1. Amoruso L, Finisguerra A, Urgesi C. {{Autistic traits predict poor integration between top-down contextual expectations and movement kinematics during action observation}}. {Scientific reports}. 2018; 8(1): 16208.
Autism is associated with difficulties in predicting and understanding other people’s actions. There is evidence that autistic traits are distributed across a spectrum and that subclinical forms of autistic impairments can also be measured in the typical population. To investigate the association between autistic traits and motor responses to others’ actions, we quantified these traits and measured cortico-spinal excitability modulations in M1 during the observation of actions embedded in congruent, incongruent and ambiguous contexts. In keeping with previous studies, we found that actions observed in congruent contexts elicited an early facilitation of M1 responses, and actions observed in incongruent contexts, resulted in a later inhibition. Correlational analysis revealed no association between autistic traits and the facilitation for congruent contexts. However, we found a significant correlation between motor inhibition and autistic traits, specifically related to social skills and attention to details. Importantly, the influence of these factors was independent from each other, and from the observer’s gender. Thus, results suggest that individuals with higher social deficits and greater detail-processing style are more impaired in suppressing action simulation in M1 when a mismatch between kinematics and context occurs. This points to difficult integration between kinematics and contextual representations in the autistic-like brain.
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2. Baker JK, Fenning RM, Howland MA, Huynh D. {{Parental criticism and behavior problems in children with autism spectrum disorder}}. {Autism : the international journal of research and practice}. 2018: 1362361318804190.
Associations between parent critical attitudes (a component of the Expressed Emotion construct) and behavior problems have been relatively well established in adolescents and young adults with autism spectrum disorder, but use of systems adapted for children with autism spectrum disorder and additional investigations with younger samples are needed. This study examined parental criticism, derived from a population-specific coding system, as related to behavior problems in children with autism spectrum disorder between the ages of 4 and 11 years, and considered parental warmth and children’s psychophysiological reactivity as statistical moderators of these associations. In all, 40 children with autism spectrum disorder and their primary caregivers attended a visit involving collection of child electrodermal activity, parent-child interaction, a parent interview from which critical attitudes and warmth were coded, and parent report of child behavior problems. Criticism was directly related to higher child externalizing but not internalizing problems. Parental criticism interacted with warmth in the prediction of internalizing problems such that criticism was only associated with more problems in the context of moderate but not high warmth. Criticism was positively associated with externalizing problems under conditions of moderate and high, but not low, child electrodermal activity reactivity. Implications for conceptualizations of parental criticism in autism spectrum disorder, for understanding comorbid behavior problems in this population, and for intervention are discussed.
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3. Balakrishnan S, Mironov SL. {{CA1 Neurons Acquire Rett Syndrome Phenotype After Brief Activation of Glutamatergic Receptors: Specific Role of mGluR1/5}}. {Frontiers in cellular neuroscience}. 2018; 12: 363.
Rett syndrome (RTT) is a neurological disorder caused by the mutation of the X-linked MECP2 gene. The neurophysiological hallmark of the RTT phenotype is the hyperexcitability of neurons made responsible for frequent epileptic attacks in the patients. Increased excitability in RTT might stem from impaired glutamate handling in RTT and its long-term consequences that has not been examined quantitatively. We recently reported (Balakrishnan and Mironov, 2018a,b) that the RTT hippocampus consistently demonstrates repetitive glutamate transients that parallel the burst firing in the CA1 neurons. We aimed to examine how brief stimulation of specific types of ionotropic and metabotropic glutamate receptors (GluR) can modulate the neuronal phenotype. We imaged glutamate with a fluorescence sensor (iGluSnFr) expressed in CA1 neurons in hippocampal organotypic slices from wild-type (WT) and Mecp2(-/y) mice (RTT). The neuronal and synaptic activities were assessed by patch-clamp and calcium imaging. In both WT and RTT slices, activation of AMPA, kainate, and NMDA receptors for 30 s first enhanced neuronal activity that induced a global release of glutamate. After transient augmentation of excitability and ambient glutamate, they subsided. After wash out of the agonists for 10 min, WT slices recovered and demonstrated repetitive glutamate transients, whose pattern resembled those observed in naive RTT slices. Hyperpolarization-activated (HCN) decreased and voltage-sensitive calcium channel (VSCC) currents increased. The effects were long-lasting and bigger in WT. We examined the role of mGluR1/5 in more detail. The effects of the agonist (S)-3,5-dihydroxyphenylglycine (DHPG) were the same as AMPA and NMDA and occluded by mGluR1/5 antagonists. Further modifications were examined using a non-stationary noise analysis of postsynaptic currents. The mean single channel current and their number at postsynapse increased after DHPG. We identified new channels as calcium-permeable AMPARs (CP-AMPAR). We then examined back-propagating potentials (bAPs) as a measure of postsynaptic integration. After bAPs, spontaneous afterdischarges were observed that lasted for approximately 2 min and were potentiated by DHPG. The effects were occluded by intracellular CP-AMPAR blocker and did not change after NMDAR blockade. We propose that brief elevations in ambient glutamate (through brief excitation with GluR agonists) specifically activate mGluR1/5. This modifies CP-AMPAR, HCN, and calcium conductances and makes neurons hyperexcitable. Induced changes can be further supported by repetitive glutamate transients established and serve to persistently maintain the aberrant neuronal RTT phenotype in the hippocampus.
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4. Brignell A, Chenausky KV, Song H, Zhu J, Suo C, Morgan AT. {{Communication interventions for autism spectrum disorder in minimally verbal children}}. {The Cochrane database of systematic reviews}. 2018; 11: Cd012324.
BACKGROUND: Autism spectrum disorder (ASD) has an estimated prevalence of around 1.7% of the population. People with ASD often also have language difficulties, and about 25% to 30% of children with ASD either fail to develop functional language or are minimally verbal. The ability to communicate effectively is an essential life skill, and difficulties with communication can have a range of adverse outcomes, including poorer academic achievement, behavioural difficulties and reduced quality of life. Historically, most studies have investigated communication interventions for ASD in verbal children. We cannot assume the same interventions will work for minimally verbal children with ASD. OBJECTIVES: To assess the effects of communication interventions for ASD in minimally verbal children. SEARCH METHODS: We searched CENTRAL, MEDLINE and Embase as well as 12 other databases and three trials registers in November 2017. We also checked the reference lists of all included studies and relevant reviews, contacting experts in the field as well as authors of identified studies about other potentially relevant ongoing and unpublished studies. SELECTION CRITERIA: Randomised controlled trials (RCTs) of communication-focused interventions for children (under 12 years of age) diagnosed with ASD and who are minimally verbal (fewer than 30 functional words or unable to use speech alone to communicate), compared with no treatment, wait-list control or treatment as usual. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. MAIN RESULTS: This review includes two RCTs (154 children aged 32 months to 11 years) of communication interventions for ASD in minimally verbal children compared with a control group (treatment as usual). One RCT used a verbally based intervention (focused playtime intervention; FPI) administered by parents in the home, whereas the other used an alternative and augmentative communication (AAC) intervention (Picture Exchange Communication System; PECS) administered by teachers in a school setting.The FPI study took place in the USA and included 70 participants (64 boys) aged 32 to 82 months who were minimally verbal and had received a diagnosis of ASD. This intervention focused on developing coordinated toy play between child and parent. Participants received 12 in-home parent training sessions for 90 minutes per session for 12 weeks, and they were also invited to attend parent advocacy coaching sessions. This study was funded by the National Institute of Child Health and Human Development, the MIND Institute Research Program and a Professional Staff Congress-City University of New York grant. The PECS study included 84 minimally verbal participants (73 boys) aged 4 to 11 years who had a formal diagnosis of ASD and who were not using PECS beyond phase 1 at baseline. All children attended autism-specific classes or units, and most classes had a child to adult ratio of 2:1. Teachers and parents received PECS training (two-day workshop). PECS consultants also conducted six half-day consultations with each class once per month over five months. This study took place in the UK and was funded by the Three Guineas Trust.Both included studies had high or unclear risk of bias in at least four of the seven ‘Risk of bias’ categories, with a lack of blinding for participants and personnel being the most problematic area. Using the GRADE approach, we rated the overall quality of the evidence as very low due to risk of bias, imprecision (small sample sizes and wide confidence intervals) and because there was only one trial identified per type of intervention (i.e. verbally based or AAC).Both studies focused primarily on communication outcomes (verbal and non-verbal). One of the studies also collected information on social communication. The FPI study found no significant improvement in spoken communication, measured using the expressive language domain of the Mullen Scale of Early Learning expressive language, at postintervention. However, this study found that children with lower expressive language at baseline (less than 11.3 months age-equivalent) improved more than children with better expressive language and that the intervention produced expressive language gains in some children. The PECS study found that children enrolled in the AAC intervention were significantly more likely to use verbal initiations and PECS symbols immediately postintervention; however, gains were not maintained 10 months later. There was no evidence that AAC improved frequency of speech, verbal expressive vocabulary or children’s social communication or pragmatic language immediately postintervention. Overall, neither of the interventions (PECS or FPI) resulted in maintained improvements in spoken or non-verbal communication in most children.Neither study collected information on adverse events, other communication skills, quality of life or behavioural outcomes. AUTHORS’ CONCLUSIONS: There is limited evidence that verbally based and ACC interventions improve spoken and non-verbal communication in minimally verbal children with ASD. A substantial number of studies have investigated communication interventions for minimally verbal children with ASD, yet only two studies met inclusion criteria for this review, and we considered the overall quality of the evidence to be very low. In the study that used an AAC intervention, there were significant gains in frequency of PECS use and verbal and non-verbal initiations, but not in expressive vocabulary or social communication immediately postintervention. In the study that investigated a verbally based intervention, there were no significant gains in expressive language postintervention, but children with lower expressive language at the beginning of the study improved more than those with better expressive language at baseline. Neither study investigated adverse events, other communication skills, quality of life or behavioural outcomes. Future RCTs that compare two interventions and include a control group will allow us to better understand treatment effects in the context of spontaneous maturation and will allow further comparison of different interventions as well as the investigation of moderating factors.
