1. Codagnone MG, Podesta MF, Uccelli NA, Reines A. {{Differential Local Connectivity and Neuroinflammation Profiles in the Medial Prefrontal Cortex and Hippocampus in the Valproic Acid Rat Model of Autism}}. {Dev Neurosci}. 2015; 37(3): 215-31.
Autism spectrum disorders (ASD) are a group of developmental disabilities characterized by impaired social interaction, communication deficit and repetitive and stereotyped behaviors. Neuroinflammation and synaptic alterations in several brain areas have been suggested to contribute to the physiopathology of ASD. Although the limbic system plays an important role in the functions found impaired in ASD, reports on these areas are scarce and results controversial. In the present study we searched in the medial prefrontal cortex (mPFC) and hippocampus of rats exposed to the valproic acid (VPA) model of ASD for early structural and molecular changes, coincident in time with the behavioral alterations. After confirming delayed growth and maturation in VPA rats, we were able to detect decreased exploratory activity and social interaction at an early time point (postnatal day 35). In mPFC, although typical cortical column organization was preserved in VPA animals, we found that interneuronal space was wider than in controls. Hippocampal CA3 (cornu ammonis 3) pyramidal layer and the granular layer of the dentate gyrus both showed a disorganized spatial arrangement in VPA animals. Neuronal alterations were accompanied with increased tomato lectin and glial fibrillary acidic protein (GFAP) immunostainings both in the mPFC and hippocampus. In the latter region, the increased GFAP immunoreactivity was CA3 specific. At the synaptic level, while mPFC from VPA animals showed increased synaptophysin (SYN) immunostaining, a SYN deficit was found in all hippocampal subfields. Additionally, both the mPFC and the hippocampus of VPA rats showed increased neuronal cell adhesion molecule (NCAM) immunostaining together with decreased levels of its polysialylated form (PSA-NCAM). Interestingly, these changes were more robust in the CA3 hippocampal subfield. Our results indicate that exploratory and social deficits correlate with region-dependent neuronal disorganization and reactive gliosis in the mPFC and hippocampus of VPA rats. While microgliosis is spread in these two limbic areas, astrogliosis, although extended in the mPFC, is circumscribed to the CA3 hippocampal subfield. Our work indicates that neuroinflammation and synaptic alterations do coexist in VPA rats, making this model suitable for studying novel aspects of neuron-glia interactions. Moreover, it suggests that the mPFC and hippocampus might behave differently in the context of the local hyperconnectivity and synaptic hypotheses of autism.
2. Germain B, Eppinger MA, Mostofsky SH, DiCicco-Bloom E, Maria BL. {{Recent Advances in Understanding and Managing Autism Spectrum Disorders}}. {J Child Neurol}. 2015.
Autism spectrum disorder in children is a group of neurodevelopmental disorders characterized by difficulties with social communication and behavior. Growing scientific evidence in addition to clinical practice has led the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) to categorize several disorders into the broader category of autism spectrum disorder. As more is learned about how autism spectrum disorder manifests, progress has been made toward better clinical management including earlier diagnosis, care, and when specific interventions are required. The 2014 Neurobiology of Disease in Children symposium, held in conjunction with the 43rd annual meeting of the Child Neurology Society, aimed to (1) describe the clinical concerns involving diagnosis and treatment, (2) review the current status of understanding in the pathogenesis of autism spectrum disorder, (3) discuss clinical management and therapies for autism spectrum disorder, and (4) define future directions of research. The article summarizes the presentations and includes an edited transcript of question-and-answer sessions.
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3. Gong X, Wang H. {{SHANK1 and autism spectrum disorders}}. {Sci China Life Sci}. 2015.
Autism spectrum disorders (ASD) are highly heterogeneous pediatric developmental disorders with estimated heritability more than 70%. Although the genetic factors in ASD are mainly unknown, a large number of gene mutations have been found, especially in genes involved in neurogenesis. The Neurexin-Neuroligin-Shank (NRXN-NLGN-SHANK) pathway plays a key role in the formation, maturation and maintenance of synapses, consistent with the hypothesis of neurodevelopmental abnormality in ASD. Presynaptic NRXNs interact with postsynaptic NLGNs in excitatory glutamatergic synapses. SHANK proteins function as core components of the postsynaptic density (PSD) by interacting with multiple proteins. Recently, deletions and point mutations of the SHANK1 gene have been detected in ASD individuals, indicating the involvement of SHANK1 in ASD. This review focuses on the function of SHANK1 protein, Shank1 mouse models, and the molecular genetics of the SHANK1 gene in human ASD.
