Autism Spectrum Disorder Sample Research Articles

A microcosting and cost-consequence analysis of clinical genomic testing strategies in autism spectrum disorder.

PurposeWhole-exome (WES) and whole-genome sequencing (WGS) increase the diagnostic yield in autism spectrum disorder (ASD) compared to chromosomal microarray (CMA), but there have been no comprehensive cost analyses. The objective was to perform such an assessment of CMA, WES, and WGS and compare the incremental cost per additional positive finding in hypothetical testing scenarios.MethodsFive-year patient and program costs were estimated from an institutional perspective. WES and WGS estimates were based on HiSeq 2500 with an additional WGS estimate for HiSeq X platforms. Parameter uncertainty was assessed with probabilistic and deterministic sensitivity analysis.ResultsThe cost per ASD sample was CAD$1,655 (95% CI: 1,611; 1,699) for WES, CAD$2,851 (95% CI: 2,750; 2,956) for WGS on HiSeq X, and CAD$5,519 (95% CI: 5,244; 5,785) on HiSeq 2500, compared to CAD$744 (95% CI 714, 773) for CMA. The incremental cost was over CAD$25,000 per additional positive finding if CMA was replaced by newer technology.ConclusionWhile costs for WES and WGS remain high, future reductions in material and equipment costs, and increased understanding of newly discovered variants and variants of unknown significance will lead to improved value.

Face perception and learning in autism spectrum disorders.

Autism Spectrum Disorder (ASD) is characterized by impairment in social communication and restricted and repetitive interests. 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 vary 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 three 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 information and understanding.

Gene-set analysis shows association between FMRP targets and autism spectrum disorder.

Autism spectrum disorder (ASD) is a heterogeneous group of disorders characterized by problems with social interaction, communication, and repetitive and restricted behavior. Despite its high heritability and the substantial progress made in elucidating genetic associations, the corresponding biological mechanisms are largely unknown. Our objective is to investigate the contribution of common genetic variation to biological pathways functionally involved in ASD. We conducted gene-set analyses to identify ASD-associated functional biological pathways using the statistical tools MAGMA and INRICH. Gene-set selection was based on previously reported associations with psychiatric disorders and resulted in testing of specific synaptic and glial sets, a glutamate pathway gene-set, mitochondrial gene-sets and gene-sets consisting of fragile X mental retardation protein (FMRP) targets. In total 32 gene-sets were tested. We used Psychiatric Genomics Consortium genome-wide association studies summary statistics of ASD. The study is based on the largest ASD sample to date (N=5305). We found one significantly associated gene-set consisting of FMRP-targeting transcripts (MAGMA: p corr.=0.014, INRICH: p corr.=0.031; all competitive P-values). The results indicate the involvement of FMRP-targeted transcripts in ASD in common genetic variation. This novel finding is in line with the literature as FMRP has been linked to fragile X syndrome, ASD and cognitive development in whole-exome sequencing and copy number variant studies. This gene-set has also been linked to Schizophrenia suggesting that FMRP-targeted transcripts might be involved in a general mechanism with shared genetic etiology between psychiatric disorders.

Comparisons of the Factor Structure and Measurement Invariance of the Spence Children\u2019s Anxiety Scale\u2014Parent Version in Children with Autism Spectrum Disorder and Typically Developing Anxious Children

The Spence Children’s Anxiety Scale—Parent version (SCAS-P) is often used to assess anxiety in children with autism spectrum disorder (ASD), however, little is known about the validity of the tool in this population. The aim of this study was to determine whether the SCAS-P has the same factorial validity in a sample of young people with ASD (n = 285), compared to a sample of typically developing young people with anxiety disorders (n = 224). Poor model fit with all of the six hypothesised models precluded invariance testing. Exploratory factor analysis indicated that different anxiety phenomenology characterises the two samples. The findings suggest that cross-group comparisons between ASD and anxious samples based on the SCAS-P scores may not always be appropriate.

