1. Biran J, Levkowitz G. {{Zebrafish Reel in Phenotypic Suppressors of Autism}}. {Neuron};2016 (Feb 17);89(4):673-675.
Chemical genetics can help decipher novel pathways underlying neurodevelopmental psychiatric impairments. Hoffman et al. (2016) utilized behavioral profiling of psychoactive compounds in zebrafish and identified estrogens as suppressors of a phenotype resulting from loss of an autism risk gene.
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2. Chown N, Hughes L. {{History and First Descriptions of Autism: Asperger Versus Kanner Revisited}}. {J Autism Dev Disord};2016 (Feb 17)
When reading Michael Fitzgerald’s chapter entitled ‘Autism: Asperger’s Syndrome-History and First Descriptions’ in ‘Asperger’s Disorder’ edited by Rausch, Johnson and Casanova, a while ago, one of us was struck by his contention that Kanner was guilty of plagiarism as well as non-attribution of Asperger’s 1938 paper ‘Das psychisch abnorme kind’ (Fitzgerald in Asperger’s disorder. Informa Healthcare, New York, 2008) published in a Vienna weekly. Steve Silberman has discovered evidence that Kanner rescued Asperger’s chief diagnostician from the Nazis in 1944 so must have been aware of Asperger’s work and conclusions. Fitzgerald was on the right track but it appears that Kanner may have plagiarised Asperger’s ideas rather than his 1938 paper.
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3. Dolan BK, Van Hecke AV, Carson AM, Karst JS, Stevens S, Schohl KA, Potts S, Kahne J, Linneman N, Remmel R, Hummel E. {{Brief Report: Assessment of Intervention Effects on In Vivo Peer Interactions in Adolescents with Autism Spectrum Disorder (ASD)}}. {J Autism Dev Disord};2016 (Feb 17)
This study aimed to evaluate the effectiveness of a randomized controlled trial of a social skills intervention, the Program for the Education and Enrichment of Relational Skills (PEERS: Laugeson et al. in J Autism Dev Disord 39(4): 596-606, 2009), by coding digitally recorded social interactions between adolescent participants with ASD and a typically developing adolescent confederate. Adolescent participants engaged in a 10-min peer interaction at pre- and post-treatment. Interactions were coded using the Contextual Assessment of Social Skills (Ratto et al. in J Autism Dev Disord 41(9): 1277-1286, 2010). Participants who completed PEERS demonstrated significantly improved vocal expressiveness, as well as a trend toward improved overall quality of rapport, whereas participants in the waitlist group exhibited worse performance on these domains. The degree of this change was related to knowledge gained in PEERS.
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4. Gokcen E, Frederickson N, Petrides KV. {{Theory of Mind and Executive Control Deficits in Typically Developing Adults and Adolescents with High Levels of Autism Traits}}. {J Autism Dev Disord};2016 (Feb 17)
Autism spectrum disorder (ASD) is characterised by profound difficulties in empathic processing and executive control. Whilst the links between these processes have been frequently investigated in populations with autism, few studies have examined them at the subclinical level. In addition, the contribution of alexithymia, a trait characterised by impaired interoceptive awareness and empathy, and elevated in those with ASD, is currently unclear. The present two-part study employed a comprehensive battery of tasks to examine these processes. Findings support the notion that executive function and theory of mind are related abilities. They also suggest that individuals with elevated levels of autism-like traits experience a partially similar pattern of social and executive function difficulties to those diagnosed with ASD, and that these impairments are not explained by co-occurring alexithymia.
