Familial risk of autism alters subcortical and cerebellar brain anatomy in infants and predicts the emergence of repetitive behaviors in early childhood / I. POTE in Autism Research, 12-4 (April 2019)  

Public ISBD [article]  inAutism Research > 12-4 (April 2019) . - p.614-627 Titre : Familial risk of autism alters subcortical and cerebellar brain anatomy in infants and predicts the emergence of repetitive behaviors in early childhood Type de document : Texte imprimé et/ou numérique Auteurs : I. POTE, Auteur ; S. WANG, Auteur ; V. SETHNA, Auteur ; A. BLASI, Auteur ; Eileen DALY, Auteur ; M. KUKLISOVA-MURGASOVA, Auteur ; S. LLOYD-FOX, Auteur ; E. MERCURE, Auteur ; P. BUSUULWA, Auteur ; V. STOENCHEVA, Auteur ; Tony CHARMAN, Auteur ; S. C. R. WILLIAMS, Auteur ; M. H. JOHNSON, Auteur ; D. G. M. MURPHY, Auteur ; G. M. MCALONAN, Auteur Article en page(s) : p.614-627 Langues : Anglais (eng) Mots-clés : autism spectrum disorder  cerebellum  familial risk  infants  magnetic resonance imaging-structural  mother-infant interaction  subcortex Index. décimale : PER Périodiques Résumé : Autism spectrum disorder (ASD) is a common neurodevelopmental condition, and infant siblings of children with ASD are at a higher risk of developing autistic traits or an ASD diagnosis, when compared to those with typically developing siblings. Reports of differences in brain anatomy and function in high-risk infants which predict later autistic behaviors are emerging, but although cerebellar and subcortical brain regions have been frequently implicated in ASD, no high-risk study has examined these regions. Therefore, in this study, we compared regional MRI volumes across the whole brain in 4-6-month-old infants with (high-risk, n = 24) and without (low-risk, n = 26) a sibling with ASD. Within the high-risk group, we also examined whether any regional differences observed were associated with autistic behaviors at 36 months. We found that high-risk infants had significantly larger cerebellar and subcortical volumes at 4-6-months of age, relative to low-risk infants; and that larger volumes in high-risk infants were linked to more repetitive behaviors at 36 months. Our preliminary observations require replication in longitudinal studies of larger samples. If correct, they suggest that the early subcortex and cerebellum volumes may be predictive biomarkers for childhood repetitive behaviors. Autism Res 2019, 12: 614-627. (c) 2019 The Authors. Autism Research published by International Society for Autism Research published byWiley Periodicals, Inc. LAY SUMMARY: Individuals with a family history of autism spectrum disorder (ASD) are at risk of ASD and related developmental difficulties. This study revealed that 4-6-month-old infants at high-risk of ASD have larger cerebellum and subcortical volumes than low-risk infants, and that larger volumes in high-risk infants are associated with more repetitive behaviors in childhood. En ligne : https://dx.doi.org/10.1002/aur.2083 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=388 [article] Familial risk of autism alters subcortical and cerebellar brain anatomy in infants and predicts the emergence of repetitive behaviors in early childhood [Texte imprimé et/ou numérique] / I. POTE, Auteur ; S. WANG, Auteur ; V. SETHNA, Auteur ; A. BLASI, Auteur ; Eileen DALY, Auteur ; M. KUKLISOVA-MURGASOVA, Auteur ; S. LLOYD-FOX, Auteur ; E. MERCURE, Auteur ; P. BUSUULWA, Auteur ; V. STOENCHEVA, Auteur ; Tony CHARMAN, Auteur ; S. C. R. WILLIAMS, Auteur ; M. H. JOHNSON, Auteur ; D. G. M. MURPHY, Auteur ; G. M. MCALONAN, Auteur . - p.614-627. Langues : Anglais (eng) in Autism Research > 12-4 (April 2019) . - p.614-627 Mots-clés : autism spectrum disorder  cerebellum  familial risk  infants  magnetic resonance imaging-structural  mother-infant interaction  subcortex Index. décimale : PER Périodiques Résumé : Autism spectrum disorder (ASD) is a common neurodevelopmental condition, and infant siblings of children with ASD are at a higher risk of developing autistic traits or an ASD diagnosis, when compared to those with typically developing siblings. Reports of differences in brain anatomy and function in high-risk infants which predict later autistic behaviors are emerging, but although cerebellar and subcortical brain regions have been frequently implicated in ASD, no high-risk study has examined these