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4. Gong Y, Du Y, Li H, Zhang X, An Y, Wu B. {{Parenting stress and affective symptoms in parents of autistic children}}. {Sci China Life Sci}. 2015.
We examined parenting stress and mental health status in parents of autistic children and assessed factors associated with such stress. Participants were parents of 188 autistic children diagnosed with DSM-IV criteria and parents of 144 normally developing children. Parents of autistic children reported higher levels of stress, depression, and anxiety than parents of normally developing children. Mothers of autistic children had a higher risk of depression and anxiety than that did parents of normally developing children. Mothers compared to fathers of autistic children were more vulnerable to depression. Age, behavior problems of autistic children, and mothers’ anxiety were significantly associated with parenting stress.
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5. Hua R, Wei M, Zhang C. {{The complex genetics in autism spectrum disorders}}. {Sci China Life Sci}. 2015.
Autism spectrum disorders (ASD) are a pervasive neurodevelopmental disease characterized by deficits in social interaction and nonverbal communication, as well as restricted interests and stereotypical behavior. Genetic changes/heritability is one of the major contributing factors, and hundreds to thousands of causative and susceptible genes, copy number variants (CNVs), linkage regions, and microRNAs have been associated with ASD which clearly indicates that ASD is a complex genetic disorder. Here, we will briefly summarize some of the high-confidence genetic changes in ASD and their possible roles in their pathogenesis.
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6. Kreiser NL, White SW. {{ASD Traits and Co-occurring Psychopathology: The Moderating Role of Gender}}. {J Autism Dev Disord}. 2015.
The higher prevalence of autism spectrum disorder (ASD) in males, relative to that seen in females, is a well-replicated phenomenon. A growing body of research has suggested that there may be gender differences in core ASD deficits and patterns of psychiatric comorbidity among adolescents and adults with ASD. The present study sought to determine if association between psychiatric diagnoses and ASD traits differed by gender in a young adult analogue sample. Participants (n = 84) were university students, scoring either above or below a pre-determined cut-off of ASD traits. Using a structured psychiatric screening interview, ASD traits were found to more strongly predict exceeding screening threshold for mood disorders in females than in males. Future directions and clinical implications are discussed.
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7. LeBlanc JJ, DeGregorio G, Centofante E, Vogel-Farley VK, Barnes K, Kaufmann WE, Fagiolini M, Nelson CA. {{Visual evoked potentials detect cortical processing deficits in Rett syndrome}}. {Ann Neurol}. 2015.
OBJECTIVE: Rett syndrome (RTT) is a neurodevelopmental disorder caused by mutation of the X-linked MECP2 gene and characterized by developmental regression during the first few years of life. The objective of this study was to investigate if the visual evoked potential (VEP) could be used as an unbiased, quantitative biomarker to monitor brain function in RTT. METHODS: We recorded pattern-reversal VEPs in Mecp2 heterozygous female mice and 34 girls with RTT. The amplitudes and latencies of VEP waveform components were quantified, and were related to disease stage, clinical severity, and MECP2 mutation type in patients. Visual acuity was also assessed in both mice and patients by modulating the spatial frequency of the stimuli. RESULTS: Mecp2 heterozygous female mice and RTT patients exhibited a similar decrease in VEP amplitude that was most striking in the later stages of the disorder. RTT patients also displayed a slower recovery from the principal peak of the VEP response that was impacted by MECP2 mutation type. When the spatial frequency of the stimulus was increased, both patients and mice displayed a deficit in discriminating smaller patterns, indicating lower visual spatial acuity in RTT. INTERPRETATION: VEP is a method that can be used to assess brain function across species and in children with severe disabilities like RTT. Our findings support the introduction of standardized VEP analysis in clinical and research settings to probe the neurobiological mechanism underlying functional impairment and to longitudinally monitor progression of the disorder and response to treatment. This article is protected by copyright. All rights reserved.
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8. Lever AG, Geurts HM. {{Age-related differences in cognition across the adult lifespan in autism spectrum disorder}}. {Autism Res}. 2015.