Social attention and autism symptoms in high functioning women with autism spectrum disorders

BackgroundResearch has suggested a different, less visible, clinical manifestation of Autism Spectrum Disorders (ASD) in females. There is, however, limited research into possible underlying mechanisms explaining the female phenotype. AimsThis study investigates social attention in females with ASD. Methods and procedures26 women diagnosed with ASD and 26 typical female controls were shown three video clips containing intense emotions. Social attention was assessed by measuring eye fixation patterns during the video clips. Autism symptoms were assessed using the informant reported Social Responsiveness Scale (SRS). Outcome and resultsResults show normal time to first fixation to the face, but lower fixation duration to the face in women with ASD. Analyzing the visual patterns further, there were similar impairments in fixation to mouth, eyes and other facial areas. Relating social attention to autism symptoms revealed several significant correlations within the ASD group. Conclusions and implicationsWomen with ASD show abnormalities in social attention and these abnormalities are related to level of autism symptoms. In contrast to other studies which investigate male dominated ASD samples, a hyperfocus to the mouth area could not be found.

IQ profiles and clinical symptoms of Chinese school-aged boys with autism spectrum disorder

Background and objectiveThe cognitive abilities of individuals with autism spectrum disorder (ASD) vary widely, but studies have not yet examined Chinese school-aged boys with ASD in a systematic way.This study aims to explore the IQ profile of Chinese school-aged boys with ASD; and the correlation of IQ and related symptoms. MethodsThirty-one boys with ASD and forty-eight typically developing (TD) boys were examined using the WISC-IV Chinese version. The relationship between IQ index scores and ASD symptoms was explored. ResultsFor boys with ASD, in comparison to the TD Group, significantly lower scores were found for the Verbal Comprehension Index (VCI), Processing Speed Index (PSI) and Full Scale IQ (FSIQ). Examination of the Verbal IQ-Nonverbal IQ pattern across groups revealed differences between the ASD and the TD groups (x2=13.282, p=.001). For the ASD sample, a negative correlation was observed between all the Index scores and the Level & Consistency of Intellectual Response score. ConclusionsOur results indicated that Chinese school-aged boys with ASD show a different pattern of intellectual ability from their TD peers, with equivalent abilities in the PRI and WMI.

Abnormal Size-Dependent Modulation of Motion Perception in Children with Autism Spectrum Disorder (ASD)

Excitation/Inhibition (E/I) imbalance in neural networks is now considered among the core neural underpinnings of autism psychopathology. In motion perception at least two phenomena critically depend on E/I balance in visual cortex: spatial suppression (SS), and spatial facilitation (SF) corresponding to impoverished or improved motion perception with increasing stimuli size, respectively. While SS is dominant at high contrast, SF is evident for low contrast stimuli, due to the prevalence of inhibitory contextual modulations in the former, and excitatory ones in the latter case. Only one previous study (Foss-Feig et al., 2013) investigated SS and SF in Autism Spectrum Disorder (ASD). Our study aimed to replicate previous findings, and to explore the putative contribution of deficient inhibitory influences into an enhanced SF index in ASD—a cornerstone for interpretation proposed by Foss-Feig et al. (2013). The SS and SF were examined in 40 boys with ASD, broad spectrum of intellectual abilities (63 < IQ < 127) and 44 typically developing (TD) boys, aged 6–15 years. The stimuli of small (1°) and large (12°) radius were presented under high (100%) and low (1%) contrast conditions. Social Responsiveness Scale and Sensory Profile Questionnaire were used to assess the autism severity and sensory processing abnormalities. We found that the SS index was atypically reduced, while SF index abnormally enhanced in children with ASD. The presence of abnormally enhanced SF in children with ASD was the only consistent finding between our study and that of Foss-Feig et al. While the SS and SF indexes were strongly interrelated in TD participants, this correlation was absent in their peers with ASD. In addition, the SF index but not the SS index correlated with the severity of autism and the poor registration abilities. The pattern of results is partially consistent with the idea of hypofunctional inhibitory transmission in visual areas in ASD. Nonetheless, the absence of correlation between SF and SS indexes paired with a strong direct link between abnormally enhanced SF and autism symptoms in our ASD sample emphasizes the role of the enhanced excitatory influences by themselves in the observed abnormalities in low-level visual phenomena found in ASD.

Gaze-Contingent Display Changes as New Window on Analytical and Holistic Face Perception in Children With Autism Spectrum Disorder.