regions. Therefore, in this study, we compared regional MRI volumes across the whole brain in 4-6-month-old infants with (high-risk, n = 24) and without (low-risk, n = 26) a sibling with ASD. Within the high-risk group, we also examined whether any regional differences observed were associated with autistic behaviors at 36 months. We found that high-risk infants had significantly larger cerebellar and subcortical volumes at 4-6-months of age, relative to low-risk infants; and that larger volumes in high-risk infants were linked to more repetitive behaviors at 36 months. Our preliminary observations require replication in longitudinal studies of larger samples. If correct, they suggest that the early subcortex and cerebellum volumes may be predictive biomarkers for childhood repetitive behaviors. Autism Res 2019, 12: 614-627. (c) 2019 The Authors. Autism Research published by International Society for Autism Research published byWiley Periodicals, Inc. LAY SUMMARY: Individuals with a family history of autism spectrum disorder (ASD) are at risk of ASD and related developmental difficulties. This study revealed that 4-6-month-old infants at high-risk of ASD have larger cerebellum and subcortical volumes than low-risk infants, and that larger volumes in high-risk infants are associated with more repetitive behaviors in childhood. En ligne : https://dx.doi.org/10.1002/aur.2083 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=388

Modulation of atypical brain activation during executive functioning in autism: a pharmacological MRI study of tianeptine / R. H. WICHERS in Molecular Autism, 12 (2021)  

Public ISBD [article]  inMolecular Autism > 12 (2021) . - 14 p. Titre : Modulation of atypical brain activation during executive functioning in autism: a pharmacological MRI study of tianeptine Type de document : Texte imprimé et/ou numérique Auteurs : R. H. WICHERS, Auteur ; J. L. FINDON, Auteur ; A. JELSMA, Auteur ; V. GIAMPIETRO, Auteur ; V. STOENCHEVA, Auteur ; D. M. ROBERTSON, Auteur ; C. M. MURPHY, Auteur ; S. BLAINEY, Auteur ; G. MCALONAN, Auteur ; C. ECKER, Auteur ; K. RUBIA, Auteur ; D. G. M. MURPHY, Auteur ; Eileen DALY, Auteur Article en page(s) : 14 p. Langues : Anglais (eng) Mots-clés : Adult  Antidepressive Agents, Tricyclic/therapeutic use  Attention/drug effects  Autistic Disorder/diagnostic imaging/drug therapy/physiopathology/psychology  Brain/diagnostic imaging/physiopathology  Cross-Over Studies  Double-Blind Method  Executive Function/drug effects  Humans  Magnetic Resonance Imaging  Male  Middle Aged  Pilot Projects  Thiazepines/therapeutic use  Young Adult  Autism spectrum disorder  Executive functioning  Serotonin  Tianeptine  fMRI  grants from Lilly and Shire. The other authors declare that they have no competing  interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) is associated with deficits in executive functioning (EF), and these have been suggested to contribute to core as well as co-occurring psychiatric symptoms. The biological basis of these deficits is unknown but may include the serotonergic system, which is involved both in regulating EF in neurotypical populations and in the pathophysiology of ASD. We previously demonstrated that reducing serotonin by acute tryptophan depletion (ATD) shifts differences in brain function during performance of EF tasks towards control levels. However, ATD cannot be easily used in the clinic, and we therefore need to adopt alternative approaches to challenge the serotonin system. Hence, we investigated the role of the serotonergic modulator tianeptine on EF networks in ASD. METHOD: We conducted a pharmacological magnetic resonance imaging study, using a randomized double-blind crossover design, to compare the effect of an acute dosage of 12.5 mg tianeptine and placebo on brain activation during two EF tasks (of response inhibition and sustained attention) in 38 adult males: 19 with ASD and 19 matched controls. RESULTS: Under placebo, compared to controls, individuals with ASD had atypical brain activation in response inhibition regions including the inferior frontal cortex, premotor regions and cerebellum. During sustained attention, individuals with ASD had decreased brain activation in the right middle temporal cortex, right cuneus and left precuneus. Most of the case-control differences in brain function observed under