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5. Brown HK, Potvin LA, Lunsky Y, Vigod SN. {{Maternal Intellectual or Developmental Disability and Newborn Discharge to Protective Services}}. {Pediatrics}. 2018.
BACKGROUND: Approximately half of women with intellectual and developmental disabilities (IDDs) lose custody of their children at some point in their child’s development, but their rates of and risk factors for newborn discharge to child protective services from the birth hospitalization are relatively unknown. METHODS: We conducted a population-based study of newborns of 3845 women with IDDs and 379 834 women without IDDs in Ontario, Canada (2002-2012). We used modified Poisson regression to estimate adjusted relative risks (aRRs) and 95% confidence intervals (CIs) for discharge to child protective services directly from the birth hospitalization (1) comparing newborns of women with and without IDDs and (2) among newborns of women with IDDs according to sociodemographic, health, service, and perinatal characteristics. RESULTS: Approximately 5.7% of newborns of women with IDDs, compared with 0.2% of newborns of women without IDDs, were discharged to child protective services (aRR 8.10; 95% CI 6.51-10.09). Among newborns of women with IDDs, risk factors were maternal psychotic disorder (aRR 2.58; 95% CI 1.90-3.50), social assistance receipt (aRR 2.55; 95% CI 1.87-3.47), failure to receive an ultrasound by 20 weeks’ gestation (aRR 1.76; 95% CI 1.32-2.34), and receipt of <4 prenatal visits by 36 weeks' gestation (aRR 1.71; 95% CI 1.05-2.78). CONCLUSIONS: Although women with IDDs are at risk for custody loss immediately postdelivery, certain subgroups are at higher risk than others. Women with vulnerabilities related to comorbid psychotic disorders, poverty, and inadequate prenatal care may benefit from tailored, behavior-based parenting interventions before and during pregnancy to prevent maternal-newborn separations. Lien vers le texte intégral (Open Access ou abonnement)
6. Charman T. {{Mapping Early Symptom Trajectories in Autism Spectrum Disorder: Lessons and Challenges for Clinical Practice and Science}}. {Journal of the American Academy of Child and Adolescent Psychiatry}. 2018; 57(11): 820-1.
Variability in the trajectory of clinical symptoms in the early emerging presentation of young children with autism spectrum disorder (ASD) exists within an individual child over time and between different children at any point in time and across time. Georgiades et al.(1) recently coined the term « chronogeneity » to indicate these within- and between-participant patterns of variability over time. In clinical practice, this is often the focus of questions that parents ask clinicians at or soon after diagnosis: « Can you tell us what the future holds and will his (her) symptoms improve or get worse? » The variability or heterogeneity within and between children on the autism spectrum makes that a tough question to answer, however well one understands the motivation of the parent or caregiver in asking it.
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7. Delbruck E, Yang M, Yassine A, Grossman ED. {{Functional connectivity in ASD: Atypical pathways in brain networks supporting action observation and joint attention}}. {Brain research}. 2018.
Autism Spectrum Disorder (ASD) is a developmental disorder characterized by impaired social communication, including attending to and interpreting social cues, initiating and responding to joint attention, and engaging in abstract social cognitive reasoning. Current studies emphasize a underconnectivity in ASD, particularly for brain systems that support abstract social reasoning and introspective thought. Here, we evaluate intrinsic connectivity in children with ASD, targeting brain systems that support the developmental precursors to social reasoning, namely perception of social cues and joint attention. Using resting state fMRI made available through the Autism Brain Imaging Data Exchange (ABIDE), we compute functional connectivity within and between nodes in the action observation, attention and social cognitive networks in children and adolescents with ASD. We also compare connectivity strength to observational assessments that explicitly evaluate severity of ASD on two distinct subdomains using the ADOS-Revised schedule: social affective (SA) and restricted, repetitive behaviors (RRB). Compared to age-matched controls, children with ASD have decreased functional connectivity in a number of connections in the action observation network, particularly in the lateral occipital cortex (LOTC) and fusiform gyrus (FG). Distinct patterns of connections were also correlated with symptom severity on the two subdomains of the ADOS. ADOS-SA severity most strongly correlated with connectivity to the left TPJ, while ADOS-RRB severity correlated with connectivity to the dMPFC. We conclude that atypical connectivity in the action observation system may underlie some of the more complex deficits in social cognitive systems in ASD.
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8. Delli CKS, Polychronopoulou SA, Kolaitis GA, Antoniou AG. {{Review of interventions for the management of anxiety symptoms in children with ASD}}. {Neuroscience and biobehavioral reviews}. 2018.
BACKGROUND: Anxiety isa common accompanying symptom in people with Autism Spectrum Disorder (ASD). OBJECTIVES: To investigate interventions available for the management of anxietyin children with ASD internationally. METHODS: Review was made of relevant studies found through PubMed, the National Institute of Health (NIH) publications and resources in the libraries of the University of Macedoniaand the Greek NationalResearch Foundation. RESULTS: Of the372 studiesretrieveddealing withinterventionsfor children with ASD who have anxiety disorders published from the 1980s to 2017, 137 were included in this review.Interventions includepharmacological intervention, cognitive behavioral therapy(CBT),socialrecreational (SR)programs,other psychosocial therapies, teaching social skillsand combinations of educational, psychological and medical treatment. CONCLUSIONS: Various methods for coping with anxiety in children with ASD have been applied,including pharmacotherapy, psychosocial andCBT interventions, parent education and school-based programs. A combination of approachesshould be selected,based onassessment of each child’s particular characteristics.