The strength of holistic face perception in children with autism spectrum disorder (ASD) was evaluated by applying the gaze-contingent mask and window technique to a face matching and discrimination task in 6- to 14-year-old children with (n=36) and without ASD (n=47), and by examining fixation patterns. Behavioral results suggested a slower and less efficient face processing in the ASD sample compared with the matched control group. Comparing the moving mask and window conditions revealed a reduced holistic face processing bias in the younger age group but not in the older sample. Preferential viewing patterns revealed both similarities and differences between both participant groups.

Measuring Theory of Mind in Adults with Autism Spectrum Disorder

Deficits in Theory of Mind (ToM)—the ability to interpret others’ beliefs, intentions and emotions—undermine the ability of individuals with Autism Spectrum Disorder (ASD) to interact in socially normative ways. This study provides psychometric data for the Adult-Theory of Mind (A-ToM) measure using video-scenarios based in part on Happé’s (Instructions for theory of mind story task, 1999) Strange Stories test. The final items discriminated IQ-matched adults with ASD from controls on the social but not the physical items. Additional validity data included a two-component principal components solution, correlations with existing ToM scales, and the absence of correlations with self-report measures of empathy and social anxiety (not requiring inferences about the intent of others). The expected group differences in ToM were accompanied by marked variability in the ASD sample.

Sensory, Emotional and Cognitive Contributions to Anxiety in Autism Spectrum Disorders.

Severe symptoms of anxiety add substantial additional burden to many individuals diagnosed with Autism Spectrum Disorder (ASD). Improved understanding of specific factors that contribute to anxiety in ASD can aid research regarding the causes of autism and also provide targets for more effective intervention. This mini-review article focuses on emerging evidence for three concepts that appear to be related to each other and which also strongly predict anxiety in ASD samples. Atypical sensory function is included in the diagnostic criteria for ASD and is likely an important contributor to anxiety. Difficulties in understanding and labeling emotions (alexithymia), although a co-morbidity, may arise in part from atypical sensory function and can lead to confusion and uncertainty about how to respond to social and emotional situations. Intolerance of uncertainty (IU) describes people who have a particularly hard time with ambiguity and is known to be a key mechanism underlying some anxiety disorders. While evidence for linking these ideas is to date incomplete, we put forward a model including each concept as a framework for future studies. Specifically, we propose that IU is a critical mediator for anxiety in ASD, and explore the relationships between sensory function, alexithymia and IU. We further explore the role of the medial prefrontal cortex (mPFC) in regulating emotional response, in connection with limbic and insula-based networks, and suggest that disrupted integration in these networks underlies difficulties with habituation to strong emotional stimuli, which results in an enhanced perception of threat in many people with ASD. Behavioral and biologically-based treatments for anxiety in ASD will benefit from attending to these specific mechanisms as adjunct to traditional interventions.

Variation in Gene Expression in Autism Spectrum Disorders: An Extensive Review of Transcriptomic Studies.

Autism spectrum disorders (ASDs) are a group of complex neurodevelopmental conditions that present in early childhood and have a current estimated prevalence of about 1 in 68 US children, 1 in 42 boys. ASDs are heterogeneous, and arise from epigenetic, genetic and environmental origins, yet, the exact etiology of ASDs still remains unknown. Individuals with ASDs are characterized by having deficits in social interaction, impaired communication and a range of stereotyped and repetitive behaviors. Currently, a diagnosis of ASD is based solely on behavioral assessments and phenotype. Hundreds of diverse ASD susceptibility genes have been identified, yet none of the mutations found account for more than a small subset of autism cases. Therefore, a genetic diagnosis is not yet possible for the majority of the ASD population. The susceptibility genes that have been identified are involved in a wide and varied range of biological functions. Since the genetics of ASDs is so diverse, information on genome function as provided by transcriptomic data is essential to further our understanding. Gene expression studies have been extremely useful in comparing groups of individuals with ASD and control samples in order to measure which genes (or group of genes) are dysregulated in the ASD group. Transcriptomic studies are essential as a key link between measuring protein levels and analyzing genetic information. This review of recent autism gene expression studies highlights genes that are expressed in the brain, immune system, and processes such as cell metabolism and embryology. Various biological processes have been shown to be implicated with ASD individuals as well as differences in gene expression levels between different types of biological tissues. Some studies use gene expression to attempt to separate autism into different subtypes. An updated list of genes shown to be significantly dysregulated in individuals with autism from all recent ASD expression studies will help further research isolate any patterns useful for diagnosis or understanding the mechanisms involved. The functional relevance of transcriptomic studies as a method of classifying and diagnosing ASD cannot be underestimated despite the possible limitations of transcriptomic studies.

