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Clinicians form initial impressions about a child's diagnosis based on behavioral features, but research has not yet identified specific behaviors to guide initial diagnostic impressions. Participants were toddlers (N = 55, mean age 22.9 months) from a multi-site early detection study, referred for concern for ASD due to screening or parent/provider concern. Within 5 min of meeting a child, clinicians noted ASD or non-ASD impression, confidence in impression, and behaviors that informed their impression. These clinicians also determined final diagnoses for each child. When a child's final diagnosis was ASD (n = 35), senior clinicians formed an initial impression of ASD in 22 cases (63%) but missed 13 cases (37%). When final diagnosis was non-ASD (n = 20), senior clinicians made an initial impression of non-ASD in all cases (100%). Results were similar among junior clinicians. Senior and junior clinicians used the same behaviors to form accurate impressions of ASD and non-ASD: social reciprocity, nonverbal communication, and eye contact. Senior clinicians additionally used focus of attention when forming accurate impressions of ASD and non-ASD; junior clinicians used this behavior only when forming accurate non-ASD impressions. Clinicians' initial impressions of ASD are very likely to be consistent with final diagnoses, but initial impressions of non-ASD need follow-up. Toddlers who show all four atypical behaviors (social reciprocity, nonverbal communication, eye contact, and focus of attention) might receive expedited ASD diagnoses. However, presence of apparently typical behaviors should not rule out ASD; for some children a longer evaluation is necessary to allow for more opportunities to observe subtle social behavior., (© 2024 International Society for Autism Research and Wiley Periodicals LLC.)

Patients with autism spectrum disorder (ASD) often show pervasive and complex language impairments that are closely associated with aberrant structural connectivity of language networks. However, the characteristics of white matter connectivity in ASD have remained inconclusive in previous diffusion tensor imaging (DTI) studies. The current meta-analysis aimed to comprehensively elucidate the abnormality in language-related white matter connectivity in individuals with ASD. We searched PubMed, Web of Science, Scopus, and Medline databases to identify relevant studies. The standardized mean difference was calculated to measure the pooled difference in DTI metrics in each tract between the ASD and typically developing (TD) groups. The moderating effects of age, sex, language ability, and symptom severity were investigated using subgroup and meta-regression analysis. Thirty-three DTI studies involving 831 individuals with ASD and 836 TD controls were included in the meta-analysis. ASD subjects showed significantly lower fractional anisotropy or higher mean diffusivity across language-associated tracts than TD controls. These abnormalities tended to be more prominent in the left language networks than in the right. In addition, children with ASD exhibit more pronounced and pervasive disturbances in white matter connectivity than adults. These results support the under-connectivity hypothesis and demonstrate the widespread abnormal microstructure of language-related tracts in patients with ASD. Otherwise, white matter abnormalities in the autistic brain could vary depending on the developmental stage and hemisphere. LAY SUMMARY: This meta-analysis explored abnormalities in white matter connectivity in language networks of individuals with ASD. Significantly reduced white matter integrity was found in all language-associated tracts in subjects with ASD compared with TD controls. In addition, structural disturbances of language networks in the autistic brain exhibit a leftward tendency, and more prominent abnormalities are observed in younger people with ASD than in adults., (© 2022 The Authors. Autism Research published by International Society for Autism Research and Wiley Periodicals LLC.)

Social information processing (SIP) skills are critical for developing and maintaining peer relationships. Building on existing assessment techniques, Virtual Environment for SIP (VESIP TM ), a simulation-based assessment that immerses children in social decision-making scenarios, was developed. This study presents preliminary evidence of VESIP's usefulness for measuring SIP skills in children with and without autism spectrum disorders (ASD). Twenty-one children with ASD and 29 control children participated. It was hypothesized that (a) children (8-12 years old), with and without ASD, would understand and interact effectively with VESIP; (b) VESIP scores would be reliable in both populations; and (c) children with ASD would score lower on SIP domains than typically developing peers. Results supported these hypotheses. Finally, response bias was also evaluated, showing that children with ASD have different problem-solving strategies than their peers. VESIP has great potential as a scalable assessment of SIP strengths and challenges in children with and without ASD. Autism Res 2018, 11: 305-317. © 2017 International Society for Autism Research, Wiley Periodicals, Inc., Lay Summary: Children with autism spectrum disorders (ASDs) often struggle interpreting and responding to social situations. The present study suggests that an animated, simulation-based assessment approach is an effective way to measure how children with or without ASDs problem-solve challenging social situations. VESIP is an easy-to-use assessment tool that can help practitioners understand a child's particular strengths and weaknesses., (© 2017 International Society for Autism Research, Wiley Periodicals, Inc.)

In a longitudinal population-based study of 2,905 children, we investigated if infants' neuromotor development was associated with autistic traits in childhood. Overall motor development and muscle tone were examined by trained research assistants with an adapted version of Touwen's Neurodevelopmental Examination between ages 2 and 5 months. Tone was assessed in several positions and items were scored as normal, low, or high tone. Parents rated their children's autistic traits with the Social Responsiveness Scale (SRS) and the Pervasive Developmental Problems (PDP) subscale of the Child Behavior Checklist at 6 years. We defined clinical PDP if scores were >98th percentile of the norm population. Diagnosis of autism spectrum disorder (ASD) was clinically confirmed in 30 children. We observed a modest association between overall neuromotor development in infants and autistic traits. Low muscle tone in infancy predicted autistic traits measured by SRS (adjusted beta = 0.05, 95% CI for B: 0.00-0.02, P = 0.01), and PDP (adjusted beta = 0.08, 95% CI for B: 0.04-0.10, P < 0.001). Similar results emerged for the association of low muscle tone and clinical PDP (adjusted OR = 1.36, 95% CI: 1.08-1.72, P = 0.01) at age 6 years. Results remained unchanged if adjusted for child intelligence. There was no association between high muscle tone and SRS or PDP. Exclusion of children with ASD diagnosis did not change the association. This large study showed a prospective association of infant muscle tone with autistic traits in childhood. Our findings suggest that early detection of low muscle tone might be a gateway to improve early diagnosis of ASD. Autism Res 2017, 10: 757-768. © 2017 International Society for Autism Research, Wiley Periodicals, Inc., (© 2017 International Society for Autism Research, Wiley Periodicals, Inc.)

This study reports on the initial validation of the Autism Symptom Interview (ASI), School-Age, a brief (15-20 min) phone interview derived from questions from the Autism Diagnostic Interview-Revised (ADI-R). The ASI, School-Age was administered by interviewers with minimal training to parents of children ages 5 to 12 who had all been previously identified with (or referred for assessment of) ASD or another neurodevelopmental disorder. Children then underwent a comprehensive assessment to determine a best-estimate clinical diagnosis of ASD (n = 159) or non-ASD (e.g. language disorder, intellectual disability, ADHD; n = 130). Clinicians who conducted the assessments were blind to ASI results. ROC analyses compared ASI scores to clinical diagnosis. Due to the small number of participants with non-ASD diagnoses who were classified as nonverbal (i.e. not yet using phrases on a daily basis), it was not possible to assess sensitivity and specificity of the nonverbal algorithm in this sample. The verbal algorithm yielded a sensitivity of 0.87 (95% CI = 0.81-0.92) and a specificity of 0.62 (95% CI = 0.53-0.70). When used in conjunction with the Autism Diagnostic Observation Schedule (ADOS), sensitivity and specificity were 0.82 (95% CI = 0.74-0.88) and 0.92 (95% CI = 0.86-0.96), respectively. Internal consistency and test-retest reliability were both excellent. Particularly for verbal school age children, the ASI may serve as a useful tool to more quickly ascertain or classify children with ASD for research or clinical triaging purposes. Additional data collection is underway to determine the utility of the ASI in children who are younger and/or nonverbal. Autism Res 2017, 10: 78-88. © 2016 International Society for Autism Research, Wiley Periodicals, Inc., Competing Interests: Disclosure Drs. Lord, Gotham, and Bishop receive royalties for the sale of diagnostic instruments they have co-authored (ADOS, ADOS-2, and/or ADI-R). Royalties generated from any of their own research or clinical activities are donated to charity., (© 2016 International Society for Autism Research, Wiley Periodicals, Inc.)

