Autism Diagnostic Interview-Revised Research Articles

Shorter sleep duration is associated with social impairment and comorbidities in ASD.

Sleep disturbance, particularly insomnia, is common in children with autism spectrum disorders (ASD). Furthermore, disturbed sleep affects core symptoms and other related comorbidities. Understanding the causes and consequences of sleep disturbances in children with ASD is an important step toward mitigating these symptoms. To better understand the connection between sleep duration and ASD severity, we analyzed ASD-related symptoms using the Autism Diagnostic Interview-Revised (ADI-R), Autism Diagnostic Observation Schedule (ADOS), IQ scores, and parent reports of the average amount of time slept per night that were available in the medical histories of 2,714 children with ASD in the Simons Simplex Collection (SSC). The mean (SD) sleep duration was 555 minutes. Sleep duration and severity of core ASD symptoms were negatively correlated, and sleep duration and IQ scores were positively correlated. Regression results indicated that more severe social impairment, primarily a failure to develop peer relationships, is the core symptom most strongly associated with short sleep duration. Furthermore, increased severity for numerous maladaptive behaviors assessed on the Child Behavior Checklist, as well as reports of attention deficit disorder, depressive disorder, and obsessive compulsive disorder were associated with short sleep duration. Severity scores for social/communication impairment and restricted and repetitive behaviors (RRB) were increased, and IQ scores were decreased, for children reported to sleep ≤420 minutes per night (lower 5th percentile) compared to children sleeping ≥660 minutes (upper 95th percentile). Our results indicate that reduced amounts of sleep are related to more severe symptoms in children with ASD. Autism Res 2017. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. Autism Res 2017, 10: 1221-1238. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.

Characterizing regression in Phelan McDermid Syndrome (22q13 deletion syndrome)

PurposeTo describe the frequency and characteristics of developmental regression in a sample of 50 patients with Phelan McDermid Syndrome (PMS) and investigate the possibility of association between regression, epilepsy, and electroencephalogram (EEG) abnormalities and deletion size. MethodsThe Autism Diagnostic Interview-Revised (ADI-R) was used to evaluate regression in patients with a confirmed diagnosis of PMS. Information on seizure history and EEGs was obtained from medical record review. Deletion size was determined by DNA microarray. ResultsA history of regression at any age was present in 43% of all patients. Among those exhibiting regression, 67% had onset after the age of 30 months, affecting primarily motor and self-help skills. In 63% of all patients there was a history of seizures and a history of abnormal EEG was also present in 71%. No significant associations were found between regression and seizures or EEG abnormalities. Deletion size was significantly associated with EEG abnormalities, but not with regression or seizures. ConclusionThis study found a high rate of regression in PMS. In contrast to regression in autism, that often occurs earlier in development and affects language and social skills, we found regression in PMS most frequently has an onset in mid-childhood, affecting motor and self-help skills. We also found high rates of seizures and abnormal EEGs in patients with PMS. However, a history of abnormal EEG and seizures was not associated with an increased risk of regression. Larger deletion sizes were found to be significantly associated with a history of abnormal EEG.

Some children with autism have latent social skills that can be tested.

BackgroundThe idea of latent social skills in autism emerged as a possible interpretation of the rapid (but temporary) improvement of autistic subjects in oxytocin studies. We tested a hypothesis that a normal response to Item No 59 “Secure Base” from the third version of the Autism Diagnostic Interview – Revised (ADIR-59) could indicate the presence of latent social skills in autism.MethodsWe examined 110 autistic children (88 boys and 22 girls) with a mean age of 6.0±2.5 years (range: 2.2–14.8 years) using the Autism Diagnostic Observation Schedule (ADOS) – Generic. A diagnosis of mental retardation was established in 68 autistic children (62%).ResultsThe difference in the ADOS social domain between children aged ≤5 years on one side and children older than 5 years on the other side was significant in subjects with normal responses to ADIR-59 (9.60 vs 6.47; P=0.031) but not in those with abnormal responses to ADIR-59 (10.62 vs 9.63; P=0.537). In a predictive model, lower ADOS social domain scores were predicted by older age (P=0.001), lower scores on the ADIR-59 (P=0.01), and the absence of mental retardation (P=0.049).ConclusionThe results support the hypothesis that the normal response to item ADIR-59 “Secure Base” indicates the presence of latent social skills in autism that might foretell further social growth in older autistic subjects.

