RESULTS: We found support for the second of these hypotheses. Autistic people and controls showed equivalently reliable gaze onto specific features of videos, such as faces, so much so that individuals could be identified significantly above chance using a fingerprinting approach from video epochs as short as 2Â min. However, classification of participants into diagnostic groups based on their eye tracking data failed to produce clear group classifications, due to heterogeneity in the autistic group. LIMITATIONS: Three limitations are the relatively small sample size, assessment across only two videos (from the same television series), and the absence of other dependent measures (e.g., neuroimaging or genetics) that might have revealed individual-level variability that was not evident with eye tracking. Future studies should expand to larger samples across longer longitudinal epochs, an aim that is now becoming feasible with Internet- and phone-based eye tracking. CONCLUSIONS: These findings pave the way for the investigation of autism subtypes, and for elucidating the specific visual features that best discriminate gaze patterns-directions that will also combine with and inform neuroimaging and genetic studies of this complex disorder. En ligne : http://dx.doi.org/10.1186/s13229-022-00517-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=491
in Molecular Autism > 13 (2022) . - 39 p.[article] Atypical gaze patterns in autistic adults are heterogeneous across but reliable within individuals [Texte imprimé et/ou numérique] / Umit KELES, Auteur ; Dorit KLIEMANN, Auteur ; Lisa BYRGE, Auteur ; Heini SAARIMAKI, Auteur ; Lynn K. PAUL, Auteur ; Daniel P. KENNEDY, Auteur ; Ralph ADOLPHS, Auteur . - 39 p.
Langues : Anglais (eng)
in Molecular Autism > 13 (2022) . - 39 p.
Mots-clés : Adult Autism Spectrum Disorder/diagnosis Autistic Disorder/diagnosis Fixation, Ocular Humans Autism Eye tracking Heterogeneity Individual differences Videos Index. décimale : PER Périodiques Résumé : BACKGROUND: Across behavioral studies, autistic individuals show greater variability than typically developing individuals. However, it remains unknown to what extent this variability arises from heterogeneity across individuals, or from unreliability within individuals. Here, we focus on eye tracking, which provides rich dependent measures that have been used extensively in studies of autism. Autistic individuals have an atypical gaze onto both static visual images and dynamic videos that could be leveraged for diagnostic purposes if the above open question could be addressed. METHODS: We tested three competing hypotheses: (1) that gaze patterns of autistic individuals are less reliable or noisier than those of controls, (2) that atypical gaze patterns are individually reliable but heterogeneous across autistic individuals, or (3) that atypical gaze patterns are individually reliable and also homogeneous among autistic individuals. We collected desktop-based eye tracking data from two different full-length television sitcom episodes, at two independent sites (Caltech and Indiana University), in a total of over 150 adult participants (N=48 autistic individuals with IQ in the normal range, 105 controls) and quantified gaze onto features of the videos using automated computer vision-based feature extraction. RESULTS: We found support for the second of these hypotheses. Autistic people and controls showed equivalently reliable gaze onto specific features of videos, such as faces, so much so that individuals could be identified significantly above chance using a fingerprinting approach from video epochs as short as 2Â min. However, classification of participants into diagnostic groups based on their eye tracking data failed to produce clear group classifications, due to heterogeneity in the autistic group. LIMITATIONS: Three limitations are the relatively small sample size, assessment across only two videos (from the same television series), and the absence of other dependent measures (e.g., neuroimaging or genetics) that might have revealed individual-level variability that was not evident with eye tracking. Future studies should expand to larger samples across longer longitudinal epochs, an aim that is now becoming feasible with Internet- and phone-based eye tracking. CONCLUSIONS: These findings pave the way for the investigation of autism subtypes, and for elucidating the specific visual features that best discriminate gaze patterns-directions that will also combine with and inform neuroimaging and genetic studies of this complex disorder. En ligne : http://dx.doi.org/10.1186/s13229-022-00517-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=491 Enhanced fear limits behavioral flexibility in Shank2-deficient mice / Miru YUN in Molecular Autism, 13 (2022)
![]()
[article]
Titre : Enhanced fear limits behavioral flexibility in Shank2-deficient mice Type de document : Texte imprimé et/ou numérique Auteurs : Miru YUN, Auteur ; Eunjoon KIM, Auteur ; Min Whan JUNG, Auteur Article en page(s) : 40 p. Langues : Anglais (eng) Mots-clés : Animals Autism Spectrum Disorder/genetics/psychology Conditioning, Classical Disease Models, Animal Fear Male Mice Mice, Knockout Nerve Tissue Proteins/genetics Water Classical conditioning Reversal learning Shank2 Index. décimale : PER Périodiques Résumé : BACKGROUND: A core symptom of autism spectrum disorder (ASD) is repetitive and restrictive patterns of behavior. Cognitive inflexibility has been proposed as a potential basis for these symptoms of ASD. More generally, behavioral inflexibility has been proposed to underlie repetitive and restrictive behavior in ASD. Here, we investigated whether and how behavioral flexibility is compromised in a widely used animal model of ASD. METHODS: We compared the behavioral performance of Shank2-knockout mice and wild-type littermates in reversal learning employing a probabilistic classical trace conditioning paradigm. A conditioned stimulus (odor) was paired with an unconditioned appetitive (water, 6Â Âul) or aversive (air puff) stimulus in a probabilistic manner. We also compared air puff-induced eye closure responses of Shank2-knockout and wild-type mice. RESULTS: Male, but not female, Shank2-knockout mice showed impaired reversal learning when the expected outcomes consisted of a water reward and a strong air puff. Moreover, male, but not female, Shank2-knockout mice showed stronger anticipatory eye closure responses to the air puff compared to wild-type littermates, raising the possibility that the impairment might reflect enhanced fear. In support of this contention, male Shank2-knockout mice showed intact reversal learning when the strong air puff was replaced with a mild air puff and when the expected outcomes consisted of only rewards. LIMITATIONS: We examined behavioral flexibility in one behavioral task (reversal learning in a probabilistic classical trace conditioning paradigm) using one ASD mouse model (Shank2-knockout mice). Thus, future work is needed to clarify the extent to which our findings (that enhanced fear limits behavioral flexibility in ASD) can explain the behavioral inflexibility associated with ASD. Also, we examined only the relationship between fear and behavioral flexibility, leaving open the question of whether abnormalities in processes other than fear contribute to behavioral inflexibility in ASD. Finally, the neurobiological mechanisms linking Shank2-knockout and enhanced fear remain to be elucidated. CONCLUSIONS: Our results indicate that enhanced fear suppresses reversal learning in the presence of an intact capability to learn cue-outcome contingency changes in Shank2-knockout mice. Our findings suggest that behavioral flexibility might be seriously limited by abnormal emotional responses in ASD. En ligne : http://dx.doi.org/10.1186/s13229-022-00518-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=491
in Molecular Autism > 13 (2022) . - 40 p.[article] Enhanced fear limits behavioral flexibility in Shank2-deficient mice [Texte imprimé et/ou numérique] / Miru YUN, Auteur ; Eunjoon KIM, Auteur ; Min Whan JUNG, Auteur . - 40 p.
Langues : Anglais (eng)
in Molecular Autism > 13 (2022) . - 40 p.
Mots-clés : Animals Autism Spectrum Disorder/genetics/psychology Conditioning, Classical Disease Models, Animal Fear Male Mice Mice, Knockout Nerve Tissue Proteins/genetics Water Classical conditioning Reversal learning Shank2 Index. décimale : PER Périodiques Résumé : BACKGROUND: A core symptom of autism spectrum disorder (ASD) is repetitive and restrictive patterns of behavior. Cognitive inflexibility has been proposed as a potential basis for these symptoms of ASD. More generally, behavioral inflexibility has been proposed to underlie repetitive and restrictive behavior in ASD. Here, we investigated whether and how behavioral flexibility is compromised in a widely used animal model of ASD. METHODS: We compared the behavioral performance of Shank2-knockout mice and wild-type littermates in reversal learning employing a probabilistic classical trace conditioning paradigm. A conditioned stimulus (odor) was paired with an unconditioned appetitive (water, 6Â Âul) or aversive (air puff) stimulus in a probabilistic manner. We also compared air puff-induced eye closure responses of Shank2-knockout and wild-type mice. RESULTS: Male, but not female, Shank2-knockout mice showed impaired reversal learning when the expected outcomes consisted of a water reward and a strong air puff. Moreover, male, but not female, Shank2-knockout mice showed stronger anticipatory eye closure responses to the air puff compared to wild-type littermates, raising the possibility that the impairment might reflect enhanced fear. In support of this contention, male Shank2-knockout mice showed intact reversal learning when the strong air puff was replaced with a mild air puff and when the expected outcomes consisted of only rewards. LIMITATIONS: We examined behavioral flexibility in one behavioral task (reversal learning in a probabilistic classical trace conditioning paradigm) using one ASD mouse model (Shank2-knockout mice). Thus, future work is needed to clarify the extent to which our findings (that enhanced fear limits behavioral flexibility in ASD) can explain the behavioral inflexibility associated with ASD. Also, we examined only the relationship between fear and behavioral flexibility, leaving open the question of whether abnormalities in processes other than fear contribute to behavioral inflexibility in ASD. Finally, the neurobiological mechanisms linking Shank2-knockout and enhanced fear remain to be elucidated. CONCLUSIONS: Our results indicate that enhanced fear suppresses reversal learning in the presence of an intact capability to learn cue-outcome contingency changes in Shank2-knockout mice. Our findings suggest that behavioral flexibility might be seriously limited by abnormal emotional responses in ASD. En ligne : http://dx.doi.org/10.1186/s13229-022-00518-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=491 Beyond the three-chamber test: toward a multimodal and objective assessment of social behavior in rodents / Renad JABARIN in Molecular Autism, 13 (2022)
![]()
[article]
Titre : Beyond the three-chamber test: toward a multimodal and objective assessment of social behavior in rodents Type de document : Texte imprimé et/ou numérique Auteurs : Renad JABARIN, Auteur ; Shai NETSER, Auteur ; Shlomo WAGNER, Auteur Article en page(s) : 41 p. Langues : Anglais (eng) Mots-clés : Animals Humans Rodentia Autism Spectrum Disorder Social Behavior Behavior, Animal Emotions Animal models Autism spectrum disorder Behavioral phenotyping Emotional states Social vocalizations Three-chamber test Index. décimale : PER Périodiques Résumé : MAIN: In recent years, substantial advances in social neuroscience have been realized, including the generation of numerous rodent models of autism spectrum disorder. Still, it can be argued that those methods currently being used to analyze animal social behavior create a bottleneck that significantly slows down progress in this field. Indeed, the bulk of research still relies on a small number of simple behavioral paradigms, the results of which are assessed without considering behavioral dynamics. Moreover, only few variables are examined in each paradigm, thus overlooking a significant portion of the complexity that characterizes social interaction between two conspecifics, subsequently hindering our understanding of the neural mechanisms governing different aspects of social behavior. We further demonstrate these constraints by discussing the most commonly used paradigm for assessing rodent social behavior, the three-chamber test. We also point to the fact that although emotions greatly influence human social behavior, we lack reliable means for assessing the emotional state of animals during social tasks. As such, we also discuss current evidence supporting the existence of pro-social emotions and emotional cognition in animal models. We further suggest that adequate social behavior analysis requires a novel multimodal approach that employs automated and simultaneous measurements of multiple behavioral and physiological variables at high temporal resolution in socially interacting animals. We accordingly describe several computerized systems and computational tools for acquiring and analyzing such measurements. Finally, we address several behavioral and physiological variables that can be used to assess socio-emotional states in animal models and thus elucidate intricacies of social behavior so as to attain deeper insight into the brain mechanisms that mediate such behaviors. CONCLUSIONS: In summary, we suggest that combining automated multimodal measurements with machine-learning algorithms will help define socio-emotional states and determine their dynamics during various types of social tasks, thus enabling a more thorough understanding of the complexity of social behavior. En ligne : http://dx.doi.org/10.1186/s13229-022-00521-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=491
in Molecular Autism > 13 (2022) . - 41 p.[article] Beyond the three-chamber test: toward a multimodal and objective assessment of social behavior in rodents [Texte imprimé et/ou numérique] / Renad JABARIN, Auteur ; Shai NETSER, Auteur ; Shlomo WAGNER, Auteur . - 41 p.