The Social Responsiveness Scale (SRS) is an autism rating scales in widespread use, with over 20 official foreign language translations. It has proven highly feasible for quantitative ascertainment of autistic social impairment in public health settings, however, little is known about the validity of the reinforcement in Asia populations or in references to DSM5. The current study aims to evaluate psychometric properties and cross-cultural aspects of the SRS-Korean version (K-SRS).The study subjects were ascertained from three samples: a general sample from 3 regular education elementary schools (n=790), a clinical sample (n=154) of 6-12-year-olds from four psychiatric clinics, and an epidemiological sample of children with ASD, diagnosed using both DSM IV PDD, DSM5 ASD and SCD criteria (n=151). Their parents completed the K-SRS and the Autism Spectrum Screening Questionnaire(ASSQ). Descriptive statistics, correlation analyses and principal components analysis (PCA) were performed on the total population. Mean total scores on the K-SRS differed significantly between the three samples. ASSQ scores were significantly correlated with the K-SRS T-scores. PCA suggested a one-factor solution for the total population.Our results indicate that the K-SRS exhibits adequate reliability and validity for measuring ASD symptoms in Korean children with DSM IV PDD and DSM5 ASD. Our findings further suggest that it is difficult to distinguish SCD from other child psychiatric conditions using the K-SRS.This is the first study to examine the relationship between the SRS subscales and DSM5-based clinical diagnoses. This study provides cross-cultural confirmation of the factor structure for ASD symptoms and traits measured by the SRS. Autism Res 2016, 9: 970-980. © 2016 International Society for Autism Research, Wiley Periodicals, Inc., (© 2016 International Society for Autism Research, Wiley Periodicals, Inc.)

A fundamental challenge to the timely diagnosis of Autism Spectrum Disorder (ASD) is the reliance on the observation of a set of aberrant behavior. Consequently, the diagnostic process requires that the child reach an age where the behaviors would typically be exhibited. The identification of a reliable biological marker (biomarker) could be of considerable benefit to the diagnostic process. As a diagnostic biomarker, porphyrins present an attractive prospect as previous studies have reported consistent findings of children with ASD showing significant elevations in porphyrin levels in contrast to controls. Furthermore, there is some evidence that ASD severity may be associated with porphyrins, which would be a valuable characteristic of any ASD biomarker. Importantly, for practical use, porphyrins can be tested non-invasively via a sample of urine. The present study sought to investigate whether porphyrin profiles can reliably be used to (a) differentiate ASD cases from healthy controls; and (b) predict ASD severity. The study compared the porphyrin levels of three groups of children aged 2-6 years: Group 1-children diagnosed with ASD (n = 70); Group 2-healthy, normally developing siblings of children diagnosed with ASD (n = 36); and Group 3-healthy, normally developing children with no known blood relative diagnosed with ASD (n = 54). The results of logistic regression analyses failed to find support for the hypotheses that porphyrin levels could be used as a valid tool to detect ASD cases or predict severity., (© 2014 International Society for Autism Research, Wiley Periodicals, Inc.)

Investigating the underlying neural mechanisms of autism spectrum disorder (ASD) has recently been influenced by the discovery of mirror neurons. These neurons, active during both observation and execution of actions, are thought to play a crucial role in imitation and other social-communicative skills that are often impaired in ASD. In the current electroencephalographic study, we investigated mu suppression, indicating neural mirroring in children with ASD between the ages of 24 and 48 months and age-matched typically developing children, during observation of goal-directed actions and non-goal-directed mimicked hand movements, as well as during action execution. Results revealed no significant group differences with significant central mu suppression in the ASD children and control children during both execution and observation of goal-directed actions and during observation of hand movements. Furthermore, no significant correlations between mu suppression on one hand and quality of imitation, age, and social communication questionnaire scores on the other hand were found. These findings challenge the "broken mirror" hypothesis of ASD, suggesting that impaired neural mirroring is not a distinctive feature of ASD., (© 2014 International Society for Autism Research, Wiley Periodicals, Inc.)

Time estimation of short durations (under 1 sec) was examined in low-functioning individuals with autism spectrum disorder (ASD) and typically developing (TD) children matched on mental age. Temporal bisection and generalization tasks were used to examine basic perceptual timing mechanisms. For both tasks, the participants with ASD demonstrated less sensitivity to variability in short durations than the TD children, adding to a growing body of literature suggesting deficits in timing exist for longer durations. The results highlight the need to examine multiple levels of processing of time-related information from basic perceptual mechanisms to higher level cognitive mechanisms., (© 2014 International Society for Autism Research, Wiley Periodicals, Inc.)

Visual-spatial strengths observed among people with autism spectrum disorder (ASD) may be associated with increased efficiency of selective attention mechanisms such as visual search. In a series of studies, researchers examined the visual search of targets that share features with distractors in a visual array and concluded that people with ASD showed enhanced performance on visual search tasks. However, methodological limitations, the small sample sizes, and the lack of developmental analysis have tempered the interpretations of these results. In this study, we specifically addressed age-related changes in visual search. We examined conjunctive visual search in groups of children with (n = 34) and without ASD (n = 35) at 7-9 years of age when visual search performance is beginning to improve, and later, at 10-12 years, when performance has improved. The results were consistent with previous developmental findings; 10- to 12-year-old children were significantly faster visual searchers than their 7- to 9-year-old counterparts. However, we found no evidence of enhanced search performance among the children with ASD at either the younger or older ages. More research is needed to understand the development of visual search in both children with and without ASD., (© 2014 International Society for Autism Research, Wiley Periodicals, Inc.)

CD38 encodes a ligand in the oxytocin signaling pathway. Some single nucleotide polymorphisms in this gene have been associated with low serum oxytocin levels in autism spectrum disorder (ASD) patients. Oxytocin disruption has been hypothesized to account for features of ASD, including impaired communication and social behavior, based on animal studies. Recent human studies have shown administration of oxytocin improving emotion recognition, promoting social behavior, and improving auditory processing of social stimuli in ASD patients. In addition to its role in oxytocin signaling, CD38 is involved in the regulation of calcium concentration in airway smooth muscle with impairment of CD38 being implicated in airway diseases like asthma. While a number of studies have implicated rare chromosomal deletions and duplications in helping determine genetic risk for autism, there are to our knowledge no reports describing rearrangements involving CD38 or deletions in patients with ASD. Here, we present two sisters diagnosed with autism and with features of regression-previously acquired speech lost in the second year of life. The younger sister, who also had asthma, inherited a maternal deletion of 4p15.32 that results in a BST1-CD38 fusion transcript. Their mother's deletion was mosaic and she was not affected. Although further work is required to assess functional consequences of the fusion transcript, we hypothesize that the proband's deletion may have served as a risk factor for autism that, when combined with other susceptibility variants, resulted in a more severe presentation than her sister., (© 2014 International Society for Autism Research, Wiley Periodicals, Inc.)