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9. Deneault E, White SH, Rodrigues DC, Ross PJ, Faheem M, Zaslavsky K, Wang Z, Alexandrova R, Pellecchia G, Wei W, Piekna A, Kaur G, Howe JL, Kwan V, Thiruvahindrapuram B, Walker S, Lionel AC, Pasceri P, Merico D, Yuen RKC, Singh KK, Ellis J, Scherer SW. {{Complete Disruption of Autism-Susceptibility Genes by Gene Editing Predominantly Reduces Functional Connectivity of Isogenic Human Neurons}}. {Stem cell reports}. 2018.
Autism spectrum disorder (ASD) is phenotypically and genetically heterogeneous. We present a CRISPR gene editing strategy to insert a protein tag and premature termination sites creating an induced pluripotent stem cell (iPSC) knockout resource for functional studies of ten ASD-relevant genes (AFF2/FMR2, ANOS1, ASTN2, ATRX, CACNA1C, CHD8, DLGAP2, KCNQ2, SCN2A, TENM1). Neurogenin 2 (NGN2)-directed induction of iPSCs allowed production of excitatory neurons, and mutant proteins were not detectable. RNA sequencing revealed convergence of several neuronal networks. Using both patch-clamp and multi-electrode array approaches, the electrophysiological deficits measured were distinct for different mutations. However, they culminated in a consistent reduction in synaptic activity, including reduced spontaneous excitatory postsynaptic current frequencies in AFF2/FMR2-, ASTN2-, ATRX-, KCNQ2-, and SCN2A-null neurons. Despite ASD susceptibility genes belonging to different gene ontologies, isogenic stem cell resources can reveal common functional phenotypes, such as reduced functional connectivity.
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10. Faja S, Nelson Darling L. {{Variation in restricted and repetitive behaviors and interests relates to inhibitory control and shifting in children with autism spectrum disorder}}. {Autism : the international journal of research and practice}. 2018: 1362361318804192.
Symptoms of restricted and repetitive behaviors and interests in autism are theoretically linked to executive functioning, which includes problem-solving abilities such as inhibition and cognitive flexibility. This study examined whether inhibition and flexibility are related to higher order restricted and repetitive behaviors and interests (e.g. circumscribed interests and ritualistic behavior) and sensorimotor behaviors (e.g. stereotyped and repetitive movements and sensory preoccupations) among 102 school-aged children with autism spectrum disorder who had cognitive abilities in the average or above average range. The ability to inhibit interfering information and shifting ability were related to higher order restricted and repetitive behaviors and interests, and each uniquely accounted for variance. This suggests that the ability to suppress interfering information as well as the ability to flexibly shift between patterns of responding is protective against higher order restricted and repetitive behaviors and interest symptoms in autism. In addition, the ability to proactively slow one’s reaction time in order to respond more carefully was related to sensorimotor restricted and repetitive behaviors. These results support the importance of distinguishing between higher order and sensorimotor symptoms due to their distinct relationships to executive functioning abilities.
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11. Frazier TW, Klingemier EW, Parikh S, Speer L, Strauss MS, Eng C, Hardan AY, Youngstrom EA. {{Development and Validation of Objective and Quantitative Eye Tracking-Based Measures of Autism Risk and Symptom Levels}}. {Journal of the American Academy of Child and Adolescent Psychiatry}. 2018; 57(11): 858-66.
OBJECTIVE: The primary aim of this study was to develop and validate eye tracking-based measures for estimating autism spectrum disorder (ASD) risk and quantifying autism symptom levels. METHOD: Eye tracking data were collected from youth during an initial evaluation visit, with administrators blinded to all clinical information. Consensus diagnoses were given by the multidisciplinary team. Participants viewed a 5-minute video that included 44 dynamic stimuli from 7 distinct paradigms while gaze was recorded. Gaze metrics were computed for temporally defined regions of interest. Autism risk and symptom indices aggregated gaze measures showing significant bivariate relationships with ASD diagnosis and Autism Diagnostic Observation Schedule, Second Edition (ADOS-2) symptom severity levels in a training sample (75%, n = 150). Receiver operating characteristic curve analysis and nonparametric correlations were used to cross-validate findings in a test sample (25%; n = 51). RESULTS: Most children (n = 201, 92%) completed a valid eye tracking assessment (ages 1.6 horizontal line 17.6; 80% male; ASD n = 91, non-ASD n = 110). In the test subsample, the autism risk index had high accuracy for ASD diagnosis (area under the curve [AUC] = 0.86, 95% CI =0.75-0.95), whereas the autism symptom index was strongly associated with ADOS-2 total severity scores (r = 0.41, p < .001). Validity was not substantively attenuated after adjustment for language, nonverbal cognitive ability, or other psychopathology symptoms (r = 0.40-0.67, p > .001). CONCLUSION: Eye tracking measures appear to be useful quantitative, objective measures of ASD risk and autism symptom levels. If independently replicated and scaled for clinical use, eye tracking-based measures could be used to inform clinical judgment regarding ASD identification and to track autism symptom levels.
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12. Fusaroli R, Weed E, Fein D, Naigles L. {{Hearing me hearing you: Reciprocal effects between child and parent language in autism and typical development}}. {Cognition}. 2018; 183: 1-18.
Language development in typically developing children (TD) has traditionally been investigated in relation to environmental factors, while language in children with autism spectrum disorder (ASD) has primarily been related to child-based factors. We employ a longitudinal corpus of 32 preschoolers with ASD and 35 linguistically matched TD peers recorded over 6 visits (ranging between 2 and 5years of age) to investigate the relative importance of child-based and environmental factors in language development for both populations. We also investigate the reciprocal interaction between children’s response to parents’ input, and parents’ response to children’s production. We report six major findings. (1) Children’s production of word types, tokens, and MLU increased across visits, and were predicted by their Expressive Language (EL) (positively) and diagnosis (negatively) from Visit 1. (2) Parents’ production also increased across visits, and was predicted by their child’s nonverbal cognition (positively) and diagnosis (negatively) from Visit 1. (3) At all visits and across groups, children and parents matched each other in lexical and syntactic production; (4) Parents who produced longer MLUs during a given visit had children who produced more word types and tokens, and had longer MLUs, at the subsequent visit. (5) When both child EL at Visit 1 and parent MLU were included in the model, both contributed significantly to future child language; however, EL accounted for a greater proportion of the variance. (6) Finally, children’s speech significantly predicted parent speech at the next visit. Taken together, these results draw more attention to the importance of child-based factors in the early language development of TD children, and to the importance of parental language factors in the early language development of children with ASD.
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13. Gandaglia A, Brivio E, Carli S, Palmieri M, Bedogni F, Stefanelli G, Bergo A, Leva B, Cattaneo C, Pizzamiglio L, Cicerone M, Bianchi V, Kilstrup-Nielsen C, D’Annessa I, Di Marino D, D’Adamo P, Antonucci F, Frasca A, Landsberger N. {{A Novel Mecp2(Y120D) Knock-in Model Displays Similar Behavioral Traits But Distinct Molecular Features Compared to the Mecp2-Null Mouse Implying Precision Medicine for the Treatment of Rett Syndrome}}. {Molecular neurobiology}. 2018.
MeCP2 is a fundamental protein associated with several neurological disorders, including Rett syndrome. It is considered a multifunctional factor with a prominent role in regulating chromatin structure; however, a full comprehension of the consequences of its deficiency is still lacking. Here, we characterize a novel mouse model of Mecp2 bearing the human mutation Y120D, which is localized in the methyl-binding domain. As most models of Mecp2, the Mecp2(Y120D) mouse develops a severe Rett-like phenotype. This mutation alters the interaction of the protein with chromatin, but surprisingly, it also impairs its association with corepressors independently on the involved interacting domains. These features, which become overt mainly in the mature brain, cause a more accessible and transcriptionally active chromatin structure; conversely, in the Mecp2-null brain, we find a less accessible and transcriptionally inactive chromatin. By demonstrating that different MECP2 mutations can produce concordant neurological phenotypes but discordant molecular features, we highlight the importance of considering personalized approaches for the treatment of Rett syndrome.