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5. Granich J, Lin A, Hunt A, Wray J, Dass A, Whitehouse AJ. {{Obesity and associated factors in youth with an autism spectrum disorder}}. {Autism};2016 (Feb 17)
Weight status on children and youth with autism spectrum disorder is limited. We examined the prevalence of overweight/obesity in children and youth with autism spectrum disorder, and associations between weight status and range of factors. Children and youth with autism spectrum disorder aged 2-16 years (n = 208) and their parents participated in this study. Body mass index was calculated using the Centers for Disease Control and Prevention growth charts and the International Obesity Task Force body mass index cut-offs. The Autism Diagnostic Observation Schedule was administered. Parents completed questionnaires about socio-demographics, diagnosed comorbidities, sleep disturbances, social functioning and medication of youth with autism spectrum disorder. The prevalence of overweight/obesity in participants with autism spectrum disorder was 35%. One quarter of obese children and youth (25.6%) had obese parents. There was a significant association between children and youth’s body mass index and maternal body mass index (r = 0.25, n = 199, p < 0.001). The gender and age, parental education, family income, ethnicity, autism spectrum disorder severity, social functioning, psychotropic and complementary medication use of children and youth with autism spectrum disorder were not statistically associated with their weight status. Findings suggest the need for clinical settings to monitor weight status of children and youth with autism spectrum disorder in a bid to manage or prevent overweight/obesity in this population. Incorporating a family system approach to influence health behaviours among children and youth with autism spectrum disorder especially for specific weight interventions is warranted and should be further explored.
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6. Guo W, Molinaro G, Collins KA, Hays SA, Paylor R, Worley PF, Szumlinski KK, Huber KM. {{Selective Disruption of Metabotropic Glutamate Receptor 5-Homer Interactions Mimics Phenotypes of Fragile X Syndrome in Mice}}. {J Neurosci};2016 (Feb 17);36(7):2131-2147.
Altered function of the Gq-coupled, Group 1 metabotropic glutamate receptors, specifically mGlu5, is implicated in multiple mouse models of autism and intellectual disability. mGlu5 dysfunction has been most well characterized in the fragile X syndrome mouse model, the Fmr1 knock-out (KO) mouse, where pharmacological and genetic reduction of mGlu5 reverses many phenotypes. mGlu5 is less associated with its scaffolding protein Homer in Fmr1 KO mice, and restoration of mGlu5-Homer interactions by genetic deletion of a short, dominant negative of Homer, H1a, rescues many phenotypes of Fmr1 KO mice. These results suggested that disruption of mGlu5-Homer leads to phenotypes of FXS. To test this idea, we examined mice with a knockin mutation of mGlu5 (F1128R; mGlu5(R/R)) that abrogates binding to Homer. Although FMRP levels were normal, mGlu5(R/R) mice mimicked multiple phenotypes of Fmr1 KO mice, including reduced mGlu5 association with the postsynaptic density, enhanced constitutive mGlu5 signaling to protein synthesis, deficits in agonist-induced translational control, protein synthesis-independent LTD, neocortical hyperexcitability, audiogenic seizures, and altered behaviors, including anxiety and sensorimotor gating. These results reveal new roles for the Homer scaffolds in regulation of mGlu5 function and implicate a specific molecular mechanism in a complex brain disease. SIGNIFICANCE STATEMENT: Abnormal function of the metabotropic, or Gq-coupled, glutamate receptor 5 (mGlu5) has been implicated in neurodevelopmental disorders, including a genetic cause of intellectual disability and autism called fragile X syndrome. In brains of a mouse model of fragile X, mGlu5 is less associated with its binding partner Homer, a scaffolding protein that regulates mGlu5 localization to synapses and its ability to activate biochemical signaling pathways. Here we show that a mouse expressing a mutant mGlu5 that cannot bind to Homer is sufficient to mimic many of the biochemical, neurophysiological, and behavioral symptoms observed in the fragile X mouse. This work provides strong evidence that Homer-mGlu5 binding contributes to symptoms associated with neurodevelopmental disorders.