This study follows 40 children who were participants in a randomized controlled early intervention trial (Kasari et al.) from early childhood (2-5 years of age) to elementary school age (8-10 years). To fully utilize the available longitudinal data, the general linear mixed model was the primary analytical approach. The growth trajectories of joint attention skills (pointing, coordinated joint looking, and showing) and expressive language outcomes in these children were estimated based on five time points during the measurement period. The children were grouped by diagnosis at the last follow-up (autism, autism spectrum disorder (ASD), no diagnosis) and by their original treatment group assignment (joint attention, symbolic play, control), and differences between these groups were evaluated. Results showed that joint attention skills of coordinated joint looking and showing increased over time, and pointing to share interest increased over the first year measured and decreased thereafter. These trajectories were influenced by both original treatment assignment and diagnostic status at follow-up. In addition, a cross-lagged panel analysis revealed a causal relationship between early pointing and later language development. This study highlights the longitudinal and developmental importance of measures of early core deficits in autism, and suggests that both treatment and ASD symptomatology may influence growth in these skills over time., (© 2014 International Society for Autism Research, Wiley Periodicals, Inc.)

The present study aims to investigate the perception and production of several domains of prosodic performance in a cross-sectional sample of preadolescents and adolescents with and without high-functioning autism (HFA). To look at the role of language abilities on prosodic performance, the HFA groups were subdivided based on "high" and "low" language performance on the Clinical Evaluation of Language Fundamentals-Fourth Edition (CELF-4) (Semel, Wiig, & Secord). Social and cognitive abilities were also examined to determine their relationship to prosodic performance. No significant differences were seen in prosody scores in the younger versus older subgroups in typically developing (TD) group with age-appropriate language. There was small but significant improvement in performance with age in the groups with HFA. Comparing performance at each age level across diagnostic groups showed that preteens with HFA and higher language levels perform similarly to their TD peers on all prosodic tasks, whereas those with lower language skills scored significantly worse than both their higher language and TD peers when looking at composite perception and production findings. Teens with HFA showed no deficits on perception tasks; however, those with low language levels had difficulty on several production tasks when compared to the TD group. Regression analyses suggested that, for the preteen group with HFA, language was the strongest predictor of prosodic perception, whereas nonverbal IQ was most highly predictive of prosodic production. For adolescents with HFA, social skills significantly contributed to the prediction of prosodic perception and, along with language abilities, predicted prosodic production. Implications of these findings will be discussed., (© 2014 International Society for Autism Research, Wiley Periodicals, Inc.)

While high levels of anxiety and depression are now recognized as major co-occurring problems in children and young people with an autism spectrum disorder (ASD), research examining possible associations with individual differences in neurocognitive functioning has been limited. This study included 90 adolescents with an ASD aged 14-16 years with a full-scale IQ > 50. Using structural equation modeling, we examined the independent relationships between multiple measures of executive functioning and social cognition on severity of anxiety or depressive symptoms. Results indicated a significant association between poorer executive functioning and higher levels of anxiety, but not depression. In contrast, social cognition ability was not associated with either anxiety or depression. This study is the first to report significant associations between executive functions and anxiety in ASD. This may suggest that poor executive functioning is one factor associated with the high prevalence of anxiety disorder in children and adolescents with ASD., (© 2014 International Society for Autism Research, Wiley Periodicals, Inc.)

Impaired social functioning is a hallmark feature of autism spectrum disorder (ASD), often requiring treatment throughout the life span. PEERS(®) (Program for the Education and Enrichment of Relational Skills) is a parent-assisted social skills training for teens with ASD. Although PEERS(®) has an established evidence base in improving the social skills of adolescents and young adults with ASD in North America, the efficacy of this treatment has yet to be established in cross-cultural validation trials. The objective of this study is to examine the feasibility and treatment efficacy of a Korean version of PEERS(®) for enhancing social skills through a randomized controlled trial (RCT).The English version of the PEERS(®) Treatment Manual (Laugeson & Frankel, 2010) was translated into Korean and reviewed by 21 child mental health professionals. Items identified as culturally sensitive were surveyed by 447 middle school students, and material was modified accordingly. Participants included 47 teens between 12 and 18 years of age with a diagnosis of ASD and a verbal intelligence quotient (IQ) ≥ 65. Eligible teens were randomly assigned to a treatment group (TG) or delayed treatment control group (CG). Primary outcome measures included questionnaires and direct observations quantifying social ability and problems directly related to ASD. Secondary outcome measures included scales for depressive symptoms, anxiety, and other behavioral problems. Rating scales for parental depressive symptoms and anxiety were examined to detect changes in parental psychosocial functioning throughout the PEERS(®) treatment. Independent samples t-tests revealed no significant differences at baseline across the TG and CG conditions with regard to age (14.04 ± 1.64 and 13.54 ± 1.50 years), IQ (99.39 ± 18.09 & 100.67 ± 16.97), parental education, socioeconomic status, or ASD symptoms (p < 0.05), respectively. Results for treatment outcome suggest that the TG showed significant improvement in communication and social interaction domain scores on the Autism Diagnostic Observation Schedule, interpersonal relationship and play/leisure time on the subdomain scores of the Korean version of the Vineland Adaptive Behavior Scale (p's < 0.01), social skills knowledge total scores on the Test of Adolescent Social Skills Knowledge-Revised (p < 0.01), and decreased depressive symptoms on the Child Depression Inventory following treatment (p < 0.05). Analyses of parental outcome reveal a significant decrease in maternal state anxiety in the TG after controlling for potential confounding variables (p < 0.05). Despite cultural and linguistic differences, the PEERS(®) social skills intervention appears to be efficacious for teens with ASD in Korea with modest cultural adjustment. In an RCT, participants receiving the PEERS(®) treatment showed significant improvement in social skills knowledge, interpersonal skills, and play/leisure skills, as well as a decrease in depressive symptoms and ASD symptoms. This study represents one of only a few cross-cultural validation trials of an established evidence-based treatment for adolescents with ASD., (© 2014 International Society for Autism Research, Wiley Periodicals, Inc.)

Individuals with autism spectrum disorder (ASD) are known to process faces atypically. However, there has been considerable controversy regarding whether ASD individuals also scan faces differently from typical adults. Here we compared ASD individuals' face-scanning patterns with those of typically developing (TD) controls and intellectually disabled (ID) but non-ASD individuals with the use of an eye tracker and multiple approaches to analyze eye-tracking data. First, we analyzed the eye movement data with a traditional approach, measuring fixation duration on each area of interest within the face. We found that compared with TD and ID individuals, ASD individuals looked significantly shorter at the right eye. Second, we used a data-driven method that analyzes fixations on each pixel of the face stimulus and found that individuals with ASD looked more at the central nasal area than TD and ID individuals. Third, we used a novel saccade path analysis that measures frequencies of saccades between major face areas. We found that ASD individuals scanned less often between core facial features than TD individuals but did not differ from ID individuals. Findings from the multi-method approaches show that individuals with ASD appear not to have a pervasive ASD-specific atypicality in visual attention toward the face. The ASD-specific atypical face-scanning patterns were shown to be limited to fixations on the eyes and nose., (© 2013 International Society for Autism Research, Wiley Periodicals, Inc.)

Given the variability seen in Autism Spectrum Disorder (ASD), accurate quantification of functioning is vital to studying outcome and quality of life in affected individuals. The International Classification of Functioning, Disability and Health (ICF) provides a comprehensive, universally accepted framework for the description of health-related functioning. ICF Core Sets are shortlists of ICF categories that are selected to capture those aspects of functioning that are most relevant when describing a person with a specific condition. In this paper, the authors preview the process for developing ICF Core Sets for ASD, a collaboration with the World Health Organization and the ICF Research Branch. The ICF Children and Youth version (ICF-CY) was derived from the ICF and designed to capture the specific situation of the developing child. As ASD affects individuals throughout the life span, and the ICF-CY includes all ICF categories, the ICF-CY will be used in this project ("ICF(-CY)" from now on). The ICF(-CY) categories to be included in the ICF Core Sets for ASD will be determined at an ICF Core Set Consensus Conference, where evidence from four preparatory studies (a systematic review, an expert survey, a patient and caregiver qualitative study, and a clinical cross-sectional study) will be integrated. Comprehensive and Brief ICF Core Sets for ASD will be developed with the goal of providing useful standards for research and clinical practice and generating a common language for functioning and impairment in ASD in different areas of life and across the life span., (© 2013 International Society for Autism Research, Wiley Periodicals, Inc.)