Langues : Anglais (eng)
in Molecular Autism > 13 (2022) . - 41 p.
Mots-clés : Animals Humans Rodentia Autism Spectrum Disorder Social Behavior Behavior, Animal Emotions Animal models Autism spectrum disorder Behavioral phenotyping Emotional states Social vocalizations Three-chamber test Index. décimale : PER Périodiques Résumé : MAIN: In recent years, substantial advances in social neuroscience have been realized, including the generation of numerous rodent models of autism spectrum disorder. Still, it can be argued that those methods currently being used to analyze animal social behavior create a bottleneck that significantly slows down progress in this field. Indeed, the bulk of research still relies on a small number of simple behavioral paradigms, the results of which are assessed without considering behavioral dynamics. Moreover, only few variables are examined in each paradigm, thus overlooking a significant portion of the complexity that characterizes social interaction between two conspecifics, subsequently hindering our understanding of the neural mechanisms governing different aspects of social behavior. We further demonstrate these constraints by discussing the most commonly used paradigm for assessing rodent social behavior, the three-chamber test. We also point to the fact that although emotions greatly influence human social behavior, we lack reliable means for assessing the emotional state of animals during social tasks. As such, we also discuss current evidence supporting the existence of pro-social emotions and emotional cognition in animal models. We further suggest that adequate social behavior analysis requires a novel multimodal approach that employs automated and simultaneous measurements of multiple behavioral and physiological variables at high temporal resolution in socially interacting animals. We accordingly describe several computerized systems and computational tools for acquiring and analyzing such measurements. Finally, we address several behavioral and physiological variables that can be used to assess socio-emotional states in animal models and thus elucidate intricacies of social behavior so as to attain deeper insight into the brain mechanisms that mediate such behaviors. CONCLUSIONS: In summary, we suggest that combining automated multimodal measurements with machine-learning algorithms will help define socio-emotional states and determine their dynamics during various types of social tasks, thus enabling a more thorough understanding of the complexity of social behavior. En ligne : http://dx.doi.org/10.1186/s13229-022-00521-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=491 Predictability modulates neural response to eye contact in ASD / Adam J. NAPLES in Molecular Autism, 13 (2022)
![]()
[article]
Titre : Predictability modulates neural response to eye contact in ASD Type de document : Texte imprimé et/ou numérique Auteurs : Adam J. NAPLES, Auteur ; Jennifer H. FOSS-FEIG, Auteur ; Julie M. WOLF, Auteur ; Vinod H. SRIHARI, Auteur ; James C. MCPARTLAND, Auteur Article en page(s) : 42 p. Langues : Anglais (eng) Mots-clés : Adult Humans Female Autism Spectrum Disorder Autistic Disorder Interpersonal Relations Nonverbal Communication Autism Erp Eye tracking N170 P300 Social neuroscience Health, and BlackThorn Therapeutics, has received research funding from Janssen Research and Development, serves on the Scientific Advisory Boards of Pastorus and Modern Clinics, and receives royalties from Guilford Press, Lambert, and Springer. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Index. décimale : PER Périodiques Résumé : BACKGROUND: Deficits in establishing and maintaining eye-contact are early and persistent vulnerabilities of autism spectrum disorder (ASD), and the neural bases of these deficits remain elusive. A promising hypothesis is that social features of autism may reflect difficulties in making predictions about the social world under conditions of uncertainty. However, no research in ASD has examined how predictability impacts the neural processing of eye-contact in naturalistic interpersonal interactions. METHOD: We used eye tracking to facilitate an interactive social simulation wherein onscreen faces would establish eye-contact when the participant looked at them. In Experiment One, receipt of eye-contact was unpredictable; in Experiment Two, receipt of eye-contact was predictable. Neural response to eye-contact was measured via the N170 and P300 event-related potentials (ERPs). Experiment One included 23 ASD and 46 typically developing (TD) adult participants. Experiment Two included 25 ASD and 43 TD adult participants. RESULTS: When receipt of eye-contact was unpredictable, individuals with ASD showed increased N170 and increased, but non-specific, P300 responses. The magnitude of the N170 responses correlated with measures of sensory and anxiety symptomology, such that increased response to eye-contact was associated with increased symptomology. However, when receipt of eye-contact was predictable, individuals with ASD, relative to controls, exhibited slower N170s and no differences in the amplitude of N170 or P300. LIMITATIONS: Our ASD sample was composed of adults with IQ> 70 and included only four autistic women. Thus, further research is needed to evaluate how these results generalize across the spectrum of age, sex, and cognitive ability. Additionally, as analyses were exploratory, some findings failed to survive false-discovery rate adjustment. CONCLUSIONS: Neural response to eye-contact in ASD ranged from attenuated to hypersensitive depending on the predictability of the social context. These findings suggest that the vulnerabilities in eye-contact during social interactions in ASD may arise from differences in anticipation and expectation of eye-contact in addition to the perception of gaze alone. En ligne : http://dx.doi.org/10.1186/s13229-022-00519-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=491
in Molecular Autism > 13 (2022) . - 42 p.[article] Predictability modulates neural response to eye contact in ASD [Texte imprimé et/ou numérique] / Adam J. NAPLES, Auteur ; Jennifer H. FOSS-FEIG, Auteur ; Julie M. WOLF, Auteur ; Vinod H. SRIHARI, Auteur ; James C. MCPARTLAND, Auteur . - 42 p.
Langues : Anglais (eng)
in Molecular Autism > 13 (2022) . - 42 p.
Mots-clés : Adult Humans Female Autism Spectrum Disorder Autistic Disorder Interpersonal Relations Nonverbal Communication Autism Erp Eye tracking N170 P300 Social neuroscience Health, and BlackThorn Therapeutics, has received research funding from Janssen Research and Development, serves on the Scientific Advisory Boards of Pastorus and Modern Clinics, and receives royalties from Guilford Press, Lambert, and Springer. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Index. décimale : PER Périodiques Résumé : BACKGROUND: Deficits in establishing and maintaining eye-contact are early and persistent vulnerabilities of autism spectrum disorder (ASD), and the neural bases of these deficits remain elusive. A promising hypothesis is that social features of autism may reflect difficulties in making predictions about the social world under conditions of uncertainty. However, no research in ASD has examined how predictability impacts the neural processing of eye-contact in naturalistic interpersonal interactions. METHOD: We used eye tracking to facilitate an interactive social simulation wherein onscreen faces would establish eye-contact when the participant looked at them. In Experiment One, receipt of eye-contact was unpredictable; in Experiment Two, receipt of eye-contact was predictable. Neural response to eye-contact was measured via the N170 and P300 event-related potentials (ERPs). Experiment One included 23 ASD and 46 typically developing (TD) adult participants. Experiment Two included 25 ASD and 43 TD adult participants. RESULTS: When receipt of eye-contact was unpredictable, individuals with ASD showed increased N170 and increased, but non-specific, P300 responses. The magnitude of the N170 responses correlated with measures of sensory and anxiety symptomology, such that increased response to eye-contact was associated with increased symptomology. However, when receipt of eye-contact was predictable, individuals with ASD, relative to controls, exhibited slower N170s and no differences in the amplitude of N170 or P300. LIMITATIONS: Our ASD sample was composed of adults with IQ> 70 and included only four autistic women. Thus, further research is needed to evaluate how these results generalize across the spectrum of age, sex, and cognitive ability. Additionally, as analyses were exploratory, some findings failed to survive false-discovery rate adjustment. CONCLUSIONS: Neural response to eye-contact in ASD ranged from attenuated to hypersensitive depending on the predictability of the social context. These findings suggest that the vulnerabilities in eye-contact during social interactions in ASD may arise from differences in anticipation and expectation of eye-contact in addition to the perception of gaze alone. En ligne : http://dx.doi.org/10.1186/s13229-022-00519-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=491 Facial expression recognition is linked to clinical and neurofunctional differences in autism / Hannah MEYER-LINDENBERG in Molecular Autism, 13 (2022)
![]()
[article]
Titre : Facial expression recognition is linked to clinical and neurofunctional differences in autism Type de document : Texte imprimé et/ou numérique Auteurs : Hannah MEYER-LINDENBERG, Auteur ; Carolin MOESSNANG, Auteur ; Bethany OAKLEY, Auteur ; Jumana AHMAD, Auteur ; Luke MASON, Auteur ; Emily J. H. JONES, Auteur ; Hannah L. HAYWARD, Auteur ; Jennifer COOKE, Auteur ; Daisy CRAWLEY, Auteur ; Rosemary HOLT, Auteur ; Julian TILLMANN, Auteur ; Tony CHARMAN, Auteur ; Simon BARON-COHEN, Auteur ; Tobias BANASCHEWSKI, Auteur ; Christian BECKMANN, Auteur ; Heike TOST, Auteur ; Andreas MEYER-LINDENBERG, Auteur ; Jan K. BUITELAAR, Auteur ; Declan G. MURPHY, Auteur ; Michael J. BRAMMER, Auteur ; Eva LOTH, Auteur Article en page(s) : 43 p. Langues : Anglais (eng) Mots-clés : Humans Facial Recognition Autistic Disorder/diagnostic imaging Emotions Magnetic Resonance Imaging/methods Biomarkers Autism Spectrum Disorder Facial Expression Autism Autism spectrum disorder Clustering analysis Development Facial expression recognition Multi-site Social brain Stratification biomarkers fMRI consultant to F. Hoffmann-La Roche Ltd. and Servier and has received royalties from Sage Publications and Guilford Publications. TB served in an advisory or consultancy role for Lundbeck, Medice, Neurim Pharmaceuticals, Oberberg GmbH, Takeda, and Infectopharm. He received conference support or speaker’s fee by Lilly, Medice, and Takeda. He received royalties from Hogrefe, Kohlhammer, CIP Medien, Oxford University Press the present work is unrelated to these relationships. AM-L has received consultant fees in the past two years from Boehringer Ingelheim, Elsevier, Lundbeck Int. Neuroscience Foundation, Lundbeck AS, The Wolfson Foundation, Thieme Verlag, Sage Therapeutics, von Behring Stiftung, Fondation FondaMental, Janssen-Cilag GmbH, MedinCell, Brain Mind Institute, CISSN. Furthermore, he has received speaker fees from Italian Society of biological Psychiatry, Merz-Stiftung, Forum Werkstatt Karlsruhe, Lundbeck SAS France, BAG Psychiatrie Oberbayern. JB has been in the past 3 years a consultant to/member of advisory board of/and/or speaker for Takeda/Shire, Roche, Medice, Angelini, Janssen, and Servier. He is not an employee of any of these companies, and not a stock shareholder of any of these companies. He has no other financial or material support, including expert