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7. Hoffman EJ, Turner KJ, Fernandez JM, Cifuentes D, Ghosh M, Ijaz S, Jain RA, Kubo F, Bill BR, Baier H, Granato M, Barresi MJ, Wilson SW, Rihel J, State MW, Giraldez AJ. {{Estrogens Suppress a Behavioral Phenotype in Zebrafish Mutants of the Autism Risk Gene, CNTNAP2}}. {Neuron};2016 (Feb 17);89(4):725-733.
Autism spectrum disorders (ASDs) are a group of devastating neurodevelopmental syndromes that affect up to 1 in 68 children. Despite advances in the identification of ASD risk genes, the mechanisms underlying ASDs remain unknown. Homozygous loss-of-function mutations in Contactin Associated Protein-like 2 (CNTNAP2) are strongly linked to ASDs. Here we investigate the function of Cntnap2 and undertake pharmacological screens to identify phenotypic suppressors. We find that zebrafish cntnap2 mutants display GABAergic deficits, particularly in the forebrain, and sensitivity to drug-induced seizures. High-throughput behavioral profiling identifies nighttime hyperactivity in cntnap2 mutants, while pharmacological testing reveals dysregulation of GABAergic and glutamatergic systems. Finally, we find that estrogen receptor agonists elicit a behavioral fingerprint anti-correlative to that of cntnap2 mutants and show that the phytoestrogen biochanin A specifically reverses the mutant behavioral phenotype. These results identify estrogenic compounds as phenotypic suppressors and illuminate novel pharmacological pathways with relevance to autism.
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8. Krakovich TM, McGrew JH, Yu Y, Ruble LA. {{Stress in Parents of Children with Autism Spectrum Disorder: An Exploration of Demands and Resources}}. {J Autism Dev Disord};2016 (Feb 17)
We applied the ABCX model of stress and coping to assess the association between child and family demands, school-based resources (i.e., parent-teacher alliance and COMPASS, a consultation intervention), and two measures of parent stress: perceptions of the demands of raising a child (Child domain) and reactions to those demands (Parent domain). Data were analyzed from seventy-nine parents of children ages 3-9 with ASD participating in two randomized controlled trials of COMPASS. Stronger parent-teacher alliance correlated with decreased Parent domain stress and participation in COMPASS correlated with decreased Child domain stress after controlling for baseline stress. The study indicates that school-based resources can help reduce parent stress.
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9. Kung KT, Constantinescu M, Browne WV, Noorderhaven RM, Hines M. {{No relationship between early postnatal testosterone concentrations and autistic traits in 18 to 30-month-old children}}. {Mol Autism};2016;7:15.
BACKGROUND: Some previous research has suggested that testosterone prenatally contributes to gender differences in autistic traits, but little is known about the role of testosterone during early postnatal development (mini-puberty). Two prior studies found no sex difference in testosterone postnatally in saliva samples and detected little to no relationship between testosterone postnatally and autistic traits in toddlers. These findings may reflect late measurements of testosterone at 3 to 4 months of age, after the peak of mini-puberty at 1 to 3 months of age. The present study examined the relationship between testosterone at 1 to 3 months of age and autistic traits at 18 to 30 months of age. FINDINGS: Testosterone was measured in saliva samples collected from children at 1 to 3 months of age. When the children (40 boys, 47 girls) reached 18 to 30 months of age, parents completed the Quantitative Checklist for Autism in Toddlers (Q-CHAT). Boys had higher concentrations of testosterone postnatally and higher Q-CHAT scores than girls. However, testosterone did not correlate with Q-CHAT scores in boys, girls, or the entire sample. CONCLUSIONS: The current results suggest that testosterone during the early postnatal period does not contribute to later autistic traits. Given our relatively small samples and therefore limited power, however, further research could usefully examine if testosterone in saliva samples collected during the peak of mini-puberty in larger groups predicts autistic traits or other traits that show gender differences.