Sex Differences in Diagnosis and Clinical Phenotypes of Chinese Children with Autism Spectrum Disorder

The aim of this study was to explore the differences between boys and girls in the diagnosis and clinical phenotypes of autism spectrum disorder (ASD) in China's mainland. Children diagnosed with ASD (n = 1064, 228 females) were retrospectively included in the analysis. All children were assessed using the Autism Diagnostic Interview-Revised (ADI-R) and Autism Diagnostic Observation Schedule (ADOS). The results showed that girls scored significantly higher in ADI-R socio-emotional reciprocity than boys, and also scored lower in ADI-R and ADOS restricted and repetitive behaviors (RRBs). Meanwhile, the proportions of girls who satisfied the diagnostic cut-off scores in the ADI-R RRBs domain were lower than in boys (P < 0.05). Our results indicated that girls with ASD show greater socio-emotional reciprocity than boys. Girls also tended to show fewer RRBs than boys, and the type of RRBs in girls differ from those in boys. The ADI-R was found to be less sensitive in girls, particularly for assessment in the RRBs domain.

Brief Report: Examination of Correlates of Adaptive Behavior in Children with HFASD using the BASC-2 Parent Rating Scale.

This study extended the research on correlates of adaptive functioning of high-functioning children with autism spectrum disorder (HFASD) using the Behavior Assessment System for Children-Second Edition (BASC-2). Specifically, this study investigated the relationships between adaptive behavior and age, IQ, and ASD symptomology, in a well-characterized sample of 119 children with HFASD, ages 6-11years. Results revealed age and IQ were not significantly correlated with adaptive ability. However, total autism symptoms [measured by the Autism Diagnostic Interview-Revised(ADI-R)], as well as ASD-social symptoms were negatively correlated with adaptive ability. Mean comparisons revealed that participants falling into the clinically-significant range of the BASC-2 Adaptive Skills Composite (ASC)displayed significantly greater levels of both overall and social ASD symptoms.

Diagnostic Utility of the ADI-R and DSM-5 in the Assessment of Latino Children and Adolescents.

Latino children in the US are systematically underdiagnosed with Autism Spectrum Disorder (ASD); therefore, it is important that recent changes to the diagnostic process do not exacerbate this pattern of under-identification. Previous research has found that the Autism Diagnostic Interview-Revised (ADI-R) algorithm, based on the Diagnostic and Statistical Manual of Mental Disorder, Fourth Edition, Text Revision (DSM-IV-TR), has limitations with Latino children of Spanish speaking parents. We evaluated whether an ADI-R algorithm based on the new DSM-5 classification for ASD would be more sensitive in identifying Latino children of Spanish speaking parents who have a clinical diagnosis of ASD. Findings suggest that the DSM-5 algorithm shows better sensitivity than the DSM-IV-TR algorithm for Latino children.

Autism Spectrum and psychosis risk in the 22q11.2 deletion syndrome. Findings from a prospective longitudinal study

BackgroundIndividuals with 22q11.2 deletion syndrome (22q11DS) have a 25% risk for schizophrenia and related psychotic disorders. Some have hypothesized that Autism Spectrum Disorders (ASDs) diagnosed in children with 22q11DS may actually represent the social-communicative defects often observed during the early developmental stages of schizophrenia. MethodsWe prospectively studied 89 children with 22q11DS to test this hypothesis. At baseline, the Autism Diagnostic Interview was used to assess ASD, evaluating both current and early childhood behaviors. At follow-up, the Schedule for Affective Disorders and Schizophrenia for School-Age Children (K-SADS) was used to determine development of a psychotic disorder or psychotic symptoms. ResultsThe average age (±SD) at first and last assessments was 14.3±1.9 and 19.0±3.0years, respectively. Nineteen (21.3%) children developed a psychotic disorder. Contrary to our hypothesis, there was no significant difference in the proportion that developed a psychotic disorder, comparing those with (n=9, 17.3%) and those without ASD at baseline (n=10, 27%; OR=0.500, 95% CI=0.160–1.569, p=0.235). Similar results were obtained using autistic symptom severity as quantitative predicting variable, psychotic symptoms as the outcome, and when correcting for age, gender and full scale IQ. ConclusionResults indicate that in children with 22q11DS, early childhood autistic features are not associated with an increased risk for subsequent development of psychotic disorders or symptoms, replicating previous retrospective findings in adults with 22q11DS. These results indicate that ASD and psychotic disorders can emerge independently, as pleiotropic phenotypes in the context of 22q11DS.