testimony, patents, royalties. EL is an Associate Editor at Molecular Autism. DM has been paid for advisory board work by F. Hoffmann-La Roche Ltd. and Servier, and for editorial work by Springer. The other authors declare that they have no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Difficulties in social communication are a defining clinical feature of autism. However, the underlying neurobiological heterogeneity has impeded targeted therapies and requires new approaches to identifying clinically relevant bio-behavioural subgroups. In the largest autism cohort to date, we comprehensively examined difficulties in facial expression recognition, a key process in social communication, as a bio-behavioural stratification biomarker, and validated them against clinical features and neurofunctional responses. METHODS: Between 255 and 488 participants aged 6-30 years with autism, typical development and/or mild intellectual disability completed the Karolinska Directed Emotional Faces task, the Reading the Mind in the Eyes Task and/or the Films Expression Task. We first examined mean-group differences on each test. Then, we used a novel intersection approach that compares two centroid and connectivity-based clustering methods to derive subgroups based on the combined performance across the three tasks. Measures and subgroups were then related to clinical features and neurofunctional differences measured using fMRI during a fearful face-matching task. RESULTS: We found significant mean-group differences on each expression recognition test. However, cluster analyses showed that these were driven by a low-performing autistic subgroup (~ 30% of autistic individuals who performed below 2SDs of the neurotypical mean on at least one test), while a larger subgroup (~ 70%) performed within 1SD on at least 2 tests. The low-performing subgroup also had on average significantly more social communication difficulties and lower activation in the amygdala and fusiform gyrus than the high-performing subgroup. LIMITATIONS: Findings of autism expression recognition subgroups and their characteristics require independent replication. This is currently not possible, as there is no other existing dataset that includes all relevant measures. However, we demonstrated high internal robustness (91.6%) of findings between two clustering methods with fundamentally different assumptions, which is a critical pre-condition for independent replication. CONCLUSIONS: We identified a subgroup of autistic individuals with expression recognition difficulties and showed that this related to clinical and neurobiological characteristics. If replicated, expression recognition may serve as bio-behavioural stratification biomarker and aid in the development of targeted interventions for a subgroup of autistic individuals. En ligne : http://dx.doi.org/10.1186/s13229-022-00520-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=491
in Molecular Autism > 13 (2022) . - 43 p.[article] Facial expression recognition is linked to clinical and neurofunctional differences in autism [Texte imprimé et/ou numérique] / Hannah MEYER-LINDENBERG, Auteur ; Carolin MOESSNANG, Auteur ; Bethany OAKLEY, Auteur ; Jumana AHMAD, Auteur ; Luke MASON, Auteur ; Emily J. H. JONES, Auteur ; Hannah L. HAYWARD, Auteur ; Jennifer COOKE, Auteur ; Daisy CRAWLEY, Auteur ; Rosemary HOLT, Auteur ; Julian TILLMANN, Auteur ; Tony CHARMAN, Auteur ; Simon BARON-COHEN, Auteur ; Tobias BANASCHEWSKI, Auteur ; Christian BECKMANN, Auteur ; Heike TOST, Auteur ; Andreas MEYER-LINDENBERG, Auteur ; Jan K. BUITELAAR, Auteur ; Declan G. MURPHY, Auteur ; Michael J. BRAMMER, Auteur ; Eva LOTH, Auteur . - 43 p.
Langues : Anglais (eng)
in Molecular Autism > 13 (2022) . - 43 p.
Mots-clés : Humans Facial Recognition Autistic Disorder/diagnostic imaging Emotions Magnetic Resonance Imaging/methods Biomarkers Autism Spectrum Disorder Facial Expression Autism Autism spectrum disorder Clustering analysis Development Facial expression recognition Multi-site Social brain Stratification biomarkers fMRI consultant to F. Hoffmann-La Roche Ltd. and Servier and has received royalties from Sage Publications and Guilford Publications. TB served in an advisory or consultancy role for Lundbeck, Medice, Neurim Pharmaceuticals, Oberberg GmbH, Takeda, and Infectopharm. He received conference support or speaker’s fee by Lilly, Medice, and Takeda. He received royalties from Hogrefe, Kohlhammer, CIP Medien, Oxford University Press the present work is unrelated to these relationships. AM-L has received consultant fees in the past two years from Boehringer Ingelheim, Elsevier, Lundbeck Int. Neuroscience Foundation, Lundbeck AS, The Wolfson Foundation, Thieme Verlag, Sage Therapeutics, von Behring Stiftung, Fondation FondaMental, Janssen-Cilag GmbH, MedinCell, Brain Mind Institute, CISSN. Furthermore, he has received speaker fees from Italian Society of biological Psychiatry, Merz-Stiftung, Forum Werkstatt Karlsruhe, Lundbeck SAS France, BAG Psychiatrie Oberbayern. JB has been in the past 3 years a consultant to/member of advisory board of/and/or speaker for Takeda/Shire, Roche, Medice, Angelini, Janssen, and Servier. He is not an employee of any of these companies, and not a stock shareholder of any of these companies. He has no other financial or material support, including expert testimony, patents, royalties. EL is an Associate Editor at Molecular Autism. DM has been paid for advisory board work by F. Hoffmann-La Roche Ltd. and Servier, and for editorial work by Springer. The other authors declare that they have no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Difficulties in social communication are a defining clinical feature of autism. However, the underlying neurobiological heterogeneity has impeded targeted therapies and requires new approaches to identifying clinically relevant bio-behavioural subgroups. In the largest autism cohort to date, we comprehensively examined difficulties in facial expression recognition, a key process in social communication, as a bio-behavioural stratification biomarker, and validated them against clinical features and neurofunctional responses. METHODS: Between 255 and 488 participants aged 6-30 years with autism, typical development and/or mild intellectual disability completed the Karolinska Directed Emotional Faces task, the Reading the Mind in the Eyes Task and/or the Films Expression Task. We first examined mean-group differences on each test. Then, we used a novel intersection approach that compares two centroid and connectivity-based clustering methods to derive subgroups based on the combined performance across the three tasks. Measures and subgroups were then related to clinical features and neurofunctional differences measured using fMRI during a fearful face-matching task. RESULTS: We found significant mean-group differences on each expression recognition test. However, cluster analyses showed that these were driven by a low-performing autistic subgroup (~ 30% of autistic individuals who performed below 2SDs of the neurotypical mean on at least one test), while a larger subgroup (~ 70%) performed within 1SD on at least 2 tests. The low-performing subgroup also had on average significantly more social communication difficulties and lower activation in the amygdala and fusiform gyrus than the high-performing subgroup. LIMITATIONS: Findings of autism expression recognition subgroups and their characteristics require independent replication. This is currently not possible, as there is no other existing dataset that includes all relevant measures. However, we demonstrated high internal robustness (91.6%) of findings between two clustering methods with fundamentally different assumptions, which is a critical pre-condition for independent replication. CONCLUSIONS: We identified a subgroup of autistic individuals with expression recognition difficulties and showed that this related to clinical and neurobiological characteristics. If replicated, expression recognition may serve as bio-behavioural stratification biomarker and aid in the development of targeted interventions for a subgroup of autistic individuals. En ligne : http://dx.doi.org/10.1186/s13229-022-00520-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=491 Maternal vitamin D during pregnancy and offspring autism and autism-associated traits: a prospective cohort study / Paul MADLEY-DOWD in Molecular Autism, 13 (2022)
![]()
[article]
Titre : Maternal vitamin D during pregnancy and offspring autism and autism-associated traits: a prospective cohort study Type de document : Texte imprimé et/ou numérique Auteurs : Paul MADLEY-DOWD, Auteur ; Christina DARDANI, Auteur ; Robyn E. WOOTTON, Auteur ; Kyle DACK, Auteur ; Tom PALMER, Auteur ; Rupert THURSTON, Auteur ; Alexandra HAVDAHL, Auteur ; Jean GOLDING, Auteur ; Deborah LAWLOR, Auteur ; Dheeraj RAI, Auteur Article en page(s) : 44 p. Langues : Anglais (eng) Mots-clés : Child Pregnancy Female Humans Autistic Disorder/epidemiology/etiology Longitudinal Studies Cohort Studies Prospective Studies Vitamin D Alspac Autism Mendelian randomization Index. décimale : PER Périodiques Résumé : BACKGROUND: There has been a growing interest in the association between maternal levels of vitamin D during pregnancy and offspring autism. However, whether any associations reflect causal effects is still inconclusive. METHODS: We used data from a UK-based pregnancy cohort study (Avon Longitudinal Study of Parents and Children) comprising 7689 births between 1991 and 1992 with maternal blood vitamin D levels recorded during pregnancy and at least one recorded outcome measure, including autism diagnosis and autism-associated traits. The association between each outcome with seasonal and gestational age-adjusted maternal serum 25-hydroxyvitamin D during pregnancy was estimated using confounder-adjusted regression models. Multiple imputation was used to account for missing data, and restricted cubic splines were used to investigate nonlinear associations. Mendelian randomization was used to strengthen causal inference. RESULTS: No strong evidence of an association between maternal serum 25-hydroxyvitamin D during pregnancy and any offspring autism-associated outcome was found using multivariable regression analysis (autism diagnosis: adjusted OR=0.98, 95% CI=0.90-1.06), including with multiple imputation (autism diagnosis: adjusted OR=0.99, 95% CI=0.93-1.06), and no evidence of a causal effect was suggested by Mendelian randomization (autism diagnosis: causal OR=1.08, 95% CI=0.46-2.55). Some evidence of increased odds of autism-associated traits at lower levels of maternal serum 25-hydroxyvitamin D was found using spline analysis. LIMITATIONS: Our study was potentially limited by low power, particularly for diagnosed autism cases as an outcome. The cohort may not have captured the extreme lows of the distribution of serum 25-hydroxyvitamin D, and our analyses may have been biased by residual confounding and missing data. CONCLUSIONS: The present study found no strong evidence of a causal link between maternal vitamin D levels in pregnancy and offspring diagnosis or traits of autism. En ligne : http://dx.doi.org/10.1186/s13229-022-00523-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=491
in Molecular Autism > 13 (2022) . - 44 p.[article] Maternal vitamin D during pregnancy and offspring autism and autism-associated traits: a prospective cohort study [Texte imprimé et/ou numérique] / Paul MADLEY-DOWD, Auteur ; Christina DARDANI, Auteur ; Robyn E. WOOTTON, Auteur ; Kyle DACK, Auteur ; Tom PALMER, Auteur ; Rupert THURSTON, Auteur ; Alexandra HAVDAHL, Auteur ; Jean GOLDING, Auteur ; Deborah LAWLOR, Auteur ; Dheeraj RAI, Auteur . - 44 p.