Autism is usually defined by impairments in the social domain but has also been linked to deficient dorsal visual stream processing. However, inconsistent findings make the nature of this relationship unclear and thus, we examined the role of stimulus-driven transient attention, presumably activated by the dorsal stream in autistic tendency. Contrast thresholds for object discrimination were compared between groups with high and low self-rated autistic tendency utilizing the socially based Autism Spectrum Quotient (AQ). Visual stimuli were presented with either abrupt or with ramped contrast onsets/offsets in order to manipulate the demands of transient attention. Larger impairments in performance of abrupt compared with ramped object presentation were established in the high AQ group. Furthermore, self-reported social skills predicted abrupt task performance, suggesting an important visual perception deficiency in autism-related traits. Autism spectrum disorder may be associated with reduced utilization of the dorsal stream to rapidly activate attention prior to ventral stream processing when stimuli are transient., (© 2013 International Society for Autism Research, Wiley Periodicals, Inc.)

While temporal and perceptual processing abnormalities, identified in a number of electrophysiological and brain imaging studies of individuals with (ASD), are likely to impact on speech perception, surprisingly little is known about the behavioral outcomes of such abnormalities. It has been hypothesized that rapid temporal processing deficits may be linked to impaired language development through interference with acoustic information during speech perception. The present study aimed to investigate the impact of temporal changes on encoding and recall of speech, and the associated cognitive, clinical, and behavioral correlates in adults with ASD. Research carried out with typically developing (TD) adults has shown that word recall diminishes as the speed of speech increases, and it was predicted that the magnitude of this effect would be far greater in those with ASD because of a preexisting rapid temporal processing deficit. Nineteen high-functioning adults with ASD, and age- and intelligence-matched TD controls performed verbatim recall of temporally manipulated sentences. Reduced levels of word recall in response to increases in presentation speed were observed, and this effect was greater in the older participants in the ASD group than in the control group. This is the first study to show that both sensory abnormalities and aging impact on speech encoding in ASD. Auditory processing deficits in ASD may be indicative of an association with the sensory abnormalities and social and communication impairments characterizing the disorder., (© 2013 International Society for Autism Research, Wiley Periodicals, Inc.)

Children with autism may have difficulties in audiovisual speech perception, which has been linked to speech perception and language development. However, little has been done to examine children with Asperger syndrome as a group on tasks assessing audiovisual speech perception, despite this group's often greater language skills. Samples of children with autism, Asperger syndrome, and Down syndrome, as well as a typically developing sample, were presented with an auditory-only condition, a speech-reading condition, and an audiovisual condition designed to elicit the McGurk effect. Children with autism demonstrated unimodal performance at the same level as the other groups, yet showed a lower rate of the McGurk effect compared with the Asperger, Down and typical samples. These results suggest that children with autism may have unique intermodal speech perception difficulties linked to their representations of speech sounds., (© 2013 International Society for Autism Research, Wiley Periodicals, Inc.)

Can adults with autism spectrum disorders (ASD) infer what happened to someone from their emotional response? Millikan has argued that in everyday life, others' emotions are most commonly used to work out the antecedents of behavior, an ability termed retrodictive mindreading. As those with ASD show difficulties interpreting others' emotions, we predicted that these individuals would have difficulty with retrodictive mindreading. Sixteen adults with high-functioning autism or Asperger's syndrome and 19 typically developing adults viewed 21 video clips of people reacting to one of three gifts (chocolate, monopoly money, or a homemade novelty) and then inferred what gift the recipient received and the emotion expressed by that person. Participants' eye movements were recorded while they viewed the videos. Results showed that participants with ASD were only less accurate when inferring who received a chocolate or homemade gift. This difficulty was not due to lack of understanding what emotions were appropriate in response to each gift, as both groups gave consistent gift and emotion inferences significantly above chance (genuine positive for chocolate and feigned positive for homemade). Those with ASD did not look significantly less to the eyes of faces in the videos, and looking to the eyes did not correlate with accuracy on the task. These results suggest that those with ASD are less accurate when retrodicting events involving recognition of genuine and feigned positive emotions, and challenge claims that lack of attention to the eyes causes emotion recognition difficulties in ASD., (© 2013 International Society for Autism Research, Wiley Periodicals, Inc.)

Oxidative stress is suspected to be one of the several contributing factors in the etiology of autism spectrum disorder (ASD). We analyzed genes of the superoxide dismutase family (SOD1, SOD2, and SOD3) that are part of a major antioxidative stress system in human in order to detect the genetic variants contributing to the development of ASD. Using the optimized high-resolution melting (HRM) analysis, we identified two rare single nucleotide polymorphisms (SNPs) associated with the etiology of ASD. Both are located in the superoxide dismutase 1 (SOD1) gene and have a minor allele frequency in healthy population ~5%. The SNP c.239 + 34A>C (rs2234694) and SNP g.3341C>G (rs36233090) were detected with an odds ratio of 2.65 and P < 0.01. Both are located in the noncoding potentially regulatory regions of the SOD1 gene. This adds to the importance of rare SNPs in the etiology of complex diseases as well as to the importance of noncoding genetic variants analysis with a potential influence on the regulation of gene expression., (© 2013 International Society for Autism Research, Wiley Periodicals, Inc.)

The present study examined how eye movements during scene viewing are modulated by adopting psychological perspectives in both adults with autism spectrum disorders (ASD) and typically developing adults. In the current study, participants viewed house scenes with either non-perspective-taking (look for valuable items/features of the house that need fixing) or perspective-taking instructions (imagine that you are a burglar/repairman) while their eye movements were recorded. The eye movement measures revealed that for the "look for the valuable items" and burglar perspective task, the ASD group showed typical relevance effects (the preference to look at schema-relevant compared with schema-irrelevant targets) in their eye movements. However, we found subtle processing differences between the groups that were related to initial orienting to and processing of schema-relevant items for the "look for the features that need fixing" and the repairman perspective-taking task. There was an absence of a relevance effect for the ASD group for the repairman perspective and its non-perspective-taking equivalent instruction showing that the identification of items relevant to those schemas was more difficult for the ASD group. The present findings suggest that resolving ambiguity may be a defining feature of complex information processing deficits in ASD., (© 2013 International Society for Autism Research, Wiley Periodicals, Inc.)

Social Emotional NeuroScience Endocrinology Theatre is a novel intervention program aimed at improving reciprocal social interaction in youth with autism spectrum disorder (ASD) using behavioral strategies and theatrical techniques in a peer-mediated model. Previous research using a 3-month model showed improvement in face perception, social interaction, and reductions in stress. The current study assessed a 2-week summer camp model. Typically developing peers were trained and paired with ASD youth (8-17 years). Social perception and interaction skills were measured before and after treatment using neuropsychological and parental measures. Behavioral coding by reliable, independent raters was conducted within the treatment context (theatre) and outside the setting (playground). Salivary cortisol levels to assess physiological arousal were measured across contexts (home, theatre, and playground). A pretest-posttest design for within-group comparisons was used, and prespecified pairwise comparisons were achieved using a nonparametric Wilcoxon signed-rank test. Significant differences were observed in face processing, social awareness, and social cognition (P < 0.05). Duration of interaction with familiar peers increased significantly over the course of treatment (P < 0.05), while engagement with novel peers outside the treatment setting remained stable. Cortisol levels rose on the first day of camp compared with home values yet declined by the end of treatment and further reduced during posttreatment play with peers. Results corroborate previous findings that the peer-mediated theatre program contributes to improvement in core social deficits in ASD using a short-term, summer camp treatment model. Future studies will explore treatment length and peer familiarity to optimize and generalize gains., (© 2013 International Society for Autism Research, Wiley Periodicals, Inc.)