It is largely unknown how age impacts cognition in autism spectrum disorder (ASD). We investigated whether age-related cognitive differences are similar, reduced or increased across the adult lifespan, examined cognitive strengths and weaknesses, and explored whether objective test performance is related to subjective cognitive challenges. Neuropsychological tests assessing visual and verbal memory, generativity, and theory of mind (ToM), and a self-report measure assessing cognitive failures were administered to 236 matched participants with and without ASD, aged 20-79 years (IQ > 80). Group comparisons revealed that individuals with ASD had higher scores on visual memory, lower scores on generativity and ToM, and similar performance on verbal memory. However, ToM impairments were no longer present in older (50+ years) adults with ASD. Across adulthood, individuals with ASD demonstrated similar age-related effects on verbal memory, generativity, and ToM, while age-related differences were reduced on visual memory. Although adults with ASD reported many cognitive failures, those were not associated with neuropsychological test performance. Hence, while some cognitive abilities (visual and verbal memory) and difficulties (generativity and semantic memory) persist across adulthood in ASD, others become less apparent in old age (ToM). Age-related differences characteristic of typical aging are reduced or parallel, but not increased in individuals with ASD, suggesting that ASD may partially protect against an age-related decrease in cognitive functioning. Despite these findings, adults with ASD experience many cognitive daily challenges, which highlights the need for adequate social support and the importance of further research into this topic, including longitudinal studies. Autism Res. 2015. (c) 2015 International Society for Autism Research, Wiley Periodicals, Inc.
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9. Miles JH. {{Complex Autism Spectrum Disorders and Cutting-Edge Molecular Diagnostic Tests}}. {JAMA}. 2015; 314(9): 879-80.
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10. Mosconi MW, Sweeney JA. {{Sensorimotor dysfunctions as primary features of autism spectrum disorders}}. {Sci China Life Sci}. 2015.
Motor impairments in autism spectrum disorders (ASD) have received far less research attention than core social-communication and cognitive features. Yet, behavioral, neurophysiological, neuroimaging and histopathological studies have documented abnormal motor system development in the majority of individuals with ASD suggesting that these deficits may be primary to the disorder. There are several unique advantages to studying motor development in ASD. First, the neurophysiological substrates of motor skills have been well-characterized via animal and human lesion studies. Second, many of the single- gene disorders associated with ASD also are characterized by motor dysfunctions. Third, recent evidence suggests that the onset of motor dysfunctions may precede the emergence of social and communication deficits during the first year of life in ASD. Motor deficits documented in ASD indicate disruptions throughout the neuroaxis affecting cortex, striatum, the cerebellum and brainstem. Questions remain regarding the timing and development of motor system alterations in ASD, their association with defining clinical features, and their potential for parsing heterogeneity in ASD. Pursuing these questions through neurobiologically informed translational research holds great promise for identifying gene-brain pathways associated with ASD.
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11. Nakai N, Otsuka S, Myung J, Takumi T. {{Autism spectrum disorder model mice: Focus on copy number variation and epigenetics}}. {Sci China Life Sci}. 2015.
Autism spectrum disorder (ASD) is gathering concerns in socially developed countries. ASD is a neuropsychiatric disorder of genetic origin with high prevalence of 1%-2%. The patients with ASD characteristically show impaired social skills. Today, many genetic studies identify numerous susceptible genes and genetic loci associated with ASD. Although some genetic factors can lead to abnormal brain function linked to ASD phenotypes, the pathogenic mechanism of ASD is still unclear. Here, we discuss a new mouse model for ASD as an advanced tool to understand the mechanism of ASD.
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12. O’Nions E, Tick B, Rijsdijk F, Happe F, Plomin R, Ronald A, Viding E. {{Examining the Genetic and Environmental Associations between Autistic Social and Communication Deficits and Psychopathic Callous-Unemotional Traits}}. {PLoS One}. 2015; 10(9): e0134331.
BACKGROUND: Difficulties in appropriate social interaction are characteristic of both children with autism spectrum disorders and children with callous-unemotional traits (who are at risk of developing psychopathy). Extant experimental studies suggest that the nature of atypical social cognition that characterises these two profiles is not identical. However, ’empathizing’ difficulties have been hypothesised for both groups, raising questions about the degree of aetiological separation between social impairments that characterize each disorder. This study explored the relative contribution of independent vs. shared aetiological influences to social and communication impairments associated with autistic traits and callous-unemotional traits, indexed by parent-report in a population-based cohort of twins. METHODS: Participants were over 5,000 twin pairs from a UK cohort (the Twins Early Development Study; TEDS), assessed for callous-unemotional traits at 7 years and autistic social and communication impairments at 8 years. Multivariate model-fitting was used to explore the relative contribution of independent vs. overlapping genetic/environmental influences on these traits. RESULTS: Both social and communication impairments and callous-unemotional traits were highly heritable, although the genetic and environmental influences accounting for individual differences on each domain were predominantly independent. CONCLUSIONS: Extant evidence from experimental and neuro-imaging studies has suggested that, despite some superficially overlapping behaviours, the social difficulties seen in children with autism spectrum disorders and callous-unemotional traits are largely distinct. The current study is the first to demonstrate considerable aetiological independence of the social interaction difficulties seen in children with autism spectrum disorders and those with callous-unemotional traits.