Langues : Anglais (eng)
in Molecular Autism > 13 (2022) . - 44 p.
Mots-clés : Child Pregnancy Female Humans Autistic Disorder/epidemiology/etiology Longitudinal Studies Cohort Studies Prospective Studies Vitamin D Alspac Autism Mendelian randomization Index. décimale : PER Périodiques Résumé : BACKGROUND: There has been a growing interest in the association between maternal levels of vitamin D during pregnancy and offspring autism. However, whether any associations reflect causal effects is still inconclusive. METHODS: We used data from a UK-based pregnancy cohort study (Avon Longitudinal Study of Parents and Children) comprising 7689 births between 1991 and 1992 with maternal blood vitamin D levels recorded during pregnancy and at least one recorded outcome measure, including autism diagnosis and autism-associated traits. The association between each outcome with seasonal and gestational age-adjusted maternal serum 25-hydroxyvitamin D during pregnancy was estimated using confounder-adjusted regression models. Multiple imputation was used to account for missing data, and restricted cubic splines were used to investigate nonlinear associations. Mendelian randomization was used to strengthen causal inference. RESULTS: No strong evidence of an association between maternal serum 25-hydroxyvitamin D during pregnancy and any offspring autism-associated outcome was found using multivariable regression analysis (autism diagnosis: adjusted OR=0.98, 95% CI=0.90-1.06), including with multiple imputation (autism diagnosis: adjusted OR=0.99, 95% CI=0.93-1.06), and no evidence of a causal effect was suggested by Mendelian randomization (autism diagnosis: causal OR=1.08, 95% CI=0.46-2.55). Some evidence of increased odds of autism-associated traits at lower levels of maternal serum 25-hydroxyvitamin D was found using spline analysis. LIMITATIONS: Our study was potentially limited by low power, particularly for diagnosed autism cases as an outcome. The cohort may not have captured the extreme lows of the distribution of serum 25-hydroxyvitamin D, and our analyses may have been biased by residual confounding and missing data. CONCLUSIONS: The present study found no strong evidence of a causal link between maternal vitamin D levels in pregnancy and offspring diagnosis or traits of autism. En ligne : http://dx.doi.org/10.1186/s13229-022-00523-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=491 Non-suicidal self-injury and its relation to suicide through acquired capability: investigating this causal mechanism in a mainly late-diagnosed autistic sample / Rachel L. MOSELEY in Molecular Autism, 13 (2022)
![]()
[article]
Titre : Non-suicidal self-injury and its relation to suicide through acquired capability: investigating this causal mechanism in a mainly late-diagnosed autistic sample Type de document : Texte imprimé et/ou numérique Auteurs : Rachel L. MOSELEY, Auteur ; Nicola J. GREGORY, Auteur ; Paula SMITH, Auteur ; Carrie ALLISON, Auteur ; Sarah CASSIDY, Auteur ; Simon BARON-COHEN, Auteur Article en page(s) : 45 p. Langues : Anglais (eng) Mots-clés : Adult Humans Female Suicidal Ideation Cross-Sectional Studies Risk Factors Self-Injurious Behavior/epidemiology Pain Acquired capability Nssi Suicide have no competing interests. Professor Baron-Cohen declares a competing interest as per his role as Editor-in-Chief at Molecular Autism. Index. décimale : PER Périodiques Résumé : BACKGROUND: Non-suicidal self-injury (NSSI) has been linked with a higher risk of suicide attempts in autistic and non-autistic people. In the general population, NSSI may confer acquired capability for suicide by eroding one's fear and avoidance of pain and death. The present study aimed to explore acquired capability as the mediator of increased suicide risk conferred by NSSI in autistic and non-autistic adults. METHODS: Autistic and non-autistic adults (n=314, n=312) completed an online survey exploring lifetime suicide attempts, experience with NSSI, and acquired capability for suicide. We explored relationships between lifetime incidence of NSSI and lifetime suicide attempts via three facets of acquired capability (pain tolerance, reduced fear of death, and mental rehearsal of suicide). In self-harming participants (224 autistic and 156 non-autistic), we explored whether particular types and features of NSSI might be especially associated with capability and through that with suicide: namely engagement in scratching, cutting, and self-hitting, and engaging in more numerous forms of NSSI. RESULTS: While a higher frequency of NSSI was associated with all three facets of acquired capability, only reduced fear of death and mental rehearsal of suicide mediated an indirect relationship with lifetime suicide attempts. NSSI also directly predicted more numerous suicide attempts. Autistic people tended towards reduced fear of death and mental rehearsal regardless of NSSI status. Among self-harming autistic and non-autistic participants, cutting and an increased number of NSSI behaviours were associated with lifetime suicide attempts directly and indirectly via acquired capability. In both groups, self-hitting was associated with lifetime suicide attempts only via acquired capability. LIMITATIONS: Our cross-sectional methodology negates inferences of directionality. While we controlled for age, our samples were poorly matched, with the autistic group two times older on average. The autistic sample, predominantly late-diagnosed, female and highly qualified, were unrepresentative of the whole autistic community. CONCLUSIONS: Our data suggest that acquired capability, as measured herein, is an incomplete explanation for the association between NSSI and suicide risk. A broader construct with stable and transient facets may offer greater explanatory power, but it is probable that other variables explain or provide additional means through which this association arises. En ligne : http://dx.doi.org/10.1186/s13229-022-00522-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=491
in Molecular Autism > 13 (2022) . - 45 p.[article] Non-suicidal self-injury and its relation to suicide through acquired capability: investigating this causal mechanism in a mainly late-diagnosed autistic sample [Texte imprimé et/ou numérique] / Rachel L. MOSELEY, Auteur ; Nicola J. GREGORY, Auteur ; Paula SMITH, Auteur ; Carrie ALLISON, Auteur ; Sarah CASSIDY, Auteur ; Simon BARON-COHEN, Auteur . - 45 p.
Langues : Anglais (eng)
in Molecular Autism > 13 (2022) . - 45 p.
Mots-clés : Adult Humans Female Suicidal Ideation Cross-Sectional Studies Risk Factors Self-Injurious Behavior/epidemiology Pain Acquired capability Nssi Suicide have no competing interests. Professor Baron-Cohen declares a competing interest as per his role as Editor-in-Chief at Molecular Autism. Index. décimale : PER Périodiques Résumé : BACKGROUND: Non-suicidal self-injury (NSSI) has been linked with a higher risk of suicide attempts in autistic and non-autistic people. In the general population, NSSI may confer acquired capability for suicide by eroding one's fear and avoidance of pain and death. The present study aimed to explore acquired capability as the mediator of increased suicide risk conferred by NSSI in autistic and non-autistic adults. METHODS: Autistic and non-autistic adults (n=314, n=312) completed an online survey exploring lifetime suicide attempts, experience with NSSI, and acquired capability for suicide. We explored relationships between lifetime incidence of NSSI and lifetime suicide attempts via three facets of acquired capability (pain tolerance, reduced fear of death, and mental rehearsal of suicide). In self-harming participants (224 autistic and 156 non-autistic), we explored whether particular types and features of NSSI might be especially associated with capability and through that with suicide: namely engagement in scratching, cutting, and self-hitting, and engaging in more numerous forms of NSSI. RESULTS: While a higher frequency of NSSI was associated with all three facets of acquired capability, only reduced fear of death and mental rehearsal of suicide mediated an indirect relationship with lifetime suicide attempts. NSSI also directly predicted more numerous suicide attempts. Autistic people tended towards reduced fear of death and mental rehearsal regardless of NSSI status. Among self-harming autistic and non-autistic participants, cutting and an increased number of NSSI behaviours were associated with lifetime suicide attempts directly and indirectly via acquired capability. In both groups, self-hitting was associated with lifetime suicide attempts only via acquired capability. LIMITATIONS: Our cross-sectional methodology negates inferences of directionality. While we controlled for age, our samples were poorly matched, with the autistic group two times older on average. The autistic sample, predominantly late-diagnosed, female and highly qualified, were unrepresentative of the whole autistic community. CONCLUSIONS: Our data suggest that acquired capability, as measured herein, is an incomplete explanation for the association between NSSI and suicide risk. A broader construct with stable and transient facets may offer greater explanatory power, but it is probable that other variables explain or provide additional means through which this association arises. En ligne : http://dx.doi.org/10.1186/s13229-022-00522-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=491 Infant excitation/inhibition balance interacts with executive attention to predict autistic traits in childhood / Virginia CARTER LENO in Molecular Autism, 13 (2022)
![]()
[article]
Titre : Infant excitation/inhibition balance interacts with executive attention to predict autistic traits in childhood Type de document : Texte imprimé et/ou numérique Auteurs : Virginia CARTER LENO, Auteur ; Jannath BEGUM-ALI, Auteur ; Amy GOODWIN, Auteur ; Luke MASON, Auteur ; Greg PASCO, Auteur ; Andrew PICKLES, Auteur ; Shruti GARG, Auteur ; Jonathan GREEN, Auteur ; Tony CHARMAN, Auteur ; Mark H. JOHNSON, Auteur ; Emily J. H. JONES, Auteur ; EDEN, Auteur ; STAARS TEAMS, Auteur Article en page(s) : 46 p. Langues : Anglais (eng) Mots-clés : Humans Child, Preschool Infant Aged Adhd Autism E/I balance Executive functioning Infants NF1 has received royalties from Sage Publications and Guilford Publications. The other authors declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism is proposed to be characterised by an atypical balance of cortical excitation and inhibition (E/I). However, most studies have examined E/I alterations in older autistic individuals, meaning that findings could in part reflect homeostatic compensation. To assess the directionality of effects, it is necessary to examine alterations in E/I balance early in the lifespan before symptom emergence. Recent explanatory frameworks have argued that it is also necessary to consider how early risk features interact with later developing modifier factors to predict autism outcomes. METHOD: We indexed E/I balance in early infancy by extracting the aperiodic exponent of the slope of the electroencephalogram (EEG) power spectrum ('1/f'). To validate our index of E/I balance, we tested for differences in the aperiodic exponent in 10-month-old infants with (n=22) and without (n=27) neurofibromatosis type 1 (NF1), a condition thought to be characterised by alterations to cortical inhibition. We then tested for E/I alterations in a larger heterogeneous longitudinal cohort of infants with and without a family history of neurodevelopmental conditions (n=150) who had been followed to early childhood. We tested the relevance of alterations in E/I balance and our proposed modifier, executive attention, by assessing whether associations between 10-month aperiodic slope and 36-month neurodevelopmental traits were moderated by 24-month executive attention. Analyses adjusted for age at EEG assessment, sex and number of EEG trials. RESULTS: Infants with NF1 were characterised by a higher aperiodic exponent, indicative of greater inhibition, supporting our infant measure of E/I. Longitudinal analyses showed a significant interaction between aperiodic slope and executive attention, such that higher aperiodic exponents predicted greater autistic traits in childhood, but only in infants who also had weaker executive functioning abilities. LIMITATIONS: The current study relied on parent report of infant executive functioning-type abilities; future work is required to replicate effects with objective measures of cognition. CONCLUSIONS: Results suggest alterations in E/I balance are on the developmental pathway to autism outcomes, and that higher executive functioning abilities may buffer the impact of early cortical atypicalities, consistent with proposals that stronger executive functioning abilities may modify the impact of a wide range of risk factors. En ligne : http://dx.doi.org/10.1186/s13229-022-00526-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=491
in Molecular Autism > 13 (2022) . - 46 p.[article] Infant excitation/inhibition balance interacts with executive attention to predict autistic traits in childhood [Texte imprimé et/ou numérique] / Virginia CARTER LENO, Auteur ; Jannath BEGUM-ALI, Auteur ; Amy GOODWIN, Auteur ; Luke MASON, Auteur ; Greg PASCO, Auteur ; Andrew PICKLES, Auteur ; Shruti GARG, Auteur ; Jonathan GREEN, Auteur ; Tony CHARMAN, Auteur ; Mark H. JOHNSON, Auteur ; Emily J. H. JONES, Auteur ; EDEN, Auteur ; STAARS TEAMS, Auteur . - 46 p.