It has been suggested that autism-specific imitative deficits may be reduced or even spared in object-related activities. However, most previous research has not sufficiently distinguished object movement reenactment (learning about the ways in which object move) from imitation (learning about the topography of demonstrated actions). Twenty children with autism (CWA) and 20 typically developing children (TDC) were presented with puzzle boxes containing prizes. Test objects and experimental conditions were designed to isolate object- and action-related aspects of demonstrations. There were four types of video demonstrations: (a) a full demonstration by an adult; (b) a ghost demonstration with object movements alone; (c) mimed solutions demonstrated adjacent to the objects; and (d) random actions performed on the surface of the objects. There were no significant between-group differences in the degree to which CWA and TDC matched the full demonstrations, the actual demonstrations or in their times to first solution in any of the conditions. Although there was no clear imitative deficit in the CWA, regression analyses were conducted to explore in more detail whether diagnosis, verbal intelligence quotient (VIQ), nonverbal IQ NVIQ, age or motor coordination predicted performance. The results are discussed in relation to the use of extrinsic vs. intrinsic rewards and the interplay between motor coordination and the relative rigidity vs. pliability of objects., (© 2013 International Society for Autism Research, Wiley Periodicals, Inc.)

The relation between autism spectrum disorders (ASD) and schizophrenia is a subject of intense debate and research due to evidence of common neurobiological pathways in the two disorders. The objective of this study was to explore whether deficits in prepulse inhibition (PPI) of the startle reflex, as usually seen in schizophrenic patients, can be replicated in a group of children with ASD in comparison with a group of matched neuro-typically developed (NTD) controls. An additional aim was to explore possible psychophysiological subgroups within our ASD sample. In a case-control design, 35 ASD patients and 40 matched NTD controls were tested in a psychophysiological test battery. The PPI of the acoustic startle reflex was analyzed in 18 ASD subjects and 34 NTD controls. Habituation and sensitization were analyzed in 23 ASD subjects and 39 NTD controls. In trials with less intense prestimuli (76 dB), patients with ASD did not display the drop in percentage PPI normally found in healthy controls. In addition, ASD patients showed significantly increased sensitization compared with NTD controls. Combined, our results may reflect the hypersensitivity to sensory information in children with ASD. The relation to PPI deficits observed in schizophrenia is not apparent. Future research should study the developmental course of PPI deficits in ASD patients in a longitudinal design., (© 2013 International Society for Autism Research, Wiley Periodicals, Inc.)

It remains unclear why individuals with autism spectrum disorder (ASD) tend to respond in an atypical manner in social situations. Investigating autonomic and subjective responses to social vs. nonsocial stimuli may help to reveal underlying mechanisms of these atypical responses. This study examined autonomic responses (skin conductance level and heart rate) and subjective responses to social vs. nonsocial pictures in 37 adolescents with an ASD and 36 typically developing (TD) adolescents. Thirty-six pictures from the International Affective Picture System were presented, divided into six categories based on social content (social vs. nonsocial) and pleasantness (pleasant, neutral, and unpleasant). Both in adolescents with ASD as well as TD adolescents, pictures with a social content resulted in higher skin conductance responses (SCRs) for pleasant and unpleasant pictures than for neutral pictures. No differences in SCRs were found for the three nonsocial picture categories. Unpleasant pictures, both with and without a social content, showed more heart rate deceleration than neutral pictures. Self-reported arousal ratings were influenced by the social and affective content of a picture. No differences were found between individuals with ASD and TD individuals in their autonomic and subjective responses to the picture categories. These results suggest that adolescents with ASD do not show atypical autonomic or subjective responses to pictures with and without a social content. These findings make it less likely that impairments in social information processing in individuals with ASD can be explained by atypical autonomic responses to social stimuli., (© 2013 International Society for Autism Research, Wiley Periodicals, Inc.)

Relationships between parental broader autism phenotype (BAP) scores, gender, selective serotonin reuptake inhibitor (SSRI) treatment, serotonin (5HT) levels, and the child's symptoms were investigated in a family study of autism spectrum disorder (ASD). The Broader Autism Phenotype Questionnaire (BAPQ) was used to measure the BAP of 275 parents. Fathers not taking SSRIs (F-SSRI; n = 115) scored significantly higher on BAP Total and Aloof subscales compared to mothers not receiving treatment (M-SSRI; n = 136.) However, mothers taking SSRIs (M + SSRI; n = 19) scored higher than those not taking medication on BAP Total and Rigid subscales, and they were more likely to be BAPQ Total, Aloof, and Rigid positive. Significant correlations were noted between proband autism symptoms and parental BAPQ scores such that Total, Aloof, and Rigid subscale scores of F-SSRI correlated with proband restricted repetitive behavior (RRB) measures on the ADOS, CRI, and RBS-R. However, only the Aloof subscale score of M + SSRI correlated with proband RRB on the ADOS. The correlation between the BAPQ scores of mothers taking SSRIs and child scores, as well as the increase in BAPQ scores of this group of mothers, requires careful interpretation and further study because correlations would not withstand multiple corrections. As expected by previous research, significant parent-child correlations were observed for 5HT levels. However, 5HT levels were not correlated with behavioral measures. Study results suggest that the expression of the BAP varies not only across parental gender, but also across individuals using psychotropic medication and those who do not., (© 2013 International Society for Autism Research, Wiley Periodicals, Inc.)

This paper addresses the issue of assessing communication, language, and associated cognitive and behavioral abilities of minimally verbal children with autism spectrum disorder (ASD), presenting a summary of a year-long series of meetings held by a group of experts in the field of ASD and National Institutes of Health staff. In this paper, our goals were to first define the population and then present general guidelines for optimizing assessment sessions for this challenging population. We then summarize the available measures that can be used across a variety of behavioral domains that are most directly relevant to developing language skills, including oral motor skills, vocal repertoire, receptive and expressive language, imitation, intentional communication, play, social behavior, repetitive and sensory behaviors, and nonverbal cognition. We conclude with a discussion of some of the limitations in the available measures and highlight recommendations for future research in this area., (© 2013 International Society for Autism Research, Wiley Periodicals, Inc.)

Autism and its related disorders are commonly described as lying along a continuum that ranges in severity and are collectively referred to as autism spectrum disorders (ASDs). Although all individuals with ASD meet the social impairment diagnostic criteria outlined in the DSM-IV-TR, they do not present with the same social difficulties. The variability in the expression and severity of social competence is particularly evident among the group of individuals with "high-functioning" ASD who appear to have difficulty applying their average to above average intelligence in a social context. There is a striking paucity of empirical research investigating individual differences in social functioning among individuals with high-functioning ASD. It is possible that more detailed investigations of social competence have been impeded by the lack of standardized measures available to assess the nature and severity of social impairment. The aim of the current study was to develop and evaluate a parent rating scale capable of assessing individual differences in social competence (i.e. strengths and challenges) among adolescents with ASD: the Multidimensional Social Competence Scale (MSCS). Results from confirmatory factor analyses supported the hypothesized multidimensional factor structure of the MSCS. Seven relatively distinct domains of social competence were identified including social motivation, social inferencing, demonstrating empathic concern, social knowledge, verbal conversation skills, nonverbal sending skills, and emotion regulation. Psychometric evidence provided preliminary support for the reliability and validity of the scale. Possible applications of this promising new parent rating scale in both research and clinical settings are discussed., (© 2013 International Society for Autism Research, Wiley Periodicals, Inc.)