Parental Age And Differential Risk For Asd, Adhd, Ocd And Tic Disorders: Data From A Large National Cohort

Background Parental age is known to contribute to risk for various neurodevelopmental disorders, including autism spectrum disorder (ASD), schizophrenia, and intellectual disability. In this study we used a population-based cohort to assess the role of parental age in risk across childhood- and adolescent- onset neuropsychiatric disorders including ASD, attention-deficit hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD) and Tourette syndrome/chronic tic disorder (TS/CT). Methods Our study cohort included all singleton births, with age data on both parents (n=1,490,745), in Denmark between 1980 and 2007, followed through December 31, 2013. Cases of ASD, ADHD, OCD and TS/CT were identified in the Danish Psychiatric Central Register and the National Patient Register. Both the ADHD and ASD samples overlapped with those in recent reports, while the OCD and TS/CT samples had not been analyzed previously. Associations with parental age were modeled by a cubic spline with 4 knots in stratified Cox regression in which each birth year has its own baseline diagnostic rate while adjusting for the age of the opposite parent. Results Cases identified included 16,083 individuals diagnosed with ASD, 25,307 diagnosed with ADHD, 5,324 diagnosed with OCD and 4,666 individuals diagnosed with TS/CT. Younger maternal age was significantly associated with increased risk for ADHD (>1.4-fold increased risk, comparing point estimates of 25 yo mothers to the reference of 30 yo mothers), as well as with increased risk for ASD and for TS/CT. Moreover, association between maternal age and ASD risk followed a U-shaped curve, with increased risk associated with both younger and older mothers. Younger paternal age was also associated with significantly increased risk for ADHD. Advanced paternal age was associated with significantly increased risk for ASD (>1.2 fold at 40 yo), as well as ADHD. Discussion Parental age confers differential risk for different child- and adolescent- onset psychiatric disorders and the findings suggest a role for specific, known mechanisms in some of the disorders. Findings of advanced paternal age and risk for ASD and ADHD suggest a role for (1) de novo mutations and/or (2) epigenetic changes in both disorders. The association of younger maternal age with ASD, ADHD and TS/CT suggest that (3) maternal behaviors association with earlier parenting and/or (4) genetic factors that lead to both increased risk for these disorders and younger ages for child bearing are a part of the risk architecture for these disorders. Our results are consistent with a model of distinct and overlapping risk architecture for child- and adolescent- onset neuropsychiatric disease.

Genome-wide changes in lncRNA, splicing, and regional gene expression patterns in autism.

Autism spectrum disorder (ASD) involves substantial genetic contributions. These contributions are profoundly heterogeneous but may converge on common pathways that are not yet well understood. Here, through post-mortem genome-wide transcriptome analysis of the largest cohort of samples analysed so far, to our knowledge, we interrogate the noncoding transcriptome, alternative splicing, and upstream molecular regulators to broaden our understanding of molecular convergence in ASD. Our analysis reveals ASD-associated dysregulation of primate-specific long noncoding RNAs (lncRNAs), downregulation of the alternative splicing of activity-dependent neuron-specific exons, and attenuation of normal differences in gene expression between the frontal and temporal lobes. Our data suggest that SOX5, a transcription factor involved in neuron fate specification, contributes to this reduction in regional differences. We further demonstrate that a genetically defined subtype of ASD, chromosome 15q11.2-13.1 duplication syndrome (dup15q), shares the core transcriptomic signature observed in idiopathic ASD. Co-expression network analysis reveals that individuals with ASD show age-related changes in the trajectory of microglial and synaptic function over the first two decades, and suggests that genetic risk for ASD may influence changes in regional cortical gene expression. Our findings illustrate how diverse genetic perturbations can lead to phenotypic convergence at multiple biological levels in a complex neuropsychiatric disorder.