Langues : Anglais (eng)
in Molecular Autism > 13 (2022) . - 46 p.
Mots-clés : Humans Child, Preschool Infant Aged Adhd Autism E/I balance Executive functioning Infants NF1 has received royalties from Sage Publications and Guilford Publications. The other authors declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism is proposed to be characterised by an atypical balance of cortical excitation and inhibition (E/I). However, most studies have examined E/I alterations in older autistic individuals, meaning that findings could in part reflect homeostatic compensation. To assess the directionality of effects, it is necessary to examine alterations in E/I balance early in the lifespan before symptom emergence. Recent explanatory frameworks have argued that it is also necessary to consider how early risk features interact with later developing modifier factors to predict autism outcomes. METHOD: We indexed E/I balance in early infancy by extracting the aperiodic exponent of the slope of the electroencephalogram (EEG) power spectrum ('1/f'). To validate our index of E/I balance, we tested for differences in the aperiodic exponent in 10-month-old infants with (n=22) and without (n=27) neurofibromatosis type 1 (NF1), a condition thought to be characterised by alterations to cortical inhibition. We then tested for E/I alterations in a larger heterogeneous longitudinal cohort of infants with and without a family history of neurodevelopmental conditions (n=150) who had been followed to early childhood. We tested the relevance of alterations in E/I balance and our proposed modifier, executive attention, by assessing whether associations between 10-month aperiodic slope and 36-month neurodevelopmental traits were moderated by 24-month executive attention. Analyses adjusted for age at EEG assessment, sex and number of EEG trials. RESULTS: Infants with NF1 were characterised by a higher aperiodic exponent, indicative of greater inhibition, supporting our infant measure of E/I. Longitudinal analyses showed a significant interaction between aperiodic slope and executive attention, such that higher aperiodic exponents predicted greater autistic traits in childhood, but only in infants who also had weaker executive functioning abilities. LIMITATIONS: The current study relied on parent report of infant executive functioning-type abilities; future work is required to replicate effects with objective measures of cognition. CONCLUSIONS: Results suggest alterations in E/I balance are on the developmental pathway to autism outcomes, and that higher executive functioning abilities may buffer the impact of early cortical atypicalities, consistent with proposals that stronger executive functioning abilities may modify the impact of a wide range of risk factors. En ligne : http://dx.doi.org/10.1186/s13229-022-00526-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=491 Altered frontal connectivity as a mechanism for executive function deficits in fragile X syndrome / Lauren M. SCHMITT in Molecular Autism, 13 (2022)
![]()
[article]
Titre : Altered frontal connectivity as a mechanism for executive function deficits in fragile X syndrome Type de document : Texte imprimé et/ou numérique Auteurs : Lauren M. SCHMITT, Auteur ; Joy LI, Auteur ; Rui LIU, Auteur ; Paul S. HORN, Auteur ; John A. SWEENEY, Auteur ; Craig A. ERICKSON, Auteur ; Ernest V. PEDAPATI, Auteur Article en page(s) : 47 p. Langues : Anglais (eng) Mots-clés : Child Male Humans Female Fragile X Syndrome Executive Function Autism Spectrum Disorder Electroencephalography/methods Brain Connectivity Eeg Electroencephalography Fxs Fragile X syndrome commercial or financial relationships that could be construed as a potential conflict of interest for the current manuscript. Index. décimale : PER Périodiques Résumé : BACKGROUND: Fragile X syndrome (FXS) is the leading inherited monogenic cause of intellectual disability and autism spectrum disorder. Executive function (EF), necessary for adaptive goal-oriented behavior and dependent on frontal lobe function, is impaired in individuals with FXS. Yet, little is known how alterations in frontal lobe neural activity is related to EF deficits in FXS. METHODS: Sixty-one participants with FXS (54% males) and 71 age- and sex-matched typically-developing controls (TDC; 58% males) completed a five-minute resting state electroencephalography (EEG) protocol and a computerized battery of tests of EF, the Test of Attentional Performance for Children (KiTAP). Following source localization (minimum-norm estimate), we computed debiased weighted phase lag index (dWPLI), a phase connectivity value, for pairings between 18 nodes in frontal regions for gamma (30-55Â Hz) and alpha (10.5-12.5Â Hz) bands. Linear models were generated with fixed factors of group, sex, frequency, and connection. Relationships between frontal connectivity and EF variables also were examined. RESULTS: Individuals with FXS demonstrated increased gamma band and reduced alpha band connectivity across all frontal regions and across hemispheres compared to TDC. After controlling for nonverbal IQ, increased error rates on EF tasks were associated with increased gamma band and reduced alpha band connectivity. LIMITATIONS: Frontal connectivity findings are limited to intrinsic brain activity during rest and may not generalize to frontal connectivity during EF tasks or everyday function. CONCLUSIONS: We report gamma hyper-connectivity and alpha hypo-connectivity within source-localized frontal brain regions in FXS compared to TDC during resting-state EEG. For the first time in FXS, we report significant associations between EF and altered frontal connectivity, with increased error rate relating to increased gamma band connectivity and reduced alpha band connectivity. These findings suggest increased phase connectivity within gamma band may impair EF performance, whereas greater alpha band connectivity may provide compensatory support for EF. Together, these findings provide important insight into neurophysiological mechanisms of EF deficits in FXS and provide novel targets for treatment development. En ligne : http://dx.doi.org/10.1186/s13229-022-00527-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=491
in Molecular Autism > 13 (2022) . - 47 p.[article] Altered frontal connectivity as a mechanism for executive function deficits in fragile X syndrome [Texte imprimé et/ou numérique] / Lauren M. SCHMITT, Auteur ; Joy LI, Auteur ; Rui LIU, Auteur ; Paul S. HORN, Auteur ; John A. SWEENEY, Auteur ; Craig A. ERICKSON, Auteur ; Ernest V. PEDAPATI, Auteur . - 47 p.
Langues : Anglais (eng)
in Molecular Autism > 13 (2022) . - 47 p.
Mots-clés : Child Male Humans Female Fragile X Syndrome Executive Function Autism Spectrum Disorder Electroencephalography/methods Brain Connectivity Eeg Electroencephalography Fxs Fragile X syndrome commercial or financial relationships that could be construed as a potential conflict of interest for the current manuscript. Index. décimale : PER Périodiques Résumé : BACKGROUND: Fragile X syndrome (FXS) is the leading inherited monogenic cause of intellectual disability and autism spectrum disorder. Executive function (EF), necessary for adaptive goal-oriented behavior and dependent on frontal lobe function, is impaired in individuals with FXS. Yet, little is known how alterations in frontal lobe neural activity is related to EF deficits in FXS. METHODS: Sixty-one participants with FXS (54% males) and 71 age- and sex-matched typically-developing controls (TDC; 58% males) completed a five-minute resting state electroencephalography (EEG) protocol and a computerized battery of tests of EF, the Test of Attentional Performance for Children (KiTAP). Following source localization (minimum-norm estimate), we computed debiased weighted phase lag index (dWPLI), a phase connectivity value, for pairings between 18 nodes in frontal regions for gamma (30-55Â Hz) and alpha (10.5-12.5Â Hz) bands. Linear models were generated with fixed factors of group, sex, frequency, and connection. Relationships between frontal connectivity and EF variables also were examined. RESULTS: Individuals with FXS demonstrated increased gamma band and reduced alpha band connectivity across all frontal regions and across hemispheres compared to TDC. After controlling for nonverbal IQ, increased error rates on EF tasks were associated with increased gamma band and reduced alpha band connectivity. LIMITATIONS: Frontal connectivity findings are limited to intrinsic brain activity during rest and may not generalize to frontal connectivity during EF tasks or everyday function. CONCLUSIONS: We report gamma hyper-connectivity and alpha hypo-connectivity within source-localized frontal brain regions in FXS compared to TDC during resting-state EEG. For the first time in FXS, we report significant associations between EF and altered frontal connectivity, with increased error rate relating to increased gamma band connectivity and reduced alpha band connectivity. These findings suggest increased phase connectivity within gamma band may impair EF performance, whereas greater alpha band connectivity may provide compensatory support for EF. Together, these findings provide important insight into neurophysiological mechanisms of EF deficits in FXS and provide novel targets for treatment development. En ligne : http://dx.doi.org/10.1186/s13229-022-00527-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=491 Experience-dependent changes in hippocampal spatial activity and hippocampal circuit function are disrupted in a rat model of Fragile X Syndrome / Antonis ASIMINAS in Molecular Autism, 13 (2022)
![]()
[article]
Titre : Experience-dependent changes in hippocampal spatial activity and hippocampal circuit function are disrupted in a rat model of Fragile X Syndrome Type de document : Texte imprimé et/ou numérique Auteurs : Antonis ASIMINAS, Auteur ; Sam A. BOOKER, Auteur ; Owen R. DANDO, Auteur ; Zrinko KOZIC, Auteur ; Daisy ARKELL, Auteur ; Felicity H. INKPEN, Auteur ; Anna SUMERA, Auteur ; Irem AKYEL, Auteur ; Peter C. KIND, Auteur ; Emma R. WOOD, Auteur Article en page(s) : 49 p. Langues : Anglais (eng) Mots-clés : Mice Rats Animals Fragile X Syndrome/genetics Intellectual Disability Autism Spectrum Disorder Mice, Knockout Hippocampus/metabolism Fragile X Mental Retardation Protein/genetics Disease Models, Animal Index. décimale : PER Périodiques Résumé : BACKGROUND: Fragile X syndrome (FXS) is a common single gene cause of intellectual disability and autism spectrum disorder. Cognitive inflexibility is one of the hallmarks of FXS with affected individuals showing extreme difficulty adapting to novel or complex situations. To explore the neural correlates of this cognitive inflexibility, we used a rat model of FXS (Fmr1(-/y)). METHODS: We recorded from the CA1 in Fmr1(-/y) and WT littermates over six 10-min exploration sessions in a novel environment-three sessions per day (ITI 10Â min). Our recordings yielded 288 and 246 putative pyramidal cells from 7 WT and 7 Fmr1(-/y) rats, respectively. RESULTS: On the first day of exploration of a novel environment, the firing rate and spatial tuning of CA1 pyramidal neurons was similar between wild-type (WT) and Fmr1(-/y) rats. However, while CA1 pyramidal neurons from WT rats showed experience-dependent changes in firing and spatial tuning between the first and second day of exposure to the environment, these changes were decreased or absent in CA1 neurons of Fmr1(-/y) rats. These findings were consistent with increased excitability of Fmr1(-/y) CA1 neurons in ex vivo hippocampal slices, which correlated with reduced synaptic inputs from the medial entorhinal cortex. Lastly, activity patterns of CA1 pyramidal neurons were dis-coordinated with respect to hippocampal oscillatory activity in Fmr1(-/y) rats. LIMITATIONS: It is still unclear how the observed circuit function abnormalities give rise to behavioural deficits in Fmr1(-/y) rats. Future experiments will focus on this connection as well as the contribution of other neuronal cell types in the hippocampal circuit pathophysiology associated with the loss of FMRP. It would also be interesting to see if hippocampal circuit deficits converge with those seen in other rodent models of intellectual disability. CONCLUSIONS: In conclusion, we found that hippocampal place cells from Fmr1(-/y) rats show similar spatial firing properties as those from WT rats but do not show the same experience-dependent increase in spatial specificity or the experience-dependent changes in network coordination. Our findings offer support to a network-level origin of cognitive deficits in FXS. En ligne : http://dx.doi.org/10.1186/s13229-022-00528-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=491
in Molecular Autism > 13 (2022) . - 49 p.[article] Experience-dependent changes in hippocampal spatial activity and hippocampal circuit function are disrupted in a rat model of Fragile X Syndrome [Texte imprimé et/ou numérique] / Antonis ASIMINAS, Auteur ; Sam A. BOOKER, Auteur ; Owen R. DANDO, Auteur ; Zrinko KOZIC, Auteur ; Daisy ARKELL, Auteur ; Felicity H. INKPEN, Auteur ; Anna SUMERA, Auteur ; Irem AKYEL, Auteur ; Peter C. KIND, Auteur ; Emma R. WOOD, Auteur . - 49 p.