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14. Gonatopoulos-Pournatzis T, Wu M, Braunschweig U, Roth J, Han H, Best AJ, Raj B, Aregger M, O’Hanlon D, Ellis JD, Calarco JA, Moffat J, Gingras AC, Blencowe BJ. {{Genome-wide CRISPR-Cas9 Interrogation of Splicing Networks Reveals a Mechanism for Recognition of Autism-Misregulated Neuronal Microexons}}. {Molecular cell}. 2018; 72(3): 510-24.e12.
Alternative splicing is crucial for diverse cellular, developmental, and pathological processes. However, the full networks of factors that control individual splicing events are not known. Here, we describe a CRISPR-based strategy for the genome-wide elucidation of pathways that control splicing and apply it to microexons with important functions in nervous system development and that are commonly misregulated in autism. Approximately 200 genes associated with functionally diverse regulatory layers and enriched in genetic links to autism control neuronal microexons. Remarkably, the widely expressed RNA binding proteins Srsf11 and Rnps1 directly, preferentially, and frequently co-activate these microexons. These factors form critical interactions with the neuronal splicing regulator Srrm4 and a bi-partite intronic splicing enhancer element to promote spliceosome formation. Our study thus presents a versatile system for the identification of entire splicing regulatory pathways and further reveals a common mechanism for the definition of neuronal microexons that is disrupted in autism.
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15. Kang E, McPartland JC, Keifer CM, Foss-Feig JH, Levy EJ, Lerner MD. {{Reply to: Can the N170 Be Used as an Electrophysiological Biomarker Indexing Face Processing Difficulties in Autism Spectrum Disorder?}}. {Biological psychiatry Cognitive neuroscience and neuroimaging}. 2018.
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16. Kim SH, Bal VH, Benrey N, Choi YB, Guthrie W, Colombi C, Lord C. {{Variability in Autism Symptom Trajectories Using Repeated Observations From 14 to 36 Months of Age}}. {Journal of the American Academy of Child and Adolescent Psychiatry}. 2018; 57(11): 837-48.e2.
OBJECTIVE: This study examined variability in autism symptom trajectories in toddlers referred for possible autism spectrum disorder (ASD) who had frequent observations from 14 to 36 months of age. METHOD: In total, 912 observations of the Autism Diagnostic Observation Schedule (ADOS) were obtained from 149 children (103 with ASD) followed from 14 to 36 months of age. As a follow-up to a previous analysis of ADOS algorithm scores, a different analytic approach (Proc Traj) was implemented to identify several courses of symptom trajectories using ADOS Calibrated Severity Scores in a larger sample. Proc Traj is a statistical method that clusters individuals into separate groups based on different growth trajectories. Changes in symptom severity based on individual ADOS items also were examined. RESULTS: Trajectory analysis of overall symptom severity identified 4 clusters (non-spectrum approximately 25%; worsening approximately 27%; moderately-improving approximately 25%; severe-persistent approximately 23%). Trajectory clusters varied significantly in the proportions of confirmatory ASD diagnosis, level of baseline and final verbal and nonverbal abilities, and symptom severity. For the moderately-improving group, social communication improved, whereas restricted and repetitive behaviors were stable over time. Language and verbal and nonverbal communication improved for many children, but several social affect and restricted and repetitive behavior symptoms remained stable or worsened. CONCLUSION: Significant variability in symptom trajectories was observed among toddlers referred for possible ASD. Changes in social and restricted and repetitive behavior domain scores did not always co-occur. Similarly, item-level trajectories did not always align with trajectories of overall severity scores. These findings highlight the importance of monitoring individual symptoms within broader symptom domains when conducting repeated assessments for young children with suspected ASD.
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17. Kruppa JA, Gossen A, Weiss EO, Kohls G, Grossheinrich N, Cholemkery H, Freitag CM, Karges W, Wolfle E, Sinzig J, Fink GR, Herpertz-Dahlmann B, Konrad K, Schulte-Ruther M. {{Neural modulation of social reinforcement learning by intranasal oxytocin in male adults with high-functioning autism spectrum disorder: a randomized trial}}. {Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology}. 2018.
Reduced social motivation is a hallmark of individuals with autism spectrum disorders (ASDs). Although the exact neural mechanisms are unclear, oxytocin has been shown to enhance motivation and attention to social stimuli, suggesting a potential to augment social reinforcement learning as the central mechanism of behavioral interventions in ASD. We tested how reinforcement learning in social contexts and associated reward prediction error (RPE) signals in the nucleus accumbens (NAcc) were modulated by intranasal oxytocin. Male adults with a childhood diagnosis of ASD (n = 15) and healthy controls (n = 24; aged 18-26 years) performed a probabilistic reinforcement learning task during functional magnetic resonance imaging in a single-center (research center in Germany), randomized double-blind, placebo-controlled cross-over trial. The interventions were intranasal oxytocin (Syntocinon((R)), Novartis; 10 puffs = 20 international units (IUs) per treatment) and placebo spray. Using computational modeling of behavioral data, trial-by-trial RPE signals were assessed and related to brain activation in NAcc during reinforcing feedback in social and non-social contexts. The order of oxytocin/placebo was randomized for 60 participants. Twenty-one participants were excluded from analyses, leaving 39 for the final analysis. Behaviorally, individuals with ASD showed enhanced learning under oxytocin when the learning target as well as feedback was social as compared to non-social (social vs. non-social target: 87.09% vs. 71.29%, 95% confidence interval (CI): 7.28-24.33, p = .003; social vs. non-social feedback: 81.00% vs. 71.29%, 95% CI: 2.81-16.61, p = .027). Correspondingly, oxytocin enhanced the correlation of the RPE signal with NAcc activation during social (vs. non-social) feedback in ASD (3.48 vs. -1.12, respectively, 95% CI: 2.98-6.22, p = .000), whereas in controls, this effect was found in the placebo condition (2.90 vs. -1.14, respectively, 95% CI: 1.07-7.01, p = 0.010). In ASD, a similar pattern emerged when the learning target was social (3.00 vs. -0.64, respectively, 95% CI: -0.13 to 7.41, p = 0.057), whereas controls showed a reduced correlation for social learning targets under oxytocin (-0.70 vs. 2.72, respectively, 95% CI: -5.86 to 0.98, p = 0.008). The current data suggest that intranasal oxytocin has the potential to enhance social reinforcement learning in ASD. Future studies are warranted that investigate whether oxytocin can potentiate social learning when combined with behavioral therapies, resulting in greater treatment benefits than traditional behavior-only approaches.
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18. Laplante DP, Simcock G, Cao-Lei L, Mouallem M, Elgbeili G, Brunet A, Cobham V, Kildea S, King S. {{The 5-HTTLPR polymorphism of the serotonin transporter gene and child’s sex moderate the relationship between disaster-related prenatal maternal stress and autism spectrum disorder traits: The QF2011 Queensland flood study}}. {Development and psychopathology}. 2018: 1-15.
The 5-HTTLPR polymorphism of the serotonin transporter has been shown to play a role in autism spectrum disorders (ASD). Moreover, disaster-related prenatal maternal stress (PNMS) has also been shown to be associated with ASD. However, no study to date has examined whether these two factors, either individually or in combination, are predictive of ASD traits in the same sample. We hypothesized that children, particularly boys, with the LL genotype exposed to high levels of disaster-related PNMS would exhibit higher levels of ASD traits compared to boys with the LS or SS genotypes and girls regardless of genotype. Genotype and ASD levels obtained using the Australian normed Autism Spectrum Rating Scales – Short Form were available for 105 30-month-old children exposed to varying levels of PNMS following the 2011 Queensland Flood. For boys, higher ASD traits were associated with the 5-HTTLPR LL genotype in combination with either a negative maternal appraisal of the flood, or high levels of maternal composite subjective stress, PSTD-like or peritraumatic dissociation symptoms. For girls, maternal peritraumatic dissociation levels in combination with the 5-HTTLPR LS or SS genotype were associated with higher ASD traits. The present findings are the first to demonstrate that children’s genotype moderates effects of disaster-related PNMS on ASD traits, with different pattern according to child sex.