Previous studies have shown reduced empathic responsiveness to others' emotions in preschoolers with autism spectrum disorder (ASD) and an intellectual disability. However, age and intelligence may promote children's empathic responsiveness. Therefore, we examined the empathic responsiveness in normally intelligent school-aged children and adolescents with a clinical diagnosis of ASD (n = 151) and in a typically developing comparison group (n = 50), using structured observations and parent reports. Based on the observations, participants' responses to the emotional displays of an interviewer were surprisingly similar. However, compared with parents from the comparison group, parents of a child with ASD reported significantly fewer empathic responses, particularly when the child received a high score on the Autism Diagnostic Observation Schedule. Even though parents report a reduced empathic responsiveness in school-aged children and adolescents with ASD, it may be difficult to find these empathic limitations during brief observations in a structured setting., (© 2013 International Society for Autism Research, Wiley Periodicals, Inc.)

Many children with autism spectrum disorders (ASD) demonstrate deficits in language comprehension, but little is known about how they process spoken language as it unfolds. Real-time lexical comprehension is associated with language and cognition in children without ASD, suggesting that this may also be the case for children with ASD. This study adopted an individual differences approach to characterizing real-time comprehension of familiar words in a group of 34 three- to six-year-olds with ASD. The looking-while-listening paradigm was employed; it measures online accuracy and latency through language-mediated eye movements and has limited task demands. On average, children demonstrated comprehension of the familiar words, but considerable variability emerged. Children with better accuracy were faster to process the familiar words. In combination, processing speed and comprehension on a standardized language assessment explained 63% of the variance in online accuracy. Online accuracy was not correlated with autism severity or maternal education, and nonverbal cognition did not explain unique variance. Notably, online accuracy at age 5½ was related to vocabulary comprehension 3 years earlier. The words typically learned earliest in life were processed most quickly. Consistent with a dimensional view of language abilities, these findings point to similarities in patterns of language acquisition in typically developing children and those with ASD. Overall, our results emphasize the value of examining individual differences in real-time language comprehension in this population. We propose that the looking-while-listening paradigm is a sensitive and valuable methodological tool that can be applied across many areas of autism research., (© 2013 International Society for Autism Research, Wiley Periodicals, Inc.)

Autism is a developmental disorder characterized, in part, by sensory abnormalities. It is well established that most if not all patients with autism have problems with auditory processing, ranging from deafness to hyperacusis, and physiological testing of auditory function (i.e. auditory brain stem responses) implicates brain stem dysfunction in autism. Additionally, previous research from this lab has revealed significantly fewer auditory brain stem neurons in autistic subjects as young as 2 years of age. These observations have led us to hypothesize that objective, noninvasive measures of auditory function can be used as an early screening tool to identify neonates with an elevated risk of carrying a diagnosis of autism. Here, we provide a detailed quantitative investigation of the acoustic stapedial reflex (ASR), a three- or four-neuron brain stem circuit, in young autistic subjects and normal developing controls. Indeed, we find significantly lower thresholds, responses occurring at significantly longer latency and right-left asymmetry in autistic subjects. The results from this investigation support deficits in auditory function as a cardinal feature of autism and suggest that individuals with autism can be identified by their ASR responses., (© 2013 International Society for Autism Research, Wiley Periodicals, Inc.)

Previous research has reported that autistic adults do not manage their reputation, purportedly due to problems with theory of mind [Izuma, Matsumoto, Camerer, & Adolphs]. The current study aimed to test alternative explanations for this apparent lack of reputation management. Twenty typical and 19 autistic adults donated to charity and to a person, both when alone and when observed. In an additional manipulation, for half of the participants, the observer was also the recipient of their donations, and participants were told that this observer would subsequently have the opportunity to donate to them (motivation condition). This manipulation was designed to encourage an expectation of a reciprocal "tit-for-tat" strategy in the participant, which may motivate participants to change their behavior to receive more donations. The remaining participants were told that the person watching was just observing the procedure (no motivation condition). Our results replicated Izuma et al.'s finding that autistic adults did not donate more to charity when observed. Yet, in the motivation condition, both typical and autistic adults donated significantly more to the observer when watched, although this effect was significantly attenuated in autistic individuals. Results indicate that, while individuals with autism may have the ability to think about reputation, a reduced expectation of reciprocal behavior from others may reduce the degree to which they engage in reputation management., (© 2013 International Society for Autism Research, Wiley Periodicals, Inc.)

Impairments in social attention play a major role in autism, but little is known about their role in development after preschool. In this study, a public speaking task was used to study social attention, its moderators, and its association with classroom learning in elementary and secondary students with higher functioning autism spectrum disorder (HFASD). Thirty-seven students with HFASD and 54 age- and intelligence quotient (IQ)-matched peers without symptoms of ASD were assessed in a virtual classroom public speaking paradigm. This paradigm assessed the ability to attend to nine avatar peers seated at a table, while simultaneously answering self-referenced questions. Students with HFASD looked less frequently to avatar peers in the classroom while talking. However, social attention was moderated in the HFASD sample such that students with lower IQ, and/or more symptoms of social anxiety, and/or more attention deficit/hyperactivity disorder inattentive symptoms, displayed more atypical social attention. Group differences were more pronounced when the classroom contained social avatars versus nonsocial targets. Moreover, measures of social attention rather than nonsocial attention were significantly associated with parent report and objective measures of learning in the classroom. The data in this study support the hypothesis of the Social Attention Model of ASD that social attention disturbance remains part of the school-aged phenotype of autism that is related to syndrome-specific problems in social learning. More research of this kind would likely contribute to advances in the understanding of the development of the spectrum of autism and educational intervention approaches for affected school-aged children., (© 2013 International Society for Autism Research, Wiley Periodicals, Inc.)

We assessed whether autistic traits are related to the ability to identify flavour. In general, the colour of the food or drink facilitates identification of its flavour. In the current study, the colour of drinks either provided congruent, incongruent or ambiguous (colourless) information about the flavour. Participants identified the flavours of 12 drinks from a list and completed a measure of autistic traits, the Autism-Spectrum Quotient (AQ). In line with previous studies, flavour identification was impaired in incongruent conditions, while identification in congruent conditions was not improved when compared with that in ambiguous conditions. AQ scores were related to flavour identification in incongruent conditions, in that as the AQ score increased, accuracy of flavour identification decreased. There were no relationships found in the congruent or ambiguous conditions. This finding is in line with the idea that conflicting sensory information may be more disruptive for individuals on the autism spectrum., (© 2013 International Society for Autism Research, Wiley Periodicals, Inc.)

It has been suggested that atypical amygdala function contributes to the social impairments characteristic of autism spectrum disorders (ASDs). Previous research has demonstrated that adolescents and adults with ASD generate normal response during a fear-potentiated startle paradigm, suggesting this aspect of amygdala function is intact and may not account for the social dysfunction associated with the condition. The amygdala also plays a crucial role in the expression of anxiety and may contribute to high rates of reported anxiety in individuals with ASD. The present study partially replicates prior work by examining the fear-potentiated startle response in adolescents with ASD, and extends this to investigate the relationship between startle response and anxiety. Eyeblink magnitude and latency (electromyographic activity; EMG) were collected from 20 adolescents with ASD and 19 typically developing (TD) age-matched adolescents during a fear-potentiated startle paradigm. Parent-report and self-report of anxiety and additional psychiatric symptoms were collected. Parental reports indicated higher rates of associated psychopathology in adolescents with ASD compared with TD adolescents. Consistent with previous results, both groups showed normal potentiated startle response, and no group differences in EMG were found. Symptoms of anxiety and level of social impairment were unrelated to startle response. These findings held for all levels of anxiety, suggesting that within the context of the fear-potentiated startle paradigm, amygdala response is not associated with degree of atypical social or emotional functioning in ASD., (© 2013 International Society for Autism Research, Wiley Periodicals, Inc.)