Investigating the relationship between multiple grip forces and BOLD signal in the Cerebellum and dentate nuclei of MS subjects

Investigating the relationship between multiple grip forces and BOLD signal in the Cerebellum and dentate nuclei of MS subjects

T8. GLUTAMATERGIC SIGNALLING AND AUTISM: A FAMILY BASED ASSOCIATION STUDY ON THE GLUTAMATERGIC NEUROTRANSMITTER SYSTEM

Background Common single nucleotide polymorphisms (SNPs) explain around 50% of genetic risk underlying Autism-Spectrum-Disorder (ASD). In a previous study we showed that common functional SNPs of genes implicated in Fragile X Syndrome (FXS) were associated with ASD (Waltes et al., 2014). The FXS associated protein FMRP is regulated by the glutamatergic system, a patho-mechanism discussed for ASD. Objective We tested if functional common SNPs of glutamatergic genes were associated with ASD or ASD specific symptoms in two large ASD family cohorts (Autism Genome Project/AGP set, N=2734 families; German data set N=578 families). Since the genetic architecture between individuals with High IQ (HIQ= IQ>70) and Low IQ (LIQ= IQ≤70) differs (Vieland et al., 2010), we also split the two cohorts into high and low functioning (HIQ, LIQ) individuals. Methods 207 functional SNPs of 124 glutamatergic genes with a minor allele frequency over 5% were tested using Plink v 1.9 (DFAM) in the cohort with HIQ, LIQ and the combined cohorts, respectively. Phenotype association was studied by logistic ordinal regression correcting for gender, IQ, clinical site and population stratification. Phenotype measures were taken from the Autism Diagnostic Interview-Revised (ADI-R) scores for Social Interaction (Domain A), Verbal Communication (B1-B4; verbal individuals only), Non-Verbal Communication (Domain B2; B3; all individuals) and Repetitive Behavior (Domain C). Variants significant in both cohorts with effect sizes in the same direction were considered as replicated. Similarly, genes with any nominal significant variant in both cohorts were considered as replicated hits. Results We identified nominal significant associations of variants rs7206796 and rs3790112 (GNAO1) as well as rs3742926 (AKAP6) in both the German and the AGP LIQ cohort. In addition, significant but not overlapping SNPs of AKAP2 were identified (LIQ only). rs731826 (AKT1S1) was associated with Non Verbal Communication in the HIQ cohorts. In addition, we report 24 variants that were nominally associated with ADI-R scores in both cohorts. Genes that were involved in all five phenotypes tested were strongly related to the mTOR Pathway (e.g. genes MTOR and TSC2) or the second messenger system (e.g. G-proteins GNAS, phospholipases PLCB, protein phosphatases PPP1CA). A subset of genes was specific to each phenotype or significant in one of the subgroups (HIQ and LIQ) only. For example AKAP13 or RPS6K are associated with Verbal Communication in Low Functioning Individuals. Discussion Replication and extending previous findings we found that variants of genes that are associated with glutamate signaling, and specifically the mTOR pathway are modulators of ASD symptoms. Genes such as TSC1 or RPS6K are known to mediate glutamatergic signaling through mTOR, whereas AKAP proteins are important interactors of glutamate receptors (Sanderson et al., 2011). Both, the mTOR pathways and AKAP proteins have previously been associated with ASD (Chen et al ., 2014; Poelmans et al., 2013). Further functional analyses of glutamatergic variants are thus recommended to elucidate ASD etiology.

Narrative production in children with autism spectrum disorder (ASD) and children with attention-deficit/hyperactivity disorder (ADHD): Similarities and differences.