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19. Liddle M, Birkett K, Bonjour A, Risma K. {{A Collaborative Approach to Improving Health Care for Children With Developmental Disabilities}}. {Pediatrics}. 2018.
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20. Lord C. {{For Better or for Worse? Later Diagnoses of Autism Spectrum Disorder in Some Younger Siblings of Already Diagnosed Children}}. {Journal of the American Academy of Child and Adolescent Psychiatry}. 2018; 57(11): 822-3.
Later diagnoses of autism spectrum disorder (ASD) represent a theoretical challenge for researchers, including myself, who have conceived of ASD as a very early arising developmental disorder that affects learning and behavior from infancy onward.(1) Such diagnoses also are a concern because of disparities in access to early intervention, which we know are associated with ethnic minority status and less parental education.(2) If we believe that early intervention makes a difference, then finding children with ASD who cannot be identified until early school age is problematic. Three recent studies, before the present study by Ozonoff et al.,(3) found relatively small, but not insignificant, numbers of children who were not diagnosed until after 6 years of age.(4-6) The present study by Ozonoff et al.(3) uses the opportunity provided by a unique prospective dataset of younger siblings of children with autism (often referred to as the Baby Siblings Research Consortium) to describe 14 children who had not been identified as having ASD at 3 years of age, despite detailed early assessments by a skilled research team, out of 113 children who received ASD diagnoses in middle childhood.
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21. Macari S, DiNicola L, Kane-Grade F, Prince E, Vernetti A, Powell K, Fontenelle St, Chawarska K. {{Emotional Expressivity in Toddlers With Autism Spectrum Disorder}}. {Journal of the American Academy of Child and Adolescent Psychiatry}. 2018; 57(11): 828-36.e2.
OBJECTIVE: There is a prevailing notion that children with autism spectrum disorder (ASD) exhibit intense negative and attenuated positive emotions, although the empirical evidence regarding their emotional expressiveness (EE) is limited. Given the importance of emotions in shaping social and cognitive development, we examined intensity and valence of EE and links between EE and autism severity and parent-reported temperament in ASD. METHOD: Toddlers (aged 21.2 months) with ASD (n = 43), developmental delay (DD, n = 16), and typical development (TD, n = 40) underwent standardized probes designed to induce anger, joy, and fear. Intensity of EE through facial and vocal channels were coded offline. Autism severity and temperament were quantified using the Autism Diagnostic Observation Schedule-2 (ADOS-2) and Early Childhood Behavior Questionnaire (ECBQ). RESULTS: The ASD group exhibited less intense fear compared to both the DD and TD groups, more intense anger than DD but not TD, with no differences in joy intensity. All groups showed similar levels of incongruous negative EE. Intensity of fear and anger were not associated with severity of autism symptoms, but lower intensity of joy was related to greater autism severity. Expressed fear and joy were associated with temperament. CONCLUSION: The study provides no support for a negative emotionality bias in ASD. Instead, toddlers with ASD display a muted response to threat and an accentuated response to goal blockage, whereas the ability to express positive emotions appears intact. Negative emotionality and social disability dimensions are independent. The study demonstrates the complexity of EE in ASD and motivates investigations into underlying mechanisms as well as its role in shaping complex phenotypes of affected children.
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22. Manor-Binyamini I. {{Listening to Bedouin fathers of children with autism spectrum disorder}}. {Transcultural psychiatry}. 2018: 1363461518808148.
Although children across the world experience autism spectrum disorder (ASD), most research on ASD has been conducted using Western cultural perspectives and has focused primarily on mothers, leaving significant gaps in the literature. This study aimed to address these gaps by exploring the experiences of fathers raising children with ASD in a Bedouin community. To this end, a sample of 19 fathers of children (aged 6-15 years) with ASD living in recognized and unrecognized Bedouin settlements in the Negev participated in ethnographic, semi-structured interviews designed to investigate their experiences with raising a child with ASD in their community. Two major themes emerged: the challenges that Bedouin fathers of children with ASD face, and the influence of socio-demographic and cultural characteristics on their experience. Findings reflect the complex experiences of fathers raising children with ASD in the Bedouin community, stemming from their socio-cultural context and the limited knowledge and support services that are available in the community for these children. This article concludes with recommendations on how to enhance professional sensitivity and provide more culturally tailored services for parents of children with ASD.
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23. Montgomery AK, Shuffrey LC, Guter SJ, Anderson GM, Jacob S, Mosconi MW, Sweeney JA, Turner JB, Sutcliffe JS, Cook EH, Jr., Veenstra-VanderWeele J. {{Maternal Serotonin Levels Are Associated With Cognitive Ability and Core Symptoms in Autism Spectrum Disorder}}. {Journal of the American Academy of Child and Adolescent Psychiatry}. 2018; 57(11): 867-75.
OBJECTIVE: The serotonin (5-hydroxytryptamine [HT]) system has long been implicated in autism spectrum disorder (ASD). Whole-blood 5-HT level (WB5-HT) is a stable, heritable biomarker that is elevated in more than 25% of children with ASD. Recent findings indicate that the maternal 5-HT system may influence embryonic neurodevelopment, but maternal WB5-HT has not been examined in relation to ASD phenotypes. METHOD: WB5-HT levels were obtained from 181 individuals (3-27 years of age) diagnosed with ASD, 99 of their fathers, and 119 of their mothers. Standardized assessments were used to evaluate cognitive, behavioral, and language phenotypes. RESULTS: Exploratory regression analyses found relationships between maternal WB5-HT and nonverbal IQ (NVIQ), Autism Diagnostic Interview-Revised (ADI-R) Nonverbal Communication Algorithm scores, and overall adaptive function on the Vineland Adaptive Behavior Scales-II. Latent class analysis identified a three-class structure in the assessment data, describing children with low, intermediate, and high severity across measures of behavior, cognition, and adaptive function. Mean maternal WB5-HT differed across classes, with the lowest maternal WB5-HT levels seen in the highest-severity group (Welch F2,46.048 = 17.394, p < .001). Paternal and proband WB5-HT did not differ between classes. CONCLUSION: Maternal WB5-HT is associated with neurodevelopmental outcomes in offspring with ASD. Prospective, longitudinal studies will be needed to better understand the relationship between the function of the maternal serotonin system during pregnancy and brain development. Further studies in animal models may be able to reveal the mechanisms underlying these findings. Lien vers le texte intégral (Open Access ou abonnement)
24. Monuteaux MC. {{Methodological Challenges in Studying Autism Spectrum Disorder}}. {Journal of the American Academy of Child and Adolescent Psychiatry}. 2018; 57(11): 824-5.
Evidence from genetic, animal, and epidemiologic studies have consistently implicated the serotonin (5-HT) system as an important risk factor for autism spectrum disorder (ASD).(1) Hyperserotonemia has been documented in more than 25% of pediatric ASD cases.(2) Although serotonergic functioning is a plausible and tantalizing component of causal models of ASD pathophysiology, specific mechanisms remain poorly understood.(2) Barriers to delineating these mechanisms include the difficulty of disentangling the effects of genetic risks, environmental exposures across development (including gestational exposure to selective 5-HT reuptake inhibitors),(3) and the possible interactions between these factors in a population with considerable phenotypic and prognostic heterogeneity.
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25. Muller RA, Fishman I. {{Brain Connectivity and Neuroimaging of Social Networks in Autism}}. {Trends in cognitive sciences}. 2018.