Research indicates a positive relation between the sibling constellation and theory of mind (ToM) development in typically developing (TD) children. Less is known about this association in children with autism spectrum disorder (ASD). The current study examined the association among the presence and number of siblings, birth order, and false belief (FB) understanding in children with ASD and a TD comparison group. Two FB tasks (change of contents and change of location) and the Peabody Picture Vocabulary Test were administered to 57 children with ASD and 28 TD children during a home visit. One parent of each child reported on demographics and the sibling constellation. Separate hierarchical regressions controlled for age, receptive language ability, and scores on the Social Communication Questionnaire. In children with ASD, no association was observed between presence or number of siblings and ToM. However, the presence of older (but not younger) siblings was found to be positively associated with ToM. Children with ASD who had at least one older sibling performed similarly to the TD group, whereas children with ASD who had no older siblings performed significantly worse than the TD group. These findings indicate an advantage for FB performance in children with ASD who have an older sibling. They may bear on decisions to include older siblings or peers in intervention programs and may also contribute to a more complete understanding of the origins of individual differences in ToM ability in children with ASD., (© 2013 International Society for Autism Research, Wiley Periodicals, Inc.)

We report on an automatic technique for quantifying two types of repetitive speech: repetitions of what the child says him/herself (self-repeats) and of what is uttered by an interlocutor (echolalia). We apply this technique to a sample of 111 children between the ages of four and eight: 42 typically developing children (TD), 19 children with specific language impairment (SLI), 25 children with autism spectrum disorders (ASD) plus language impairment (ALI), and 25 children with ASD with normal, non-impaired language (ALN). The results indicate robust differences in echolalia between the TD and ASD groups as a whole (ALN + ALI), and between TD and ALN children. There were no significant differences between ALI and SLI children for echolalia or self-repetitions. The results confirm previous findings that children with ASD repeat the language of others more than other populations of children. On the other hand, self-repetition does not appear to be significantly more frequent in ASD, nor does it matter whether the child's echolalia occurred within one (immediate) or two turns (near-immediate) of the adult's original utterance. Furthermore, non-significant differences between ALN and SLI, between TD and SLI, and between ALI and TD are suggestive that echolalia may not be specific to ALN or to ASD in general. One important innovation of this work is an objective fully automatic technique for assessing the amount of repetition in a transcript of a child's utterances., (© 2013 International Society for Autism Research, Wiley Periodicals, Inc.)

Autism spectrum disorders (ASDs) are associated with a marked disturbance of neural functional connectivity, which may arise from disrupted organization of white matter. The aim of this study was to use constrained spherical deconvolution (CSD)-based tractography to isolate and characterize major intrahemispheric white matter tracts that are important in visuospatial processing. CSD-based tractography avoids a number of critical confounds that are associated with diffusion tensor tractography, and to our knowledge, this is the first time that this advanced diffusion tractography method has been used in autism research. Twenty-five participants with ASD and aged 25, intelligence quotient-matched controls completed a high angular resolution diffusion imaging scan. The inferior fronto-occipital fasciculus (IFOF) and arcuate fasciculus were isolated using CSD-based tractography. Quantitative diffusion measures of white matter microstructural organization were compared between groups and associated with visuospatial processing performance. Significant alteration of white matter organization was present in the right IFOF in individuals with ASD. In addition, poorer visuospatial processing was associated in individuals with ASD with disrupted white matter in the right IFOF. Using a novel, advanced tractography method to isolate major intrahemispheric white matter tracts in autism, this research has demonstrated that there are significant alterations in the microstructural organization of white matter in the right IFOF in ASD. This alteration was associated with poorer visuospatial processing performance in the ASD group. This study provides an insight into structural brain abnormalities that may influence atypical visuospatial processing in autism., (© 2013 International Society for Autism Research, Wiley Periodicals, Inc.)

The ability to recognize when one is being imitated has been hypothesized to be an important developmental process related to the emergence of more advanced social-cognitive skills. While a series of behaviors indicating progressively more mature imitation recognition (IR) skills has been assessed in typically developing children, empirical work with children with autism spectrum disorders (ASDs) has largely focused on basic social responses to an imitative adult (e.g. increases in eye contact). Limited work has explored more mature IR behaviors in this population. This study compared the degree to which children with ASD engage in different behaviors thought to be indicative of IR during a naturalistic imitation task and the relationship between different types of IR behaviors and social-cognitive skills (i.e. imitation, language, social reciprocity, and joint attention). Thirty children with ASD were administered standardized measures of cognitive level, language, joint attention, social reciprocity, and imitation. IR behaviors were observed during periods of contingent imitation by an adult. Participants engaged more frequently in less mature (e.g. looking at the experimenter's toy or face) than more mature IR behaviors (e.g. testing the experimenter's intent to imitate). After controlling for developmental level, social reciprocity, object imitation, and gesture imitation were positively correlated with more mature IR. These findings suggest that the development of more mature IR skills is related to the development of other social-cognitive skills in children with ASD and provide additional empirical support for reports of more mature IR observed in this population. , Inc., (© 2013 International Society for Autism Research, Wiley Periodicals, Inc.)

Diagnosis of an autism spectrum disorder (ASD) requires a qualitative assessment of social aptitude: one person judging whether another person interacts in a "typical" way. We hypothesized that mice could be used to make a similar judgment if they prefer "typical" over "atypical" social interactions with mouse models relevant to ASD. We used wild-type C57BL/6 (B6) mice as "judges" and evaluated their preference for a chamber containing a "typical" (B6 or 129S6) or an "atypical" mouse. For our atypical mouse stimuli, we chose two inbred strains with well-documented social phenotypes (BTBR and BALB/c), as well a mutant line with abnormal social behavior and seizures (Gabrb3 +/-). Overall, we observed a stimulus by time interaction (P < 0.0001), with B6 mice preferring the typical mouse chamber during the last 10 min of the 30-min test. For two of the individual stimulus pairings, we observed a similar chamber by time interaction (BALB/c vs. 129S6, P = 0.0007; Gabrb3 +/- vs. 129S6, P = 0.033). For the third stimulus pairing, we found a trend for preference of the typical mouse across time (BTBR vs. B6, P = 0.051). We repeated the experiments using 129S6 mice as judges and found a significant overall interaction (P = 0.034), but only one stimulus pairing reached significance on its own (BALB/c vs. 129S6, P = 0.0021). These data suggest that a characteristic pattern of exploration in B6 mice can distinguish some socially atypical animals from controls., (© 2013 International Society for Autism Research, Wiley Periodicals, Inc.)

This study examined differences in acoustic characteristics of infant cries in a sample of babies at risk for autism and a low-risk comparison group. Cry samples derived from vocal recordings of 6-month-old infants at risk for autism spectrum disorder (ASD; n = 21) and low-risk infants (n = 18) were subjected to acoustic analyses using analysis software designed for this purpose. Cries were categorized as either pain-related or non-pain-related based on videotape coding. At-risk infants produced pain-related cries with higher and more variable fundamental frequency (F (0) ) than low-risk infants. At-risk infants later classified with ASD at 36 months had among the highest F (0) values for both types of cries and produced cries that were more poorly phonated than those of nonautistic infants, reflecting cries that were less likely to be produced in a voiced mode. These results provide preliminary evidence that disruptions in cry acoustics may be part of an atypical vocal signature of autism in early life., (© 2012 International Society for Autism Research, Wiley Periodicals, Inc.)