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13. Rahko JS, Vuontela VA, Carlson S, Nikkinen J, Hurtig TM, Kuusikko-Gauffin S, Mattila ML, Jussila KK, Remes JJ, Jansson-Verkasalo EM, Aronen ET, Pauls DL, Ebeling HE, Tervonen O, Moilanen IK, Kiviniemi VJ. {{Attention and Working Memory in Adolescents with Autism Spectrum Disorder: A Functional MRI Study}}. {Child Psychiatry Hum Dev}. 2015.
The present study examined attention and memory load-dependent differences in the brain activation and deactivation patterns between adolescents with autism spectrum disorders (ASDs) and typically developing (TD) controls using functional magnetic resonance imaging. Attentional (0-back) and working memory (WM; 2-back) processing and load differences (0 vs. 2-back) were analysed. WM-related areas activated and default mode network deactivated normally in ASDs as a function of task load. ASDs performed the attentional 0-back task similarly to TD controls but showed increased deactivation in cerebellum and right temporal cortical areas and weaker activation in other cerebellar areas. Increasing task load resulted in multiple responses in ASDs compared to TD and in inadequate modulation of brain activity in right insula, primary somatosensory, motor and auditory cortices. The changes during attentional task may reflect compensatory mechanisms enabling normal behavioral performance. The inadequate memory load-dependent modulation of activity suggests diminished compensatory potential in ASD.
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14. Rankin JA, Weber RJ, Kang E, Lerner MD. {{Parent- and Self-Reported Social Skills Importance in Autism Spectrum Disorder}}. {J Autism Dev Disord}. 2015.
While social skills are commonly assessed in autism spectrum disorder (ASD), little is known about individuals’ and families’ beliefs regarding importance of these skills. Seventy-four parents and their children with ASD rated social skills importance and severity, as well as ASD-specific deficit severity. Parents and youth rated social skills as important overall; however, parents reported assertion and self-control to be more important than their children did. Severity and importance did not correlate overall. However, parent-report of responsibility deficits and importance were positively correlated, while youth-report of assertiveness deficits and importance were negatively correlated. Finally, ASD-specific social deficits were positively correlated with parent reported importance, but negatively correlated with child reported importance. Social skills importance ratings merit consideration in ASD assessment.
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15. Ratto AB, Mesibov GB. {{Autism spectrum disorders in adolescence and adulthood: Long-term outcomes and relevant issues for treatment and research}}. {Sci China Life Sci}. 2015.
The advances in research and treatment of autism spectrum disorders (ASD) over the past three decades have focused largely on early childhood and school-age years. Although ASD is a lifelong condition, there has been relatively little attention paid to ASD during the adolescent and adulthood periods. As the population of those with ASD continues to rise and age, the need to provide research and treatment for this group has become increasingly evident. This paper reviews the current literature available on symptoms, functioning, and treatment of adolescents and adults with ASD, as well as the unique issues that arise for individuals with ASD after childhood. Adulthood outcomes for ASD are generally poor, even for those with average to above average cognitive ability. Further research and additional clinical resources are needed for this rapidly increasing group.
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16. Ruzich E, Allison C, Smith P, Watson P, Auyeung B, Ring H, Baron-Cohen S. {{Subgrouping siblings of people with autism: Identifying the broader autism phenotype}}. {Autism Res}. 2015.