Langues : Anglais (eng)
in Molecular Autism > 13 (2022) . - 49 p.
Mots-clés : Mice Rats Animals Fragile X Syndrome/genetics Intellectual Disability Autism Spectrum Disorder Mice, Knockout Hippocampus/metabolism Fragile X Mental Retardation Protein/genetics Disease Models, Animal Index. décimale : PER Périodiques Résumé : BACKGROUND: Fragile X syndrome (FXS) is a common single gene cause of intellectual disability and autism spectrum disorder. Cognitive inflexibility is one of the hallmarks of FXS with affected individuals showing extreme difficulty adapting to novel or complex situations. To explore the neural correlates of this cognitive inflexibility, we used a rat model of FXS (Fmr1(-/y)). METHODS: We recorded from the CA1 in Fmr1(-/y) and WT littermates over six 10-min exploration sessions in a novel environment-three sessions per day (ITI 10Â min). Our recordings yielded 288 and 246 putative pyramidal cells from 7 WT and 7 Fmr1(-/y) rats, respectively. RESULTS: On the first day of exploration of a novel environment, the firing rate and spatial tuning of CA1 pyramidal neurons was similar between wild-type (WT) and Fmr1(-/y) rats. However, while CA1 pyramidal neurons from WT rats showed experience-dependent changes in firing and spatial tuning between the first and second day of exposure to the environment, these changes were decreased or absent in CA1 neurons of Fmr1(-/y) rats. These findings were consistent with increased excitability of Fmr1(-/y) CA1 neurons in ex vivo hippocampal slices, which correlated with reduced synaptic inputs from the medial entorhinal cortex. Lastly, activity patterns of CA1 pyramidal neurons were dis-coordinated with respect to hippocampal oscillatory activity in Fmr1(-/y) rats. LIMITATIONS: It is still unclear how the observed circuit function abnormalities give rise to behavioural deficits in Fmr1(-/y) rats. Future experiments will focus on this connection as well as the contribution of other neuronal cell types in the hippocampal circuit pathophysiology associated with the loss of FMRP. It would also be interesting to see if hippocampal circuit deficits converge with those seen in other rodent models of intellectual disability. CONCLUSIONS: In conclusion, we found that hippocampal place cells from Fmr1(-/y) rats show similar spatial firing properties as those from WT rats but do not show the same experience-dependent increase in spatial specificity or the experience-dependent changes in network coordination. Our findings offer support to a network-level origin of cognitive deficits in FXS. En ligne : http://dx.doi.org/10.1186/s13229-022-00528-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=491 Brainstem white matter microstructure is associated with hyporesponsiveness and overall sensory features in autistic children / Olivia SURGENT in Molecular Autism, 13 (2022)
![]()
[article]
Titre : Brainstem white matter microstructure is associated with hyporesponsiveness and overall sensory features in autistic children Type de document : Texte imprimé et/ou numérique Auteurs : Olivia SURGENT, Auteur ; Ali RIAZ, Auteur ; Karla K. AUSDERAU, Auteur ; Nagesh ADLURU, Auteur ; Gregory R. KIRK, Auteur ; Jose GUERRERO-GONZALEZ, Auteur ; Emily C. SKALETSKI, Auteur ; Steven R. KECSKEMETI, Auteur ; Douglas C. DEAN III, Auteur ; Susan ELLIS WEISMER, Auteur ; Andrew L. ALEXANDER, Auteur ; Brittany G. TRAVERS, Auteur Article en page(s) : 48 p. Langues : Anglais (eng) Mots-clés : Humans Child White Matter Brain Quality of Life Autistic Disorder Brain Stem Autism Brainstem Dti Sensory features Voxel-based analysis White matter TherVoyant). While both companies are involved in developing MRI-based surgery techniques, neither are associated with any current areas of his research, including the present publication. All other authors report no biomedical financial interests of potential conflicts of interest. Index. décimale : PER Périodiques Résumé : BACKGROUND: Elevated or reduced responses to sensory stimuli, known as sensory features, are common in autistic individuals and often impact quality of life. Little is known about the neurobiological basis of sensory features in autistic children. However, the brainstem may offer critical insights as it has been associated with both basic sensory processing and core features of autism. METHODS: Diffusion-weighted imaging (DWI) and parent-report of sensory features were acquired from 133 children (61 autistic children with and 72 non-autistic children, 6-11Â years-old). Leveraging novel DWI processing techniques, we investigated the relationship between sensory features and white matter microstructure properties (free-water-elimination-corrected fractional anisotropy [FA] and mean diffusivity [MD]) in precisely delineated brainstem white matter tracts. Follow-up analyses assessed relationships between microstructure and sensory response patterns/modalities and analyzed whole brain white matter using voxel-based analysis. RESULTS: Results revealed distinct relationships between brainstem microstructure and sensory features in autistic children compared to non-autistic children. In autistic children, more prominent sensory features were generally associated with lower MD. Further, in autistic children, sensory hyporesponsiveness and tactile responsivity were strongly associated with white matter microstructure in nearly all brainstem tracts. Follow-up voxel-based analyses confirmed that these relationships were more prominent in the brainstem/cerebellum, with additional sensory-brain findings in the autistic group in the white matter of the primary motor and somatosensory cortices, the occipital lobe, the inferior parietal lobe, and the thalamic projections. LIMITATIONS: All participants communicated via spoken language and acclimated to the sensory environment of an MRI session, which should be considered when assessing the generalizability of this work to the whole of the autism spectrum. CONCLUSIONS: These findings suggest unique brainstem white matter contributions to sensory features in autistic children compared to non-autistic children. The brainstem correlates of sensory features underscore the potential reflex-like nature of behavioral responses to sensory stimuli in autism and have implications for how we conceptualize and address sensory features in autistic populations. En ligne : http://dx.doi.org/10.1186/s13229-022-00524-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=491
in Molecular Autism > 13 (2022) . - 48 p.[article] Brainstem white matter microstructure is associated with hyporesponsiveness and overall sensory features in autistic children [Texte imprimé et/ou numérique] / Olivia SURGENT, Auteur ; Ali RIAZ, Auteur ; Karla K. AUSDERAU, Auteur ; Nagesh ADLURU, Auteur ; Gregory R. KIRK, Auteur ; Jose GUERRERO-GONZALEZ, Auteur ; Emily C. SKALETSKI, Auteur ; Steven R. KECSKEMETI, Auteur ; Douglas C. DEAN III, Auteur ; Susan ELLIS WEISMER, Auteur ; Andrew L. ALEXANDER, Auteur ; Brittany G. TRAVERS, Auteur . - 48 p.
Langues : Anglais (eng)
in Molecular Autism > 13 (2022) . - 48 p.