Impairments in social communication (SC) predominate among the core diagnostic features of autism spectrum disorders (ASDs). Neuroimaging has revealed numerous findings of atypical activity and connectivity of ‘social brain’ networks, yet no consensus view on crucial developmental causes of SC deficits has emerged. Aside from methodological challenges, the deeper problem concerns the clinical label of ASD. While genetic studies have not comprehensively explained the causes of nonsyndromic ASDs, they highlight that the clinical label encompasses many etiologically different disorders. The question of how potential causes and etiologies converge onto a comparatively narrow set of SC deficits remains. Only neuroimaging designs searching for subtypes within ASD cohorts (rather than conventional group level designs) can provide translationally informative answers.
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26. Ousset A, Bassand C, Chavez PF, Meeus J, Robin F, Schubert MA, Somville P, Dodou K. {{Development of a small-scale spray-drying approach for amorphous solid dispersions (ASDs) screening in early drug development}}. {Pharmaceutical development and technology}. 2018: 1-15.
The present study details the development of a small-scale spray-drying approach for the routine screening of amorphous solid dispersions (ASDs). This strategy aims to overcome the limitations of standard screening methodologies like solvent casting and quench cooling to predict drug-polymer miscibility of spray-dried solid dispersions (SDSDs) and therefore to guarantee appropriate carrier and drug-loading (DL) selection. A DoE approach was conducted to optimize process conditions of ProCept 4M8-TriX spray-drying to maximize the yield from a 100 mg batch of Itraconazole/HPMCAS-LF and Itraconazole/Soluplus 40:60 (w/w). Optimized process parameters include: inlet temperature, pump speed, drying and atomizing airflows. Identified process conditions derived from the DoE analysis were further (i) tested with Itraconazole, Naproxen and seven polymers, (ii) adapted for small cyclone use, (iii) downscaled to 20 mg batch production. Drug-polymer miscibility was systematically characterized using modulated differential scanning calorimetry (mDSC). Spray-drying was identified as a well-suited screening approach: mean yield of 10.1 to 40.6% and 51.1 to 81.0% were obtained for 20 and 100 mg ASD productions, respectively. Additionally, this work demonstrates the interest to move beyond conventional screening approaches and integrate spray-drying during screening phases so that a greater prediction accuracy in terms of SDSDs miscibility and performance can be obtained.
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27. Ozonoff S, Young GS, Brian J, Charman T, Shephard E, Solish A, Zwaigenbaum L. {{Diagnosis of Autism Spectrum Disorder After Age 5 in Children Evaluated Longitudinally Since Infancy}}. {Journal of the American Academy of Child and Adolescent Psychiatry}. 2018; 57(11): 849-57.e2.
OBJECTIVE: The diagnosis of autism spectrum disorder (ASD) has been found to be remarkably stable but few studies have followed children not initially diagnosed with ASD beyond 3 years of age to examine late or delayed diagnoses. The present study used a prospective familial-risk design to identify children who had undergone multiple comprehensive assessments in preschool and were determined to be negative for ASD only to meet criteria for ASD when tested in middle childhood. METHOD: Data were pooled across 3 research teams studying later-born siblings of children with ASD. Fourteen children met inclusion criteria for the late-diagnosed group and were compared with a large sample of high- and low-risk siblings from the same sites who had ASD or typical development (TD) outcomes at 3 years of age. RESULTS: As a group, the late-diagnosed children scored between the TD and ASD groups on most measures administered at 3 years and differed significantly from the ASD group on most measures. However, there was significant heterogeneity among the late-diagnosed cases. Seven showed very little evidence of ASD in preschool, whereas 7 demonstrated subtle, subthreshold symptomatology. CONCLUSION: Some children with ASD might present with a subtle phenotype early in life or show a prolonged time course of symptom development. This emphasizes the need for screening and surveillance schedules that extend past 36 months and continued evaluation of any child who presents with atypical early development and/or high-risk status. The findings also shed light on reasons why the mean age of ASD diagnosis remains older than 4 years.
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28. Quesnel-Vallieres M, Weatheritt RJ, Cordes SP, Blencowe BJ. {{Autism spectrum disorder: insights into convergent mechanisms from transcriptomics}}. {Nature reviews Genetics}. 2018.
Heredity has a major role in autism spectrum disorder (ASD), yet underlying causal genetic variants have been defined only in a fairly small subset of cases. The enormous genetic heterogeneity associated with ASD emphasizes the importance of identifying convergent pathways and molecular mechanisms that are responsible for this disorder. We review how recent transcriptomic analyses have transformed our understanding of pathway convergence in ASD. In particular, deep RNA sequencing coupled with downstream investigations has revealed that a substantial fraction of autistic brains possess distinct transcriptomic signatures. These signatures are in part a consequence of altered neuronal activity and have a particular impact on pre-mRNA alternative splicing patterns.
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29. Saldarriaga W, Salcedo-Arellano MJ, Rodriguez-Guerrero T, Rios M, Fandino-Losada A, Ramirez-Cheyne J, Lein PJ, Tassone F, Hagerman RJ. {{Increased Severity of Fragile X Spectrum Disorders in the Agricultural Community of Ricaurte, Colombia}}. {International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience}. 2018.
Premutation carriers of the FMR1 gene (CGG repeats between 55 and 200) usually have normal intellectual abilities but approximately 20% are diagnosed with developmental problems or autism spectrum disorder. Additionally, close to 50% have psychiatric problems such as anxiety, ADHD and/or depression. The spectrum of fragile X disorders also includes Fragile-X-associated primary ovarian insufficiency (FXPOI) in female carriers and Fragile-X-associated tremor/ataxia syndrome (FXTAS) in older male and female carriers. We evaluated 25 premutation carriers in the rural community of Ricaurte Colombia and documented all behavioral problems, social deficits and clinical signs of FXPOI and FXTAS as well as reviewed the medical and obstetric history. We found an increased frequency and severity of symptoms of fragile X spectrum disorders, which might be related to the vulnerability of FMR1 premutation carriers to higher exposure to neurotoxic pesticides in this rural community.
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30. Schendel DE, Thorsteinsson E. {{Cumulative Incidence of Autism Into Adulthood for Birth Cohorts in Denmark, 1980-2012}}. {Jama}. 2018; 320(17): 1811-3.
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31. Sethi C, Harrop C, Zhang W, Pritchett J, Whitten A, Boyd BA. {{Parent and professional perspectives on behavioral inflexibility in autism spectrum disorders: A qualitative study}}. {Autism : the international journal of research and practice}. 2018: 1362361318810217.
Restricted and repetitive behaviors are a core feature of autism spectrum disorder; however, research on the functional impact of these behaviors on the quality of life for individuals with autism spectrum disorder and their families remains scarce. We conducted focus groups with parents of children with autism spectrum disorder and clinicians in order to better characterize the functional impact of behavioral inflexibility, which represents one potential dimensional construct that could account for the breadth of behaviors comprising the restricted and repetitive behavior domain. Transcripts of the focus groups were analyzed using qualitative analysis coding methods to determine parent and clinician beliefs on a range of issues related to behavioral inflexibility including overall impact, types of child behaviors, and strategies for managing behavioral inflexibility. Thematic analysis revealed that parents and clinicians view behavioral inflexibility as an important behavior that impacts multiple areas of functioning, relates to other restricted and repetitive behaviors as well as social communication behaviors, and warrants targeted treatment. Notably, many parents and clinicians emphasized some positive consequences of behavioral inflexibility as well. These findings add crucial insights into the functional impact of behavioral inflexibility and restricted and repetitive behaviors as a whole and suggest that behavioral inflexibility represents an important avenue for future research.
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32. Shtayermman O. {{Robert Naseef: Autism in the Family: Caring and Coping Together : Brookes Publishing; 1st Edition, USA 2012, 356 pp, ISBN-13: 978-1598572414, $24.58 (Paper)}}. {Journal of autism and developmental disorders}. 2018.
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33. Shui AM, Katz T, Malow BA, Mazurek MO. {{Predicting sleep problems in children with autism spectrum disorders}}. {Research in developmental disabilities}. 2018; 83: 270-9.