In a developmentally delayed girl with an autism spectrum disorder, Single nucleotide polymorphism (SNP) array analysis showed a de novo 280 kb deletion on chromosome 16q23.2 involving two genes, GAN and CMIP. Inactivating mutations in GAN cause the autosomal recessive disorder giant axonal neuropathy, not present in our patient. CMIP was recently implicated in the etiology of specific language impairment by genome-wide association analysis. It modulates phonological short-term memory and hence plays an important role in language acquisition. Overlaps of specific language impairment and autism have been debated in the literature regarding the phenotypical language profile as well as etiology. Our patient illustrates that haploinsufficiency of CMIP may contribute to autism spectrum disorders. Our finding further supports the existence of a genetic overlap in the etiology of specific language impairment and autism., (© 2012 International Society for Autism Research, Wiley Periodicals, Inc.)

Prenatal testosterone (PT) effects have been proposed to increase systemizing (the drive to understand lawful input-output relationships), to decrease empathizing (the drive to understand others), and to cause autism via hypermasculinization of the brain. Digit ratio 2D:4D is a putative marker of PT effects in humans. An online study (n = 1896) into the relationship between the Reading the Mind in the Eyes Test (a widely used measure of empathizing) and self-measured 2D:4D in a nonclinical sample is reported. No evidence for a link between empathizing and 2D:4D in either females or males emerged. Further, three meta-analyses are presented that look into the relationships of 2D:4D with autism spectrum disorder (ASD), systemizing, and empathizing. 2D:4D was substantially lower (more masculine) in ASD-affected individuals than in normal controls (d = -0.58, P < 0.001). However, 2D:4D was found to be virtually unrelated to systemizing and empathizing in normal adults. The results support the idea that high PT is a risk factor for autism, but they challenge the view that PT substantially contributes to sex differences in systemizing and empathizing. Possibly, this pattern reflects an interaction effect, whereby PT drives ASD characteristic changes only in brains with a specific damage., (© 2012 International Society for Autism Research, Wiley Periodicals, Inc.)

Autism spectrum disorders (ASD) are associated with differences in sensory sensitivity and affective response to sensory stimuli, the neural basis of which is still largely unknown. We used psychophysics and functional magnetic resonance imaging (fMRI) to investigate responses to somatosensory stimulation with three textured surfaces that spanned a range of roughness and pleasantness in a sample of adults with ASD and a control group. While psychophysical ratings of roughness and pleasantness were largely similar across the two groups, the ASD group gave pleasant and unpleasant textures more extreme average ratings than did controls. In addition, their ratings for a neutral texture were more variable than controls, indicating they are less consistent in evaluating a stimulus that is affectively ambiguous. Changes in brain blood oxygenation level-dependent (BOLD) signal in response to stimulation with these textures differed substantially between the groups, with the ASD group exhibiting diminished responses compared to the control group, particularly for pleasant and neutral textures. For the most unpleasant texture, the ASD group exhibited greater BOLD response than controls in affective somatosensory processing areas such as the posterior cingulate cortex and the insula. The amplitude of response in the insula in response to the unpleasant texture was positively correlated with social impairment as measured by the Autism Diagnostic Interview-Revised (ADI-R). These results suggest that people with ASD tend to show diminished response to pleasant and neutral stimuli, and exaggerated limbic responses to unpleasant stimuli, which may contribute to diminished social reward associated with touch, perpetuating social withdrawal, and aberrant social development., (© 2012 International Society for Autism Research, Wiley Periodicals, Inc.)

Autism spectrum disorder (ASD) is a complex, neurodevelopmental disorder with various structural abnormalities for different patient groups. Because of the heterogeneity of the disorder, several biomarkers have been suggested so far. Here, we explore the potential of sulcal surface and length as biomarkers. Three-dimensional T1-weighted images of 15 adolescents of normal intelligence with ASD and 15 age-, sex-, and intelligence quotient-matched control adolescents were analysed using Brainvisa 4.0 (http://www.brainvisa.info), which automatically extracts the cortical folds and labels them as 59 sulcal pieces. For each sulcus, the surface, length, and mean geodesic depth were computed using morphometry analysis within this software package. General linear model was conducted to compare the estimated values for the two groups, ASD and control. In the ASD group, the left insula and the right intraparietal sulcus (IPS) had significantly higher values for surface and length, respectively. Nonetheless for all sulcal pieces, the mean geodesic depth was not significantly different between the two groups. Our results suggest that sulcal surface and length can have correlation with morphological changes of cortex in ASD. Greater surface area and length in insula and IPS, respectively, may reflect greater folding. This could result in greater separation of functions with an impact upon the integrative functions of these regions., (© 2012 International Society for Autism Research, Wiley Periodicals, Inc.)

Measurement of the severity of autism at a single time point, and over time, is a widespread challenge for researchers. Recently, Gotham, Pickles, and Lord published a severity metric (calibrated severity scores; CSS) that takes into account age and language level and is based on raw total scores of the Autism Diagnostic Observation Schedule (ADOS), a standardized measure commonly used in autism diagnosis. The present study examined psychometric characteristics of the CSS compared to raw scores in an independent sample of 368 children aged 2 to 12 years with autism, pervasive developmental disorder-not otherwise specified (PDD-NOS), non-spectrum delay, or typical development. Reflecting the intended calibration, the CSS were more uniformly distributed within clinical diagnostic category and across ADOS modules than were raw scores. Cross-sectional analyses examining raw and severity scores and their relationships to participant characteristics revealed that verbal developmental level was a significant predictor of raw score but accounted for significantly less variance in the CSS. Longitudinal analyses indicated overall stability of the CSS over 12 to 24 months in children with autism. Findings from this study support the use of the CSS as a more valid indicator of autism severity than the ADOS raw total score, and extend the literature by examining the stability over 12 to 24 months of the CSS in children with ASD., (© 2012 International Society for Autism Research, Wiley Periodicals, Inc.)

The study examined whether 9-month-old infants at average vs. high risk for autism spectrum disorder (ASD) process facial features (eyes, mouth) differently and whether such differences are related to infants' social and communicative skills. Eye tracking and visual event-related potentials (ERPs) were recorded in 35 infants (20 average-risk typical infants, 15 high-risk siblings of children with ASD) while they viewed photographs of a smiling unfamiliar female face. On 30% of the trials, the eyes or the mouth of that face was replaced with corresponding features from a different female. There were no group differences in the number, duration, or distribution of fixations, and all infants looked at the eyes and mouth regions equally. However, increased attention to the mouth was associated with weaker receptive communication skills and increased attention to the eyes correlated with better interpersonal skills. ERP results revealed that all infants detected eye and mouth changes but did so using different brain mechanisms. Changes in facial features were associated with changes in activity of the face perception mechanisms (N290) for the average-risk group but not for the high-risk infants. For all infants, correlations between ERP and eye-tracking measures indicated that larger and faster ERPs to feature changes were associated with fewer fixations on the irrelevant regions of stimuli. The size and latency of the ERP responses also correlated with parental reports of receptive and expressive communication skills, suggesting that differences in brain processing of human faces are associated with individual differences in social-communicative behaviors., (© 2012 International Society for Autism Research, Wiley Periodicals, Inc.)

The present study sought to test the global-identity and local-emotion processing hypothesis in face perception by examining emotional interference in face perception in children with high-functioning autism/Asperger's syndrome. Participants judged either the expression or the identity of faces while identity/expression was either held constant or varied (Garner paradigm). The results revealed that emotional expressions interfered with identity processing in face perception for autism spectrum disorder individuals. Taken together with previous findings, our results suggest that emotion judgment mainly depends on local processing, while identity judgment mainly depends on global processing., (© 2012 International Society for Autism Research, Wiley Periodicals, Inc.)