We investigate the broader autism phenotype (BAP) in siblings of individuals with autism spectrum conditions (ASC). Autistic traits were measured in typical controls (n = 2,000), siblings (n = 496), and volunteers with ASC (n = 2,322) using the Autism-Spectrum Quotient (AQ), both self-report and parent-report versions. Using cluster analysis of AQ subscale scores, two sibling subgroups were identified for both males and females: a cluster of low-scorers and a cluster of high-scorers. Results show that while siblings as a group have intermediate levels of autistic traits compared to control individuals and participants with ASC, when examined on a cluster level, the low-scoring sibling group is more similar to typical controls while the high-scoring group is more similar to the ASC clinical group. Further investigation into the underlying genetic and epigenetic characteristics of these two subgroups will be informative in understanding autistic traits, both within the general population and in relation to those with a clinical diagnosis. Autism Res 2015. (c) 2015 The Authors Autism Research published by Wiley Periodicals, Inc. on behalf of International Society for Autism Research.
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17. Sacco R, Lintas C, Persico AM. {{Autism genetics: Methodological issues and experimental design}}. {Sci China Life Sci}. 2015.
Autism is a complex neuropsychiatric disorder of developmental origin, where multiple genetic and environmental factors likely interact resulting in a clinical continuum between « affected » and « unaffected » individuals in the general population. During the last two decades, relevant progress has been made in identifying chromosomal regions and genes in linkage or association with autism, but no single gene has emerged as a major cause of disease in a large number of patients. The purpose of this paper is to discuss specific methodological issues and experimental strategies in autism genetic research, based on fourteen years of experience in patient recruitment and association studies of autism spectrum disorder in Italy.
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18. Sacrey LR, Bennett JA, Zwaigenbaum L. {{Early Infant Development and Intervention for Autism Spectrum Disorder}}. {J Child Neurol}. 2015.
OBJECTIVE: The objective is to overview recent findings on early detection/diagnosis of autism spectrum disorders, as well as clinical trials of early interventions for toddlers at risk for/diagnosed with autism spectrum disorder. FINDINGS: Prospective studies of infants at high risk of autism spectrum disorder have yielded significant advances in understanding early development in autism spectrum disorder. Findings from prospective studies indicate that abnormalities in social communication and repetitive behaviors emerge during the second year, whereas additional « prodromal features » (motor and sensory abnormalities) emerge in the first year. Subsequently, exciting progress has been made in establishing the efficacy of autism spectrum disorder-specific interventions for toddlers as young as 15 months. Finally, efforts occur to characterize autism spectrum disorder-specific characteristics in genetic syndromes with concurrent autism spectrum disorder symptomatology. CONCLUSION: Substantial progress in characterizing early developmental trajectories as well as the identification of specific behavioral markers has aided early detection. Work remains to ensure that research findings are translated into clinical practice for uptake in the health care system.
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19. Saffen D. {{The genetic architecture of autism spectrum disorders (ASDs) and the potential importance of common regulatory genetic variants}}. {Sci China Life Sci}. 2015.
Currently, there is great interest in identifying genetic variants that contribute to the risk of developing autism spectrum disorders (ASDs), due in part to recent increases in the frequency of diagnosis of these disorders worldwide. While there is nearly universal agreement that ASDs are complex diseases, with multiple genetic and environmental contributing factors, there is less agreement concerning the relative importance of common vs rare genetic variants in ASD liability. Recent observations that rare mutations and copy number variants (CNVs) are frequently associated with ASDs, combined with reduced fecundity of individuals with these disorders, has led to the hypothesis that ASDs are caused primarily by de novo or rare genetic mutations. Based on this model, large-scale whole-genome DNA sequencing has been proposed as the most appropriate method for discovering ASD liability genes. While this approach will undoubtedly identify many novel candidate genes and produce important new insights concerning the genetic causes of these disorders, a full accounting of the genetics of ASDs will be incomplete absent an understanding of the contributions of common regulatory variants, which are likely to influence ASD liability by modifying the effects of rare variants or, by assuming unfavorable combinations, directly produce these disorders. Because it is not yet possible to identify regulatory genetic variants by examination of DNA sequences alone, their identification will require experimentation. In this essay, I discuss these issues and describe the advantages of measurements of allelic expression imbalance (AEI) of mRNA expression for identifying cis-acting regulatory variants that contribute to ASDs.
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20. Simmons ES, Paul R, Shic F. {{Brief Report: A Mobile Application to Treat Prosodic Deficits in Autism Spectrum Disorder and Other Communication Impairments: A Pilot Study}}. {J Autism Dev Disord}. 2015.