Mots-clés : Humans Child White Matter Brain Quality of Life Autistic Disorder Brain Stem Autism Brainstem Dti Sensory features Voxel-based analysis White matter TherVoyant). While both companies are involved in developing MRI-based surgery techniques, neither are associated with any current areas of his research, including the present publication. All other authors report no biomedical financial interests of potential conflicts of interest. Index. décimale : PER Périodiques Résumé : BACKGROUND: Elevated or reduced responses to sensory stimuli, known as sensory features, are common in autistic individuals and often impact quality of life. Little is known about the neurobiological basis of sensory features in autistic children. However, the brainstem may offer critical insights as it has been associated with both basic sensory processing and core features of autism. METHODS: Diffusion-weighted imaging (DWI) and parent-report of sensory features were acquired from 133 children (61 autistic children with and 72 non-autistic children, 6-11Â years-old). Leveraging novel DWI processing techniques, we investigated the relationship between sensory features and white matter microstructure properties (free-water-elimination-corrected fractional anisotropy [FA] and mean diffusivity [MD]) in precisely delineated brainstem white matter tracts. Follow-up analyses assessed relationships between microstructure and sensory response patterns/modalities and analyzed whole brain white matter using voxel-based analysis. RESULTS: Results revealed distinct relationships between brainstem microstructure and sensory features in autistic children compared to non-autistic children. In autistic children, more prominent sensory features were generally associated with lower MD. Further, in autistic children, sensory hyporesponsiveness and tactile responsivity were strongly associated with white matter microstructure in nearly all brainstem tracts. Follow-up voxel-based analyses confirmed that these relationships were more prominent in the brainstem/cerebellum, with additional sensory-brain findings in the autistic group in the white matter of the primary motor and somatosensory cortices, the occipital lobe, the inferior parietal lobe, and the thalamic projections. LIMITATIONS: All participants communicated via spoken language and acclimated to the sensory environment of an MRI session, which should be considered when assessing the generalizability of this work to the whole of the autism spectrum. CONCLUSIONS: These findings suggest unique brainstem white matter contributions to sensory features in autistic children compared to non-autistic children. The brainstem correlates of sensory features underscore the potential reflex-like nature of behavioral responses to sensory stimuli in autism and have implications for how we conceptualize and address sensory features in autistic populations. En ligne : http://dx.doi.org/10.1186/s13229-022-00524-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=491 Personal victimization experiences of autistic and non-autistic children / Natalie LIBSTER in Molecular Autism, 13 (2022)
![]()
[article]
Titre : Personal victimization experiences of autistic and non-autistic children Type de document : Texte imprimé et/ou numérique Auteurs : Natalie LIBSTER, Auteur ; Azia KNOX, Auteur ; Selin ENGIN, Auteur ; Daniel GESCHWIND, Auteur ; Julia PARISH-MORRIS, Auteur ; Connie KASARI, Auteur Article en page(s) : 51 p. Langues : Anglais (eng) Mots-clés : Humans Male Child Female Autistic Disorder Crime Victims Bullying Peer Group Cognition Autism spectrum disorder Autism symptom severity Bullying victimization Sex differences Social affect Index. décimale : PER Périodiques Résumé : BACKGROUND: Autistic children report higher levels of bullying victimization than their non-autistic peers. However, autistic children with fewer social difficulties, as measured on the Autism Diagnostic Observation Schedule (ADOS), are more likely to report being bullied. Autistic children with stronger social skills may not only be more likely to identify and report incidents of bullying, but they may also be more likely to interact with their non-autistic peers, increasing their likelihood of being victimized. Autistic girls may be especially at-risk of experiencing bullying victimization, as a growing body of research suggests that autistic girls demonstrate fewer social difficulties and are more socially motivated than autistic boys. Here, we explored reported problems with peers and bullying victimization among a carefully matched sample of autistic and non-autistic boys and girls. Qualitative methods were further implemented to gain a more holistic understanding of the social experiences of autistic boys and girls. METHODS: This mixed-methods study analyzed the transcribed clinical evaluations of 58 autistic children (29 girls) matched to 42 non-autistic children (21 girls) on age and IQ. Within each diagnostic group, boys and girls were matched on ADOS severity score. We compared reported problems with peers and bullying victimization across sex and diagnosis. Among autistic children, we further examined whether ADOS social affect (SA), restricted repetitive behaviors, and severity scores predicted problems with peers and bullying victimization. We then identified themes related to personal experiences of victimization. RESULTS: Autistic children were more likely than non-autistic children to have experienced bullying victimization, and autistic children with lower ADOS severity and SA scores were more likely to report having been bullied. While autistic boys and girls reported similar levels of bullying victimization, qualitative analyses revealed sex differences in the underlying causes of peer conflict. LIMITATIONS: This study was a secondary data analysis. The standardized set of questions on the ADOS limited the amount of information that children provided about their peer relationships, and variations in follow-up questions may have influenced children's responses. CONCLUSIONS: Although autism symptomatology places autistic children at greater risk for bullying victimization compared to their non-autistic peers, greater social challenges among autistic children are associated with lower rates of victimization. This study further highlights the importance of using mixed-methods approaches to discover nuances in the social experiences of autistic girls and boys that may become opportunities for support. En ligne : http://dx.doi.org/10.1186/s13229-022-00531-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=491
in Molecular Autism > 13 (2022) . - 51 p.[article] Personal victimization experiences of autistic and non-autistic children [Texte imprimé et/ou numérique] / Natalie LIBSTER, Auteur ; Azia KNOX, Auteur ; Selin ENGIN, Auteur ; Daniel GESCHWIND, Auteur ; Julia PARISH-MORRIS, Auteur ; Connie KASARI, Auteur . - 51 p.
Langues : Anglais (eng)
in Molecular Autism > 13 (2022) . - 51 p.
Mots-clés : Humans Male Child Female Autistic Disorder Crime Victims Bullying Peer Group Cognition Autism spectrum disorder Autism symptom severity Bullying victimization Sex differences Social affect Index. décimale : PER Périodiques Résumé : BACKGROUND: Autistic children report higher levels of bullying victimization than their non-autistic peers. However, autistic children with fewer social difficulties, as measured on the Autism Diagnostic Observation Schedule (ADOS), are more likely to report being bullied. Autistic children with stronger social skills may not only be more likely to identify and report incidents of bullying, but they may also be more likely to interact with their non-autistic peers, increasing their likelihood of being victimized. Autistic girls may be especially at-risk of experiencing bullying victimization, as a growing body of research suggests that autistic girls demonstrate fewer social difficulties and are more socially motivated than autistic boys. Here, we explored reported problems with peers and bullying victimization among a carefully matched sample of autistic and non-autistic boys and girls. Qualitative methods were further implemented to gain a more holistic understanding of the social experiences of autistic boys and girls. METHODS: This mixed-methods study analyzed the transcribed clinical evaluations of 58 autistic children (29 girls) matched to 42 non-autistic children (21 girls) on age and IQ. Within each diagnostic group, boys and girls were matched on ADOS severity score. We compared reported problems with peers and bullying victimization across sex and diagnosis. Among autistic children, we further examined whether ADOS social affect (SA), restricted repetitive behaviors, and severity scores predicted problems with peers and bullying victimization. We then identified themes related to personal experiences of victimization. RESULTS: Autistic children were more likely than non-autistic children to have experienced bullying victimization, and autistic children with lower ADOS severity and SA scores were more likely to report having been bullied. While autistic boys and girls reported similar levels of bullying victimization, qualitative analyses revealed sex differences in the underlying causes of peer conflict. LIMITATIONS: This study was a secondary data analysis. The standardized set of questions on the ADOS limited the amount of information that children provided about their peer relationships, and variations in follow-up questions may have influenced children's responses. CONCLUSIONS: Although autism symptomatology places autistic children at greater risk for bullying victimization compared to their non-autistic peers, greater social challenges among autistic children are associated with lower rates of victimization. This study further highlights the importance of using mixed-methods approaches to discover nuances in the social experiences of autistic girls and boys that may become opportunities for support. En ligne : http://dx.doi.org/10.1186/s13229-022-00531-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=491 Autism spectrum disorder symptom expression in individuals with 3q29 deletion syndrome / Rebecca M. POLLAK in Molecular Autism, 13 (2022)
![]()
[article]
Titre : Autism spectrum disorder symptom expression in individuals with 3q29 deletion syndrome Type de document : Texte imprimé et/ou numérique Auteurs : Rebecca M. POLLAK, Auteur ; Jordan E. PINCUS, Auteur ; T. Lindsey BURRELL, Auteur ; Joseph F. CUBELLS, Auteur ; Cheryl KLAIMAN, Auteur ; Melissa M. MURPHY, Auteur ; Celine A. SAULNIER, Auteur ; Elaine F. WALKER, Auteur ; Stormi PULVER. WHITE, Auteur ; Jennifer G. MULLE, Auteur Article en page(s) : 50 p. Langues : Anglais (eng) Mots-clés : Male Female Humans Autism Spectrum Disorder/diagnosis/genetics Syndrome Social Skills Surveys and Questionnaires Phenotype 3q29 deletion Adi-r Ados-2 Autism Copy number variants Developmental delay Genomic disorder Psychiatric genetics other authors report no conflicts of interest. Index. décimale : PER Périodiques Résumé : BACKGROUND: The 1.6Â Mb 3q29 deletion is associated with neurodevelopmental and neuropsychiatric phenotypes, including a 19-fold increased risk for autism spectrum disorder (ASD). Previous work by our team identified elevated social disability in this population via parent-report questionnaires. However, clinical features of ASD in this population have not been explored in detail. METHODS: Thirty-one individuals with 3q29 deletion syndrome (3q29del, 61.3% male) were evaluated using two gold-standard clinical ASD evaluations: the Autism Diagnostic Observation Schedule, Second Edition (ADOS-2), and the Autism Diagnostic Interview, Revised (ADI-R). Four matched comparators for each subject were ascertained from the National Database for Autism Research. Item-level scores on the ADOS-2 and ADI-R were compared between subjects with 3q29del and matched comparators. RESULTS: Subjects with 3q29del and no ASD (3q29del-ASD) had greater evidence of social disability compared to typically developing (TD) comparison subjects across the ADOS-2. Subjects with 3q29del and ASD (3q29del + ASD) were largely indistinguishable from non-syndromic ASD (nsASD) subjects on the ADOS-2. 3q29del + ASD performed significantly better on social communication on the ADI-R than nsASD (3q29 + ASD mean=11.36; nsASD mean=15.70; p=0.01), and this was driven by reduced deficits in nonverbal communication (3q29 + ASD mean=1.73; nsASD mean=3.63; p=0.03). 3q29del + ASD reported significantly later age at the first two-word phrase compared to nsASD (3q29del + ASD mean=43.89Â months; nsASD mean=37.86Â months; p=0.01). However, speech delay was not related to improved nonverbal communication in 3q29del + ASD. LIMITATIONS: There were not enough TD comparators with ADI-R data in NDAR to include in the present analysis. Additionally, our relatively small sample size made it difficult to assess race and ethnicity effects. CONCLUSIONS: 3q29del is associated with significant social disability, irrespective of ASD diagnosis. 3q29del + ASD have similar levels of social disability to nsASD, while 3q29del-ASD have significantly increased social disability compared to TD individuals. However, social communication is reasonably well preserved in 3q29del + ASD relative to nsASD. It is critical that verbal ability and social disability be examined separately in this population to ensure equal access to ASD and social skills evaluations and services. En ligne : http://dx.doi.org/10.1186/s13229-022-00533-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=491
in Molecular Autism > 13 (2022) . - 50 p.[article] Autism spectrum disorder symptom expression in individuals with 3q29 deletion syndrome [Texte imprimé et/ou numérique] / Rebecca M. POLLAK, Auteur ; Jordan E. PINCUS, Auteur ; T. Lindsey BURRELL, Auteur ; Joseph F. CUBELLS, Auteur ; Cheryl KLAIMAN, Auteur ; Melissa M. MURPHY, Auteur ; Celine A. SAULNIER, Auteur ; Elaine F. WALKER, Auteur ; Stormi PULVER. WHITE, Auteur ; Jennifer G. MULLE, Auteur . - 50 p.
Langues : Anglais (eng)
in Molecular Autism > 13 (2022) . - 50 p.