BACKGROUND: Sleep difficulties in children with autism spectrum disorders (ASD) have been well-established. AIMS: To develop a model to predict sleep problems in children with ASD. METHODS AND PROCEDURES: A sample of children in the Autism Speaks-Autism Treatment Network (ATN) registry without parent-reported sleep problems at baseline and with sleep problem (yes/no) data at first annual followup was randomly split into training (n = 527) and test (n = 518) samples. Model predictors were selected using the training sample, and a threshold for classifying children at risk was determined. Comparison of the predicted and true sleep problem status of the test sample yielded model performance measures. OUTCOMES AND RESULTS: In a multivariable model aggressive behavior among children with no sleep problems reported at baseline was associated with having more sleep problems at the first annual follow-up visit. This model performed in the test sample with high sensitivity and accurate prediction of low risk. CONCLUSIONS AND IMPLICATIONS: Among children with ASD aggressive behavior independently predicts sleep problems. The model’s high sensitivity for identifying children at risk and its accurate prediction of low risk can help with treatment and prevention of sleep problems. Further data collection may provide better prediction through methods requiring larger samples.
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34. Strang JF, Janssen A, Tishelman A, Leibowitz SF, Kenworthy L, McGuire JK, Edwards-Leeper L, Mazefsky CA, Rofey D, Bascom J, Caplan R, Gomez-Lobo V, Berg D, Zaks Z, Wallace GL, Wimms H, Pine-Twaddell E, Shumer D, Register-Brown K, Sadikova E, Anthony LG. {{Revisiting the Link: Evidence of the Rates of Autism in Studies of Gender Diverse Individuals}}. {Journal of the American Academy of Child and Adolescent Psychiatry}. 2018; 57(11): 885-7.
Turban and van Schalkwyk assert in their Translations article, « ‘Gender Dysphoria’ and Autism Spectrum Disorder: Is the Link Real? » that an over-representation of autism spectrum disorder (ASD) in gender dysphoria is unsupported based on current evidence. Turban and van Schalkwyk discuss 7 of the currently 19 available empirical studies (excluding reviews and case reports) of the over-occurrence of ASD and/or autism traits with gender dysphoria/diversity. They are correct to note that some ASD screeners may lack specificity; that is, a clinical-range total score could indicate non-ASD-related mental health conditions or other developmental difference. However, they do not account for the 7 available studies which specifically report rates of clinical diagnoses of ASD among unselected gender-diverse samples. We suggest also that many of the studies that assess ASD-symptoms in gender-diverse groups are more convincing than suggested by Turban and van Schalkwyk because they employ measures assessing the multi-dimensionality of ASD symptoms and report significant elevations not only for socially-related symptoms but also for the various components of restricted and repetitive behaviors and interests (RRBI) core to ASD. We come together to write this response as gender clinicians and researchers, autism clinicians and researchers, and key stakeholders, including autistic and autistic transgender self-advocates. We work and live with the co-occurrence of autism and gender diversity on a daily basis, and we are concerned that perpetuating misunderstanding about the co-occurrence places individuals at risk.
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35. Tinkov AA, Skalnaya MG, Simashkova NV, Klyushnik TP, Skalnaya AA, Bjorklund G, Notova SV, Kiyaeva EV, Skalny AV. {{Association between catatonia and levels of hair and serum trace elements and minerals in autism spectrum disorder}}. {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie}. 2018; 109: 174-80.
The objective of the study was to investigate the association between catatonia in autism spectrum disorder (ASD) and the levels of hair and serum trace elements and minerals in children with ASD. The levels of hair and serum trace elements and minerals of boys suffering from ASD with (n = 30) and without (n = 30) catatonia, as well as 30 age- and sex-matched neurotypical controls were assessed using ICP-MS. Hair calcium (Ca) and selenium (Se) levels were lower in ASD patients as compared to the controls. Hair mercury (Hg) levels in ASD patients were more than 3-fold and 2-fold higher as compared to the controls and children with catatonia in ASD. Hair iodine (I) and manganese (Mn) were the lowest and the highest in ASD + Catatonia, respectively. Serum aluminium (Al) and cadmium (Cd) levels in healthy controls were significantly higher in comparison to the patients of both groups. Serum chromium (Cr), copper (Cu) levels were significantly increased in patients with ASD and catatonia, whereas vanadium (V) levels were elevated in patients both with and without catatonia. Multiple regression analysis demonstrated that hair Hg and serum Al and Cd levels were negatively associated with catatonia in ASD in crude and adjusted models. Although the etiology of catatonia in ASD is unclear, the obtained data demonstrate that catatonic symptoms in ASD may be at least partially mediated by altered trace element levels. Further studies are required to elucidate the role of trace elements in the potential signaling mechanisms of catatonia.
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36. Trevisan DA, Hoskyn M, Birmingham E. {{Facial Expression Production in Autism: A Meta-Analysis}}. {Autism research : official journal of the International Society for Autism Research}. 2018.
This meta-analysis summarized studies that examined group differences on the production of facial expressions in participants with ASD compared to typically developing or nonautistic clinical comparison groups. The overall summary effect from 67 effect sizes representing the average ASD-comparison group differences in facial expressions was -0.481, indicating a moderate effect size. We conducted subgroup analyses to group effect sizes according to separate facial expression abilities identified in the literature. These analyses revealed that participants with ASD display facial expressions less frequently and for less amount of time, and they are less likely to share facial expressions with others or automatically mimic the expressions of real faces or face stimuli. Their facial expressions are also judged to be lower in quality and are expressed less accurately. However, participants with ASD do not express emotions less intensely, nor is their reaction time of expression onset slower in response to odors, startling sensations, or in response to face stimuli in mimicry studies. ASD-comparison group differences were moderated by matching procedures, age, and intellectual functioning of the ASD participants suggesting that persons with higher IQ and larger number of accumulated life experiences are better able to produce facial expressions that are more consistent with « neurotypical » norms. Group differences were also stronger for « covertly elicited » than « explicitly elicited » facial expressions suggesting individuals with ASD may naturally produce facial expressions differently from other populations, but are less impaired in expressing emotions typically when prompted to do so in a laboratory setting. Autism Research 2018. (c) 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: We reviewed studies that compared facial expressions in people with and without autism. Results revealed that facial expressions of people with autism are atypical in appearance and quality and are used atypically to regulate social interactions. The magnitude of these differences was influenced by participant characteristics (e.g. age and intellectual functioning), and by how facial expressions were measured and analyzed in various studies.
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37. van der Miesen AIR, Cohen-Kettenis PT, de Vries ALC. {{Is There a Link Between Gender Dysphoria and Autism Spectrum Disorder?}}. {Journal of the American Academy of Child and Adolescent Psychiatry}. 2018; 57(11): 884-5.
In their Translations article in the January issue of the Journal, Turban and van Schalkwyk provide a critical evaluation of the recently published literature on co-occurring gender dysphoria (GD) and autism spectrum disorder (ASD).(1) In addition, they refer to this flux in interest as part of a larger increase in publications on transgender people, which are mostly reviews and do not contain new data. Given the low-grade evidence in this field for most clinical recommendations,(2) good-quality research is of great relevance. We support the debate on the GD-ASD literature and acknowledge that translations of the findings to the lay press such as « Do transgender children just have autism? » are not helpful. Also, we agree with many of the limitations brought forward by the authors and acknowledge that, at present, sound underlying evidence for a GD-ASD link is lacking. However, we believe that some nuance in argumentation could help forward the debate of this clinically important topic.
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38. Venker CE, Edwards J, Saffran JR, Ellis Weismer S. {{Thinking Ahead: Incremental Language Processing is Associated with Receptive Language Abilities in Preschoolers with Autism Spectrum Disorder}}. {Journal of autism and developmental disorders}. 2018.