This study examined the acceptability of a mobile application, SpeechPrompts, designed to treat prosodic disorders in children with ASD and other communication impairments. Ten speech-language pathologists (SLPs) in public schools and 40 of their students, 5-19 years with prosody deficits participated. Students received treatment with the software over eight weeks. Pre- and post-treatment speech samples and student engagement data were collected. Feedback on the utility of the software was also obtained. SLPs implemented the software with their students in an authentic education setting. Student engagement ratings indicated students’ attention to the software was maintained during treatment. Although more testing is warranted, post-treatment prosody ratings suggest that SpeechPrompts has potential to be a useful tool in the treatment of prosodic disorders.
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21. Stark KH, Barnes JC, Young ND, Gabriels RL. {{Brief Report: Understanding Crisis Behaviors in Hospitalized Psychiatric Patients with Autism Spectrum Disorder-Iceberg Assessment Interview}}. {J Autism Dev Disord}. 2015.
Children and adolescents with autism spectrum disorder (ASD) are at risk for emotional dysregulation and behavior problems that can escalate to levels requiring psychiatric hospitalization. Evaluating the etiology of such behaviors can be challenging for health care providers, as individuals with ASD can have difficulty self-reporting concerns. This brief report introduces the Iceberg Assessment Interview (IAI), a tool to organize and elucidate the assessment of issues potentially underlying problem behaviors. A summary of IAIs from a chart review of patients ages 5-18 with ASD (n = 23) admitted to a specialized psychiatric hospital unit illustrates the clinical utility of this tool. Summarized IAI data includes presenting crisis behaviors, caregiver-perceived environmental conditions, and underlying psychosocial and medical problems.
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22. Tager-Flusberg H. {{Defining language impairments in a subgroup of children with autism spectrum disorder}}. {Sci China Life Sci}. 2015.
Autism spectrum disorder (ASD) is diagnosed on the basis of core impairments in pragmatic language skills, which are found across all ages and subtypes. In contrast, there is significant heterogeneity in language phenotypes, ranging from nonverbal to superior linguistic abilities, as defined on standardized tests of vocabulary and grammatical knowledge. The majority of children are verbal but impaired in language, relative to age-matched peers. One hypothesis is that this subgroup has ASD and co-morbid specific language impairment (SLI). An experiment was conducted comparing children with ASD to children with SLI and typically developing controls on aspects of language processing that have been shown to be impaired in children with SLI: repetition of nonsense words. Patterns of performance among the children with ASD and language impairment were similar to those with SLI, and contrasted with the children with ASD and no language impairment and typical controls, providing further evidence for the hypothesis that a subgroup of children with ASD has co-morbid SLI. The findings are discussed in the context of brain imaging studies that have explored the neural bases of language impairment in ASD and SLI, and overlap in the genes associated with elevated risk for these disorders.
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23. Tammimies K, Marshall CR, Walker S, Kaur G, Thiruvahindrapuram B, Lionel AC, Yuen RK, Uddin M, Roberts W, Weksberg R, Woodbury-Smith M, Zwaigenbaum L, Anagnostou E, Wang Z, Wei J, Howe JL, Gazzellone MJ, Lau L, Sung WW, Whitten K, Vardy C, Crosbie V, Tsang B, D’Abate L, Tong WW, Luscombe S, Doyle T, Carter MT, Szatmari P, Stuckless S, Merico D, Stavropoulos DJ, Scherer SW, Fernandez BA. {{Molecular Diagnostic Yield of Chromosomal Microarray Analysis and Whole-Exome Sequencing in Children With Autism Spectrum Disorder}}. {JAMA}. 2015; 314(9): 895-903.