ADHD severity as it relates to comorbid psychiatric symptomatology in children with Autism Spectrum Disorders (ASD)

Comorbid diagnoses identified in pediatric samples have been correlated with a range of outcomes, including greater levels of emotional, behavioral, and educational impairment and the need for more intensive treatment. Given that previous research has documented high levels of comorbid Attention-Deficit/Hyperactivity Disorder (ADHD) in children with Autism Spectrum Disorders (ASD), this study closely examines the relationship between parent-reported ADHD symptoms (i.e., Conners' Parent Rating Scale, Revised [CPRS-R]) and the prevalence of additional comorbid psychiatric diagnoses in a pediatric ASD sample (n=99). Regression analyses revealed that greater severity of ADHD symptomatology was significantly related to a greater number of comorbid psychiatric diagnoses, as identified using the Diagnostic Interview for Children and adolescents, 4th Edition (DICA-IV). Additionally, more severe ADHD symptoms were also associated with higher levels of symptom severity on Child Behavior Checklist (CBCL) syndrome subscales. Interestingly, increasing severity of ASD symptomatology, as measured by the Autism Diagnostic Interview, Revised (ADI-R), was not associated with a higher prevalence of comorbid psychiatric diagnoses or CBCL syndrome severity. Our study concluded that higher levels of ADHD severity—not ASD severity—were associated with a higher prevalence of comorbid psychiatric symptomatology in school-age children with ASD. These findings may encourage clinicians to thoroughly assess ADHD symptomatology in ASD children to better inform treatment planning.

Blood transcriptomic comparison of individuals with and without autism spectrum disorder: A combined-samples mega-analysis.

Blood-based microarray studies comparing individuals affected with autism spectrum disorder (ASD) and typically developing individuals help characterize differences in circulating immune cell functions and offer potential biomarker signal. We sought to combine the subject-level data from previously published studies by mega-analysis to increase the statistical power. We identified studies that compared ex vivo blood or lymphocytes from ASD-affected individuals and unrelated comparison subjects using Affymetrix or Illumina array platforms. Raw microarray data and clinical meta-data were obtained from seven studies, totaling 626 affected and 447 comparison subjects. Microarray data were processed using uniform methods. Covariate-controlled mixed-effect linear models were used to identify gene transcripts and co-expression network modules that were significantly associated with diagnostic status. Permutation-based gene-set analysis was used to identify functionally related sets of genes that were over- and under-expressed among ASD samples. Our results were consistent with diminished interferon-, EGF-, PDGF-, PI3K-AKT-mTOR-, and RAS-MAPK-signaling cascades, and increased ribosomal translation and NK-cell related activity in ASD. We explored evidence for sex-differences in the ASD-related transcriptomic signature. We also demonstrated that machine-learning classifiers using blood transcriptome data perform with moderate accuracy when data are combined across studies. Comparing our results with those from blood-based studies of protein biomarkers (e.g., cytokines and trophic factors), we propose that ASD may feature decoupling between certain circulating signaling proteins (higher in ASD samples) and the transcriptional cascades which they typically elicit within circulating immune cells (lower in ASD samples). These findings provide insight into ASD-related transcriptional differences in circulating immune cells. © 2016 Wiley Periodicals, Inc.

Fitness to Plead: The Impact of Autism Spectrum Disorder

ABSTRACTPurpose: This study aims to investigate the cognitive deficits associated with a diagnosis of autism spectrum disorder (ASD) and their impact upon the skills necessary for fitness to plead (FTP) to a criminal charge at trial.Methodology: A between-groups study compared the performance of a group of adult participants with a diagnosis of ASD (N = 15) with a matched control group of adults with no diagnosis of ASD (N = 15) on an ecologically valid 15-min filmed vignette of typical Crown Court proceedings, during which they answered questions based upon cognitive skills required for FTP. The cognitive abilities of the participants were also assessed.Findings: Participants in the ASD group scored significantly lower than the control group on the measure of FTP. Specifically, the ASD group scored lower on questions relating to the procedures and processes of the courtroom.Research Implications: Future research using a larger ASD sample and comparisons to a nonforensic ASD sample is recommended to confirm and extend these findings, and further the development of appropriate supporting measures.Practical Implications: The current finding that individuals with ASD have a poorer understanding of the courtroom process than individuals without ASD suggests the need to support and implement special measures with this client group.Originality: This article introduces a standardized measure of FTP for use with individuals with ASD, which has not previously been available.