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10. Mei Y, Monteiro P, Zhou Y, Kim JA, Gao X, Fu Z, Feng G. {{Adult restoration of Shank3 expression rescues selective autistic-like phenotypes}}. {Nature};2016 (Feb 17)
Because autism spectrum disorders are neurodevelopmental disorders and patients typically display symptoms before the age of three, one of the key questions in autism research is whether the pathology is reversible in adults. Here we investigate the developmental requirement of Shank3 in mice, a prominent monogenic autism gene that is estimated to contribute to approximately 1% of all autism spectrum disorder cases. SHANK3 is a postsynaptic scaffold protein that regulates synaptic development, function and plasticity by orchestrating the assembly of postsynaptic density macromolecular signalling complex. Disruptions of the Shank3 gene in mouse models have resulted in synaptic defects and autistic-like behaviours including anxiety, social interaction deficits, and repetitive behaviour. We generated a novel Shank3 conditional knock-in mouse model, and show that re-expression of the Shank3 gene in adult mice led to improvements in synaptic protein composition, spine density and neural function in the striatum. We also provide behavioural evidence that certain behavioural abnormalities including social interaction deficit and repetitive grooming behaviour could be rescued, while anxiety and motor coordination deficit could not be recovered in adulthood. Together, these results reveal the profound effect of post-developmental activation of Shank3 expression on neural function, and demonstrate a certain degree of continued plasticity in the adult diseased brain.
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11. Rodgers J, Wigham S, McConachie H, Freeston M, Honey E, Parr JR. {{Development of the anxiety scale for children with autism spectrum disorder (ASC-ASD)}}. {Autism Res};2016 (Feb 17)
Many children with autism spectrum disorder (ASD) experience high levels of anxiety. A widely used measure for typically developing children is the Revised Child Anxiety and Depression Scale (RCADS). However, such anxiety measures may require adaptation to accommodate characteristics of those with ASD. An adapted version of the RCADS was created based on empirical evidence of anxiety phenomenology in ASD, which included additional items related to sensory anxiety, intolerance of uncertainty, and phobias. Content validity was refined during focus groups with parents. Polychoric factor analysis was undertaken on data from 170 children with ASD, aged 8-16, and their parents. This process resulted in the creation of a new 24 item scale (self and parent report) each with four subscales: Performance Anxiety, Uncertainty, Anxious Arousal, and Separation Anxiety, with evidence of good reliability and validity. The freely available Anxiety Scale for Children – ASD, Parent and Child versions (ASC-ASD) has promising psychometric properties including good internal consistency, validity, and 1 month test-retest reliability. Autism Res 2016. & 2016 International Society for Autism Research, Wiley Periodicals, Inc.
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12. Roth BM, Kralovic S, Roizen NJ, Spannagel SC, Minich N, Knapp J. {{Impact of Autism Navigator on Access to Services}}. {J Dev Behav Pediatr};2016 (Feb 17)
OBJECTIVE: To determine whether access to an Autism Patient Navigator (APN) for children diagnosed with autism spectrum disorder (ASD) at <48 months of age would be useful and lead to more appointments with needed services. METHOD: Participants included parents of 39 children diagnosed with ASD in a multidisciplinary clinic. After diagnosis, the patients were randomized to 4 groups: Medicaid early (n = 9) or late support (n = 9) and non-Medicaid early (n = 11) or late support (n = 10). Early access to the APN was at the family meeting and later at 3 months after diagnosis. Data included demographic information and completion by phone interview at 3 months postdiagnosis of a questionnaire on the usefulness of the assessment and parent's desire or ability to obtain recommended services. RESULTS: Demographically, the groups were not different. Children were most frequently male, white, non-Hispanic, and non-Medicaid with a mean age of 35 months. In comparison with the non-Medicaid groups, the Medicaid groups more often endorsed the 9 questions on the usefulness of the assessment as being "A Great Deal" useful (p = .022). Groups with early support were more successful in scheduling or completing appointments for recommended services overall including medical, educational, therapeutic, and parent resource appointments (p = .031). Barriers to services or resources were reported by 35.9%. CONCLUSION: Parents of young children with Medicaid with a recent diagnosis of ASD found the assessment "very useful" compared with non-Medicaid group. The groups with immediate access to an APN were more successful with scheduling and completing appointments.