In typical development, listeners can use semantic content of verbs to facilitate incremental language processing-a skill that is associated with existing language skills. Studies of children with ASD have not identified an association between incremental language processing in semantically-constraining contexts and language skills, perhaps because participants were adolescents and/or children with strong language skills. This study examined incremental language processing and receptive language in young children with ASD with a range of language skills. Children showed a head start when presented with semantically-constraining verbs (e.g., Read the book) compared to neutral verbs (e.g., Find the book). Children with weaker receptive language showed a smaller head start than children with stronger receptive language skills, suggesting continuity between typical development and ASD.
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39. Vettori S, Jacques C, Boets B, Rossion B. {{Can the N170 Be Used as an Electrophysiological Biomarker Indexing Face Processing Difficulties in Autism Spectrum Disorder?}}. {Biological psychiatry Cognitive neuroscience and neuroimaging}. 2018.
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40. Wang M, Zhou J, He F, Cai C, Wang H, Wang Y, Lin Y, Rong H, Cheng G, Xu R, Zhou W. {{Alteration of gut microbiota-associated epitopes in children with autism spectrum disorders}}. {Brain, behavior, and immunity}. 2018.
BACKGROUND: Autism spectrum disorder (ASD) affects 1% of children and has no cure. Gastrointestinal (GI) problems are common in children with ASD, and although gut microbiota is known to play an important role in ASD through the gut-brain axis, the specific mechanism is unknown. Recent evidence suggests that gut microbiota may participate in the pathogenesis of ASD through immune- and inflammation-mediated pathways. Here, we identified potentially immunogenic epitopes derived from gut microbiota in stool samples from ASD children with and without GI problems and typically developing (TD) children. METHODS: Candidate gut microbiota-associated epitopes (MEs) were identified by blast shotgun metagenomic sequencing of fecal samples from 43 ASD children (19 with and 24 without GI involvement) and 31 sex- and age-matched typically developing (TD) children. Potentially immunogenic epitopes were screened against a predictive human Immune Epitope Database. The composition and abundance of candidate MEs were compared between the three groups of children. RESULTS: MEs identified in ASD children with GI problems were significantly more diverse than those in TD children. ME composition could discriminate between the three groups of children. We identified 34 MEs that were significantly more or less abundant in ASD children than TD children, most (29/34) of the differences in MEs were reduced in ASD and associated with abnormal gut IgA level and altered gut microbiota composition, these MEs were limited effected by clinical factors such as age, gender, and GI problems, of which eleven MEs were pathogenic microorganisms peptides with strong T or B cell response, nine MEs showed high homology to peptides from human self proteins associated with autoimmune disease occurrence, eliciting immune attack against hematopoietic stem cells and inhibition antigen binding. We also found that the abundance of five MEs were increased in ASD, including three human self proteins, gap junction alpha-1 (GJA1), paired box protein Pax-3 (PAX3) and eyes absent homolog 1 isoform 4 (EYA1) which associated with cancer, and a ME with homology to a Listeriolysin O peptide from the pathogenic bacterium Listeria monocytogenes was significantly increased in ASD children compared with TD children. CONCLUSIONS: Our findings demonstrate the abnormal of MEs composition in the gut of children with ASD, moreover, the abnormality in MEs composition was associated with abnormal gut IgA levels and altered gut microbiota composition, this abnormality also suggests that there may be abnormalities in intestinal immunity in children with ASD; In all, thirty-four MEs identified were potential biomarker of ASD, andalterations in MEs may contribute to abnormalities in gut immunity and/or homeostasis in ASD children. Further study of the MEs identified here may advance our understanding of the pathogenesis of ASD.
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41. Williams TV, Hartmann K, Paulson JF, Raffaele CT, Urbano MR. {{Life After an Autism Spectrum Disorder Diagnosis: A Comparison of Stress and Coping Profiles of African American and Euro-American Caregivers}}. {Journal of autism and developmental disorders}. 2018.
The purpose of the present study was to understand how caregiver stress and coping behaviors impact African American and Euro-American families differently when caring for a child with autism. This study used discriminate function analysis to contrast the stress and coping profiles of Euro-American caregivers who are more acculturated with the majority culture with African American caregivers who ascribe to more traditional values. A sample of 103 families was recruited (52 Euro-American, 51 African American). African American families reported significantly more stress and utilizing more varied coping strategies than their Euro-American counterparts. Additional differences were found between the high and low acculturated African American groups such that low acculturated African Americans were more likely to engage in religious coping.
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42. Withane N, Dhossche DM. {{Electroconvulsive Treatment for Catatonia in Autism Spectrum Disorders}}. {Child and adolescent psychiatric clinics of North America}. 2019; 28(1): 101-10.
Catatonia has been increasingly recognized in people with autism spectrum disorders (ASD). Assessment, diagnosis, and treatments are reviewed and illustrated with 2 new case vignettes. The use of electroconvulsive treatment (ECT) is recommended in patients who fail to respond to medical treatments, including a trial of lorazepam or another benzodiazepine. The importance of maintenance ECT is discussed. There is an urgent need for prospective studies of catatonia in ASD and for controlled treatment trials.
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43. Wu J, Yu P, Jin X, Xu X, Li J, Li Z, Wang M, Wang T, Wu X, Jiang Y, Cai W, Mei J, Min Q, Xu Q, Zhou B, Guo H, Wang P, Zhou W, Hu Z, Li Y, Cai T, Wang Y, Xia K, Jiang YH, Sun ZS. {{Genomic landscapes of Chinese sporadic autism spectrum disorders revealed by whole-genome sequencing}}. {Journal of genetics and genomics = Yi chuan xue bao}. 2018.
Autism spectrum disorder (ASD) is a neurodevelopmental disorder with considerable clinical and genetic heterogeneity. In this study, we identified all classes of genomic variants from whole-genome sequencing (WGS) dataset of 32 Chinese trios with ASD, including de novo mutations, inherited variants, copy number variants (CNVs) and genomic structural variants. A higher mutation rate (Poisson test, P<2.2x10(-16)) in exonic (1.37x10(-8)) and 3'-UTR regions (1.42x10(-8)) was revealed in comparison with that of whole genome (1.05x10(-8)). Using an integrated model, we identified 87 potentially risk genes (P<0.01) from 4832 genes harboring various rare deleterious variants, including CHD8 and NRXN2, implying that the disorders may be in favor to multiple-hit. In particular, frequent rare inherited mutations of several microcephaly-associated genes (ASPM, WDR62, and ZNF335) were found in ASD. In chromosomal structure analyses, we found four de novo CNVs and one de novo chromosomal rearrangement event, including a de novo duplication of UBE3A-containing region at 15q11.2-q13.1, which causes Angelman syndrome and microcephaly, and a disrupted TNR due to de novo chromosomal translocation t(1; 5)(q25.1; q33.2). Taken together, our results suggest that abnormalities of centrosomal function and chromatin remodeling of the microcephaly-associated genes may be implicated in pathogenesis of ASD. Adoption of WGS as a new yet efficient technique to illustrate the full genetic spectrum in complex disorders, such as ASD, could provide novel insights into pathogenesis, diagnosis and treatment. Lien vers le texte intégral (Open Access ou abonnement)
44. Zhou P, Zhan L, Ma H. {{Predictive Language Processing in Preschool Children with Autism Spectrum Disorder: An Eye-Tracking Study}}. {Journal of psycholinguistic research}. 2018.
Sentence comprehension relies on the abilities to rapidly integrate different types of linguistic and non-linguistic information. The present study investigated whether Mandarin-speaking preschool children with autism spectrum disorder (ASD) are able to use verb information predictively to anticipate the upcoming linguistic input during real-time sentence comprehension. 26 five-year-olds with ASD, 25 typically developing (TD) five-year-olds and 24 TD four-year-olds were tested using the visual world eye-tracking paradigm. The results showed that the 5-year-olds with ASD, like their TD peers, exhibited verb-based anticipatory eye movements during real-time sentence comprehension. No difference was observed between the ASD and TD groups in the time course of their eye gaze patterns, indicating that Mandarin-speaking preschool children with ASD are able to use verb information as effectively and rapidly as TD peers to predict the upcoming linguistic input.