Investigating the Microstructural Correlation of White Matter in Autism Spectrum Disorder.

White matter microstructure forms a complex and dynamical system that is critical for efficient and synchronized brain function. Neuroimaging findings in children with autism spectrum disorder (ASD) suggest this condition is associated with altered white matter microstructure, which may lead to atypical macroscale brain connectivity. In this study, we used diffusion tensor imaging measures to examine the extent that white matter tracts are interrelated within ASD and typical development. We assessed the strength of inter-regional white matter correlations between typically developing and ASD diagnosed individuals. Using hierarchical clustering analysis, clustering patterns of the pairwise white matter correlations were constructed and revealed to be different between the two groups. Additionally, we explored the use of graph theory analysis to examine the characteristics of the patterns formed by inter-regional white matter correlations and compared these properties between ASD and typical development. We demonstrate that the ASD sample has significantly less coherence in white matter microstructure across the brain compared to that in the typical development sample. The ASD group also presented altered topological characteristics, which may implicate less efficient brain networking in ASD. These findings highlight the potential of graph theory based network characteristics to describe the underlying networks as measured by diffusion magnetic resonance imaging and furthermore indicates that ASD may be associated with altered brain network characteristics. Our findings are consistent with those of a growing number of studies and hypotheses that have suggested disrupted brain connectivity in ASD.

Exploiting aberrant mRNA expression in autism for gene discovery and diagnosis.

Autism spectrum disorder (ASD) is characterized by substantial phenotypic and genetic heterogeneity, which greatly complicates the identification of genetic factors that contribute to the disease. Study designs have mainly focused on group differences between cases and controls. The problem is that, by their nature, group difference-based methods (e.g., differential expression analysis) blur or collapse the heterogeneity within groups. By ignoring genes with variable within-group expression, an important axis of genetic heterogeneity contributing to expression variability among affected individuals has been overlooked. To this end, we develop a new gene expression analysis method-aberrant gene expression analysis, based on the multivariate distance commonly used for outlier detection. Our method detects the discrepancies in gene expression dispersion between groups and identifies genes with significantly different expression variability. Using this new method, we re-visited RNA sequencing data generated from post-mortem brain tissues of 47 ASD and 57 control samples. We identified 54 functional gene sets whose expression dispersion in ASD samples is more pronounced than that in controls, as well as 76 co-expression modules present in controls but absent in ASD samples due to ASD-specific aberrant gene expression. We also exploited aberrantly expressed genes as biomarkers for ASD diagnosis. With a whole blood expression data set, we identified three aberrantly expressed gene sets whose expression levels serve as discriminating variables achieving >70% classification accuracy. In summary, our method represents a novel discovery and diagnostic strategy for ASD. Our findings may help open an expression variability-centered research avenue for other genetically heterogeneous disorders.

Language Ability Predicts Cortical Structure and Covariance in Boys with Autism Spectrum Disorder.

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.

Atypical Amygdala Response to Fear Conditioning in Autism Spectrum Disorder

BackgroundAnxiety is the most common comorbid psychiatric concern in individuals diagnosed with autism spectrum disorder (ASD) and can cause significant functional impairment. Fear conditioning tasks offer a useful neurodevelopmental model for anxiety, yet there are no published neuroimaging studies of fear conditioning using ASD samples. MethodsTwenty adults diagnosed with ASD and 19 healthy adult control subjects completed a standard fear conditioning and extinction paradigm while undergoing functional magnetic resonance imaging scanning. A burst of air on the base of the neck was the unconditioned stimulus. Participants returned 1 day later for scanning during an extinction recall phase. A priori regions of interest were analyzed with a familywise error correction rate < 0.05. ResultsAll regions of interest demonstrated significantly greater response to threat than safe conditions during initial fear acquisition. Compared with age-matched control subjects, the ASD group showed a significantly decreased differential response to threat versus safe cues in right amygdala during the initial fear acquisition phase and decreased response in left amygdala during the first run of extinction recall on the second day of scanning. ConclusionsSymptoms of severe anxiety in ASD may arise from atypical neural mechanisms especially related to the differentiation of threat versus safe cues. An inability to effectively identify safety contexts may underlie chronically increased levels of anxiety in many individuals diagnosed with ASD.