IMPORTANCE: The use of genome-wide tests to provide molecular diagnosis for individuals with autism spectrum disorder (ASD) requires more study. OBJECTIVE: To perform chromosomal microarray analysis (CMA) and whole-exome sequencing (WES) in a heterogeneous group of children with ASD to determine the molecular diagnostic yield of these tests in a sample typical of a developmental pediatric clinic. DESIGN, SETTING, AND PARTICIPANTS: The sample consisted of 258 consecutively ascertained unrelated children with ASD who underwent detailed assessments to define morphology scores based on the presence of major congenital abnormalities and minor physical anomalies. The children were recruited between 2008 and 2013 in Newfoundland and Labrador, Canada. The probands were stratified into 3 groups of increasing morphological severity: essential, equivocal, and complex (scores of 0-3, 4-5, and >/=6). EXPOSURES: All probands underwent CMA, with WES performed for 95 proband-parent trios. MAIN OUTCOMES AND MEASURES: The overall molecular diagnostic yield for CMA and WES in a population-based ASD sample stratified in 3 phenotypic groups. RESULTS: Of 258 probands, 24 (9.3%, 95%CI, 6.1%-13.5%) received a molecular diagnosis from CMA and 8 of 95 (8.4%, 95%CI, 3.7%-15.9%) from WES. The yields were statistically different between the morphological groups. Among the children who underwent both CMA and WES testing, the estimated proportion with an identifiable genetic etiology was 15.8% (95%CI, 9.1%-24.7%; 15/95 children). This included 2 children who received molecular diagnoses from both tests. The combined yield was significantly higher in the complex group when compared with the essential group (pairwise comparison, P = .002). [table: see text]. CONCLUSIONS AND RELEVANCE: Among a heterogeneous sample of children with ASD, the molecular diagnostic yields of CMA and WES were comparable, and the combined molecular diagnostic yield was higher in children with more complex morphological phenotypes in comparison with the children in the essential category. If replicated in additional populations, these findings may inform appropriate selection of molecular diagnostic testing for children affected by ASD.
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24. Wang R, Liu L, Liu J. {{A new approach to the diagnosis of deficits in processing faces: Potential application in autism research}}. {Sci China Life Sci}. 2015.
Deficits in social communication are one of the behavioral signatures of autism spectrum disorder (ASD). Because faces are arguably the most important social stimuli that we encounter in everyday life, investigating the ability of individuals with ASD to process faces is thought to be important for understanding the nature of ASD. However, although a considerable body of evidence suggests that ASD individuals show specific impairments in face processing, a significant number of studies argue otherwise. Through a literature review, we found that this controversy is largely attributable to the different face tests used across different studies. Therefore, a more reliable and valid face test is needed. To this end, we performed a meta-analysis on data gleaned from a variety of face tests conducted on individuals with developmental prosopagnosia (DP) who suffer a selective deficit in face processing. Based on this meta-analysis, we selected an old/new face recognition test that relies on face memory as a standard diagnostic test for measuring specific face processing deficits. This test not only reliably reflects DP individuals’ subjective experiences with faces in their daily lives, but also effectively differentiates deficits in face processing from deficits caused by other general problems. In addition, DP individuals’ performance in this test predicts their performance in a variety of face tests that examine specific components of face processing (e.g., holistic processing of faces). Finally, this test can be easily administrated and is not overly sensitive to prior knowledge. In summary, this test can be used to evaluate face-processing ability, and it helped to resolve the controversy whether individuals with ASD exhibit face-processing deficits.
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25. Wong VC, Fung CW, Lee SL, Wong PT. {{Review of evolution of clinical, training and educational services and research program for autism spectrum disorders in Hong Kong}}. {Sci China Life Sci}. 2015.
The evolution of a local fragmented model of services for children with autism in Hong Kong emerged gradually over the past three decades with lack of government funding or support. This had been due to increasing number of children with autism being detected and referred for earlier assessment. With increasing pressure from parents due to long waiting time for assessment and training services and the increasing polarization by mass media there had been a gradual increasing public awareness over the past five years. Though still highly fragmented in the availability of services, there is a growing « business model » available in the community due to increasing need and lack of public funding for support. There is a lack of strategic planning for medical diagnostic and management issues in Hong Kong. Our University of Hong Kong based Autism Research Program was pioneered in 1985 based on the increasing load of autism cases referred for assessment for other developmental problems and diagnosed as Autism in the Duchess of Kent Children’s Hospital. As the first author has been the staff of the University of Hong Kong, this program flourished as a research based program. The benefits of early identification and intervention of autism spectrum disorder (ASD) had been increasingly recognized, and with the increased public awareness and increasing trend of earlier diagnosis, there has been a continuously high demand from parents for earlier assessment and training for children suspected to have ASD. This model had not received extra funding for this integrated program for research, teaching and training in autism. We had to apply for various donations and grants to support the development of this pioneer program. The research output and organization of forums for public education and awareness are reviewed. The latter part of the paper reports the summary of clinical profile of autism cases (N=1441) assessed from 1985 to 2010 June under the University of Hong Kong. As the waiting time for initial developmental assessment for any children in Hong Kong is 12?24 months, we also report our preliminary experience with a newly launched triaging service provision for children suspected to be ASD since 2009, including multi-disciplinary assessment and parallel interim training in our university affiliated child assessment centre in Hong (N=89).