Mots-clés : Male Female Humans Autism Spectrum Disorder/diagnosis/genetics Syndrome Social Skills Surveys and Questionnaires Phenotype 3q29 deletion Adi-r Ados-2 Autism Copy number variants Developmental delay Genomic disorder Psychiatric genetics other authors report no conflicts of interest. Index. décimale : PER Périodiques Résumé : BACKGROUND: The 1.6Â Mb 3q29 deletion is associated with neurodevelopmental and neuropsychiatric phenotypes, including a 19-fold increased risk for autism spectrum disorder (ASD). Previous work by our team identified elevated social disability in this population via parent-report questionnaires. However, clinical features of ASD in this population have not been explored in detail. METHODS: Thirty-one individuals with 3q29 deletion syndrome (3q29del, 61.3% male) were evaluated using two gold-standard clinical ASD evaluations: the Autism Diagnostic Observation Schedule, Second Edition (ADOS-2), and the Autism Diagnostic Interview, Revised (ADI-R). Four matched comparators for each subject were ascertained from the National Database for Autism Research. Item-level scores on the ADOS-2 and ADI-R were compared between subjects with 3q29del and matched comparators. RESULTS: Subjects with 3q29del and no ASD (3q29del-ASD) had greater evidence of social disability compared to typically developing (TD) comparison subjects across the ADOS-2. Subjects with 3q29del and ASD (3q29del + ASD) were largely indistinguishable from non-syndromic ASD (nsASD) subjects on the ADOS-2. 3q29del + ASD performed significantly better on social communication on the ADI-R than nsASD (3q29 + ASD mean=11.36; nsASD mean=15.70; p=0.01), and this was driven by reduced deficits in nonverbal communication (3q29 + ASD mean=1.73; nsASD mean=3.63; p=0.03). 3q29del + ASD reported significantly later age at the first two-word phrase compared to nsASD (3q29del + ASD mean=43.89Â months; nsASD mean=37.86Â months; p=0.01). However, speech delay was not related to improved nonverbal communication in 3q29del + ASD. LIMITATIONS: There were not enough TD comparators with ADI-R data in NDAR to include in the present analysis. Additionally, our relatively small sample size made it difficult to assess race and ethnicity effects. CONCLUSIONS: 3q29del is associated with significant social disability, irrespective of ASD diagnosis. 3q29del + ASD have similar levels of social disability to nsASD, while 3q29del-ASD have significantly increased social disability compared to TD individuals. However, social communication is reasonably well preserved in 3q29del + ASD relative to nsASD. It is critical that verbal ability and social disability be examined separately in this population to ensure equal access to ASD and social skills evaluations and services. En ligne : http://dx.doi.org/10.1186/s13229-022-00533-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=491 Inter-individual heterogeneity of functional brain networks in children with autism spectrum disorder / Xiaonan GUO in Molecular Autism, 13 (2022)
![]()
[article]
Titre : Inter-individual heterogeneity of functional brain networks in children with autism spectrum disorder Type de document : Texte imprimé et/ou numérique Auteurs : Xiaonan GUO, Auteur ; Guangjin ZHAI, Auteur ; Junfeng LIU, Auteur ; Yabo CAO, Auteur ; Xia ZHANG, Auteur ; Dong CUI, Auteur ; Le GAO, Auteur Article en page(s) : 52 p. Langues : Anglais (eng) Mots-clés : Humans Male Child Autism Spectrum Disorder/diagnostic imaging Brain Mapping/methods Magnetic Resonance Imaging/methods Brain/diagnostic imaging Autistic Disorder Neural Pathways/diagnostic imaging Autism spectrum disorder Functional connectivity Functional magnetic resonance imaging Subtype k-means clustering Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental disorder with considerable clinical heterogeneity. This study aimed to explore the heterogeneity of ASD based on inter-individual heterogeneity of functional brain networks. METHODS: Resting-state functional magnetic resonance imaging data from the Autism Brain Imaging Data Exchange database were used in this study for 105 children with ASD and 102 demographically matched typical controls (TC) children. Functional connectivity (FC) networks were first obtained for ASD and TC groups, and inter-individual deviation of functional connectivity (IDFC) from the TC group was then calculated for each individual with ASD. A k-means clustering algorithm was used to obtain ASD subtypes based on IDFC patterns. The FC patterns were further compared between ASD subtypes and the TC group from the brain region, network, and whole-brain levels. The relationship between IDFC and the severity of clinical symptoms of ASD for ASD subtypes was also analyzed using a support vector regression model. RESULTS: Two ASD subtypes were identified based on the IDFC patterns. Compared with the TC group, the ASD subtype 1 group exhibited a hypoconnectivity pattern and the ASD subtype 2 group exhibited a hyperconnectivity pattern. IDFC for ASD subtype 1 and subtype 2 was found to predict the severity of social communication impairments and the severity of restricted and repetitive behaviors in ASD, respectively. LIMITATIONS: Only male children were selected for this study, which limits the ability to study the effects of gender and development on ASD heterogeneity. CONCLUSIONS: These results suggest the existence of subtypes with different FC patterns in ASD and provide insight into the complex pathophysiological mechanism of clinical manifestations of ASD. En ligne : http://dx.doi.org/10.1186/s13229-022-00535-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=491
in Molecular Autism > 13 (2022) . - 52 p.[article] Inter-individual heterogeneity of functional brain networks in children with autism spectrum disorder [Texte imprimé et/ou numérique] / Xiaonan GUO, Auteur ; Guangjin ZHAI, Auteur ; Junfeng LIU, Auteur ; Yabo CAO, Auteur ; Xia ZHANG, Auteur ; Dong CUI, Auteur ; Le GAO, Auteur . - 52 p.
Langues : Anglais (eng)
in Molecular Autism > 13 (2022) . - 52 p.
Mots-clés : Humans Male Child Autism Spectrum Disorder/diagnostic imaging Brain Mapping/methods Magnetic Resonance Imaging/methods Brain/diagnostic imaging Autistic Disorder Neural Pathways/diagnostic imaging Autism spectrum disorder Functional connectivity Functional magnetic resonance imaging Subtype k-means clustering Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental disorder with considerable clinical heterogeneity. This study aimed to explore the heterogeneity of ASD based on inter-individual heterogeneity of functional brain networks. METHODS: Resting-state functional magnetic resonance imaging data from the Autism Brain Imaging Data Exchange database were used in this study for 105 children with ASD and 102 demographically matched typical controls (TC) children. Functional connectivity (FC) networks were first obtained for ASD and TC groups, and inter-individual deviation of functional connectivity (IDFC) from the TC group was then calculated for each individual with ASD. A k-means clustering algorithm was used to obtain ASD subtypes based on IDFC patterns. The FC patterns were further compared between ASD subtypes and the TC group from the brain region, network, and whole-brain levels. The relationship between IDFC and the severity of clinical symptoms of ASD for ASD subtypes was also analyzed using a support vector regression model. RESULTS: Two ASD subtypes were identified based on the IDFC patterns. Compared with the TC group, the ASD subtype 1 group exhibited a hypoconnectivity pattern and the ASD subtype 2 group exhibited a hyperconnectivity pattern. IDFC for ASD subtype 1 and subtype 2 was found to predict the severity of social communication impairments and the severity of restricted and repetitive behaviors in ASD, respectively. LIMITATIONS: Only male children were selected for this study, which limits the ability to study the effects of gender and development on ASD heterogeneity. CONCLUSIONS: These results suggest the existence of subtypes with different FC patterns in ASD and provide insight into the complex pathophysiological mechanism of clinical manifestations of ASD. En ligne : http://dx.doi.org/10.1186/s13229-022-00535-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=491 Patterns of connectome variability in autism across five functional activation tasks: findings from the LEAP project / Tristan LOODEN in Molecular Autism, 13 (2022)
![]()
[article]
Titre : Patterns of connectome variability in autism across five functional activation tasks: findings from the LEAP project Type de document : Texte imprimé et/ou numérique Auteurs : Tristan LOODEN, Auteur ; Dorothea L. FLORIS, Auteur ; Alberto LLERA, Auteur ; Roselyne J. CHAUVIN, Auteur ; Tony CHARMAN, Auteur ; Tobias BANASCHEWSKI, Auteur ; Declan MURPHY, Auteur ; Andre F. MARQUAND, Auteur ; Jan K. BUITELAAR, Auteur ; Christian F. BECKMANN, Auteur ; AIMS-2-TRIALS GROUP, Auteur Article en page(s) : 53 p. Langues : Anglais (eng) Mots-clés : Autism Canonical correlation analysis Functional connectivity Heterogeneity Normative modeling fMRI Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (autism) is a complex neurodevelopmental condition with pronounced behavioral, cognitive, and neural heterogeneities across individuals. Here, our goal was to characterize heterogeneity in autism by identifying patterns of neural diversity as reflected in BOLD fMRI in the way individuals with autism engage with a varied array of cognitive tasks. METHODS: All analyses were based on the EU-AIMS/AIMS-2-TRIALS multisite Longitudinal European Autism Project (LEAP) with participants with autism (n=282) and typically developing (TD) controls (n=221) between 6 and 30Â years of age. We employed a novel task potency approach which combines the unique aspects of both resting state fMRI and task-fMRI to quantify task-induced variations in the functional connectome. Normative modelling was used to map atypicality of features on an individual basis with respect to their distribution in neurotypical control participants. We applied robust out-of-sample canonical correlation analysis (CCA) to relate connectome data to behavioral data. RESULTS: Deviation from the normative ranges of global functional connectivity was greater for individuals with autism compared to TD in each fMRI task paradigm (all tasks p< 0.001). The similarity across individuals of the deviation pattern was significantly increased in autistic relative to TD individuals (p< 0.002). The CCA identified significant and robust brain-behavior covariation between functional connectivity atypicality and autism-related behavioral features. CONCLUSIONS: Individuals with autism engage with tasks in a globally atypical way, but the particular spatial pattern of this atypicality is nevertheless similar across tasks. Atypicalities in the tasks originate mostly from prefrontal cortex and default mode network regions, but also speech and auditory networks. We show how sophisticated modeling methods such as task potency and normative modeling can be used toward unravelling complex heterogeneous conditions like autism. En ligne : http://dx.doi.org/10.1186/s13229-022-00529-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=491
in Molecular Autism > 13 (2022) . - 53 p.[article] Patterns of connectome variability in autism across five functional activation tasks: findings from the LEAP project [Texte imprimé et/ou numérique] / Tristan LOODEN, Auteur ; Dorothea L. FLORIS, Auteur ; Alberto LLERA, Auteur ; Roselyne J. CHAUVIN, Auteur ; Tony CHARMAN, Auteur ; Tobias BANASCHEWSKI, Auteur ; Declan MURPHY, Auteur ; Andre F. MARQUAND, Auteur ; Jan K. BUITELAAR, Auteur ; Christian F. BECKMANN, Auteur ; AIMS-2-TRIALS GROUP, Auteur . - 53 p.
Langues : Anglais (eng)
in Molecular Autism > 13 (2022) . - 53 p.
Mots-clés : Autism Canonical correlation analysis Functional connectivity Heterogeneity Normative modeling fMRI Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (autism) is a complex neurodevelopmental condition with pronounced behavioral, cognitive, and neural heterogeneities across individuals. Here, our goal was to characterize heterogeneity in autism by identifying patterns of neural diversity as reflected in BOLD fMRI in the way individuals with autism engage with a varied array of cognitive tasks. METHODS: All analyses were based on the EU-AIMS/AIMS-2-TRIALS multisite Longitudinal European Autism Project (LEAP) with participants with autism (n=282) and typically developing (TD) controls (n=221) between 6 and 30Â years of age. We employed a novel task potency approach which combines the unique aspects of both resting state fMRI and task-fMRI to quantify task-induced variations in the functional connectome. Normative modelling was used to map atypicality of features on an individual basis with respect to their distribution in neurotypical control participants. We applied robust out-of-sample canonical correlation analysis (CCA) to relate connectome data to behavioral data. RESULTS: Deviation from the normative ranges of global functional connectivity was greater for individuals with autism compared to TD in each fMRI task paradigm (all tasks p< 0.001). The similarity across individuals of the deviation pattern was significantly increased in autistic relative to TD individuals (p< 0.002). The CCA identified significant and robust brain-behavior covariation between functional connectivity atypicality and autism-related behavioral features. CONCLUSIONS: Individuals with autism engage with tasks in a globally atypical way, but the particular spatial pattern of this atypicality is nevertheless similar across tasks. Atypicalities in the tasks originate mostly from prefrontal cortex and default mode network regions, but also speech and auditory networks. We show how sophisticated modeling methods such as task potency and normative modeling can be used toward unravelling complex heterogeneous conditions like autism. En ligne : http://dx.doi.org/10.1186/s13229-022-00529-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=491