placebo conditions were abolished by tianeptine administration. Also, within ASD individuals, brain functional differences were shifted significantly towards control levels during response inhibition in the inferior frontal and premotor cortices. LIMITATIONS: We conducted a pilot study using a single dose of tianeptine, and therefore, we cannot comment on long-term outcome. CONCLUSIONS: Our findings provide the first evidence that tianeptine can shift atypical brain activation during EF in adults with ASD towards control levels. Future studies should investigate whether this shift in the biology of ASD is maintained after prolonged treatment with tianeptine and whether it improves clinical symptoms. En ligne : http://dx.doi.org/10.1186/s13229-021-00422-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459 [article] Modulation of atypical brain activation during executive functioning in autism: a pharmacological MRI study of tianeptine [Texte imprimé et/ou numérique] / R. H. WICHERS, Auteur ; J. L. FINDON, Auteur ; A. JELSMA, Auteur ; V. GIAMPIETRO, Auteur ; V. STOENCHEVA, Auteur ; D. M. ROBERTSON, Auteur ; C. M. MURPHY, Auteur ; S. BLAINEY, Auteur ; G. MCALONAN, Auteur ; C. ECKER, Auteur ; K. RUBIA, Auteur ; D. G. M. MURPHY, Auteur ; Eileen DALY, Auteur . - 14 p. Langues : Anglais (eng) in Molecular Autism > 12 (2021) . - 14 p. Mots-clés : Adult  Antidepressive Agents, Tricyclic/therapeutic use  Attention/drug effects  Autistic Disorder/diagnostic imaging/drug therapy/physiopathology/psychology  Brain/diagnostic imaging/physiopathology  Cross-Over Studies  Double-Blind Method  Executive Function/drug effects  Humans  Magnetic Resonance Imaging  Male  Middle Aged  Pilot Projects  Thiazepines/therapeutic use  Young Adult  Autism spectrum disorder  Executive functioning  Serotonin  Tianeptine  fMRI  grants from Lilly and Shire. The other authors declare that they have no competing  interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) is associated with deficits in executive functioning (EF), and these have been suggested to contribute to core as well as co-occurring psychiatric symptoms. The biological basis of these deficits is unknown but may include the serotonergic system, which is involved both in regulating EF in neurotypical populations and in the pathophysiology of ASD. We previously demonstrated that reducing serotonin by acute tryptophan depletion (ATD) shifts differences in brain function during performance of EF tasks towards control levels. However, ATD cannot be easily used in the clinic, and we therefore need to adopt alternative approaches to challenge the serotonin system. Hence, we investigated the role of the serotonergic modulator tianeptine on EF networks in ASD. METHOD: We conducted a pharmacological magnetic resonance imaging study, using a randomized double-blind crossover design, to compare the effect of an acute dosage of 12.5 mg tianeptine and placebo on brain activation during two EF tasks (of response inhibition and sustained attention) in 38 adult males: 19 with ASD and 19 matched controls. RESULTS: Under placebo, compared to controls, individuals with ASD had atypical brain activation in response inhibition regions including the inferior frontal cortex, premotor regions and cerebellum. During sustained attention, individuals with ASD had decreased brain activation in the right middle temporal cortex, right cuneus and left precuneus. Most of the case-control differences in brain function observed under placebo conditions were abolished by tianeptine administration. Also, within ASD individuals, brain functional differences were shifted significantly towards control levels during response inhibition in the inferior frontal and premotor cortices. LIMITATIONS: We conducted a pilot study using a single dose of tianeptine, and therefore, we cannot comment on long-term outcome. CONCLUSIONS: Our findings provide the first evidence that tianeptine can shift atypical brain activation during EF in adults with ASD towards control levels. Future studies should investigate whether this shift in the biology of ASD is maintained after prolonged treatment with tianeptine and whether it improves clinical symptoms. En ligne : http://dx.doi.org/10.1186/s13229-021-00422-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459

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