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13. Sharda M, Foster NE, Tryfon A, Doyle-Thomas KA, Ouimet T, Anagnostou E, Evans AC, Zwaigenbaum L, Lerch JP, Lewis JD, Hyde KL. {{Language Ability Predicts Cortical Structure and Covariance in Boys with Autism Spectrum Disorder}}. {Cereb Cortex};2016 (Feb 17)
There is significant clinical heterogeneity in language and communication abilities of individuals with Autism Spectrum Disorders (ASD). However, no consistent pathology regarding the relationship of these abilities to brain structure has emerged. Recent developments in anatomical correlation-based approaches to map structural covariance networks (SCNs), combined with detailed behavioral characterization, offer an alternative for studying these relationships. In this study, such an approach was used to study the integrity of SCNs of cortical thickness and surface area associated with language and communication, in 46 high-functioning, school-age children with ASD compared with 50 matched, typically developing controls (all males) with IQ > 75. Findings showed that there was alteration of cortical structure and disruption of fronto-temporal cortical covariance in ASD compared with controls. Furthermore, in an analysis of a subset of ASD participants, alterations in both cortical structure and covariance were modulated by structural language ability of the participants, but not communicative function. These findings indicate that structural language abilities are related to altered fronto-temporal cortical covariance in ASD, much more than symptom severity or cognitive ability. They also support the importance of better characterizing ASD samples while studying brain structure and for better understanding individual differences in language and communication abilities in ASD.
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14. Wang Y, Billon C, Walker JK, Burris TP. {{Therapeutic Effect of a Synthetic RORalpha/gamma Agonist in an Animal Model of Autism}}. {ACS Chem Neurosci};2016 (Feb 17);7(2):143-148.
Autism is a developmental disorder of the nervous system associated with impaired social communication and interactions as well excessive repetitive behaviors. There are no drug therapies that directly target the pathology of this disease. The retinoic acid receptor-related orphan receptor alpha (RORalpha) is a nuclear receptor that has been demonstrated to have reduced expression in many individuals with autism spectrum disorder (ASD). Several genes that have been shown to be downregulated in individuals with ASD have also been identified as putative RORalpha target genes. Utilizing a synthetic RORalpha/gamma agonist, SR1078, that we identified previously, we demonstrate that treatment of BTBR mice (a model of autism) with SR1078 results in reduced repetitive behavior. Furthermore, these mice display increased expression of ASD-associated RORalpha target genes in both the brains of the BTBR mice and in a human neuroblastoma cell line treated with SR1078. These data suggest that pharmacological activation of RORalpha may be a method for treatment of autism.
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15. Webb SJ, Neuhaus E, Faja S. {{Face Perception and Learning in Autism Spectrum Disorders}}. {Q J Exp Psychol (Hove)};2016 (Feb 17):1-44.
Autism Spectrum Disorder (ASD) is characterized by impairment in social communication and restricted and repetitive interests (American Psychiatric Association, 2013). While not included in the diagnostic characterization, aspects of face processing and learning have shown disruptions at all stages of development in ASD, although the exact nature and extent of the impairment varies by age and level of functioning of the ASD sample as well as by task demands. In this review, we examine the nature of face attention, perception, and learning in individuals with ASD focusing on 3 broad age ranges (early development, middle childhood, and adolescence/adulthood). We propose that early delays in basic face processing contribute to the atypical trajectory of social communicative skills in individuals with ASD and contribute to poor social learning throughout development. Face learning is a life-long necessity, as the social world of individual only broadens with age, and thus addressing both the source of the impairment in ASD as well as the trajectory of ability throughout the lifespan, through targeted treatments, may serve to positively impact the lives of individuals who struggle with social understanding and information.