The present study focuses on the similarities and differences in language production between children with autism spectrum disorder (ASD) and children with attention-deficit/hyperactivity disorder (ADHD). In addition, we investigated whether Theory of Mind (ToM), working memory, and response inhibition are associated with language production. Narratives, produced by 106 Dutch-speaking children (36 with ASD, 34 with ADHD, and 36 typically developing) aged 6 to 12 during ADOS assessment, were examined on several linguistic measures: verbal productivity, speech fluency, syntactic complexity, lexical semantics, and discourse pragmatics. Children were tested on ToM, working memory, and response inhibition and parents filled in the Children's Communication Checklist (CCC-2). Gold-standard diagnostic measures (Autism Diagnostic Observation Schema [ADOS], Autism Diagnostic Interview Revised [ADI-R], and the Parent Interview for Child Symptoms [PICS]) were administered to all children to confirm diagnosis. Regarding similarities, both clinical groups showed impairments in narrative performance relative to typically developing children. These were confirmed by the CCC-2. These impairments were not only present on pragmatic measures, such as the inability to produce a narrative in a coherent and cohesive way, but also on syntactic complexity and their production of repetitions. As for differences, children with ADHD but not children with ASD showed problems in their choice of referring expressions and speech fluency. ToM and working memory performance but not response inhibition were associated with many narrative skills, suggesting that these cognitive mechanisms explain some of the impairments in language production. We conclude that children with ASD and children with ADHD manifest multiple and diverse language production problems, which may partly relate to their problems in ToM and working memory. (PsycINFO Database Record

M14 - SPECIFIC ASD PHENOTYPES ARE MODULATED BY DISTINCT GENETIC VARIANTS CONVERGING AT NETWORK LEVEL

Background Autism spectrum disorders (ASD) are a group of genetically and phenotypically heterogeneous neurodevelopmental disorders. Common genetic variants are currently estimated to account for over 50% of ASD liability, and are also suggested to contribute to phenotypic variability. Only few studies have reported association of genetic variants with quantitative ASD phenotypes and it is unclear if different phenotypic aspects of the disorder have a distinct etiology. Here, we aim at discovering associations of common variants with ASD related phenotypes. To interpret the findings in their biological context we mapped significant variants to their genes and tested for enriched pathways and networks implicated in brain development. Methods We investigated phenotype and genotype data of 637 German trios with ASD and of the Autism Genome Project cohort (2004 families). Both cohorts were harmonized and quality checked at phenotypic (Autism Diagnostic Interview Revised, ADI-R items) and genotypic (Illumina Microarrays) level. We performed factor analysis of 28 single items of the ADI-R used in the diagnostic algorithm. To increase genetic resolution and the number of overlapping variants between the two datasets we imputed common variants with a MAF>0.05 using the “1000 Genomes” data as reference. SNPs significantly associated with the phenotype were identified using regression models corrected for ancestry, gender and IQ. Significant variants identified in both, the German and the AGP cohort, were subjected to GO-term, KEGG, and pathway enrichment analysis. Gene-regulatory modules implicated in brain development were defined by weighted gene co-expression analysis using publicly available transcriptome data of the developing human brain (brainspan.org) and tested for enrichment with the associated gene sets. Results We extracted 5 factors of the ADI-R items labeled as joint attention, social interaction and communication, non-verbal communication, repetitive sensory-motor behavior and compulsion and restricted interests. Of the 7.5M variants with a MAF > 0.05 available after imputation and quality check over 500 were associated nominally significant and replicated with each factor respectively. Analysis of the underlying genes showed that the associated GO-terms were specific for each factor and reflected directly linked biological processes such “sensory processing” for repetitive sensory-motor behavior. Finally, we present developmental time-frames specifically enriched for associated gene-sets. Discussion Our findings suggest that each ASD related phenotype is underlying a specific genetic etiology. The identification of critical periods during development further allows understanding the effects of genetic variants at specific brain-developmental and brain-regional networks. These findings thus provided a deeper insight into the complex genetic architecture of ASD and increased our understanding of mechanisms modulating ASD phenotypes

Tumor necrosis factor-alpha expression in peripheral blood mononuclear cells correlates with early childhood social interaction in autism spectrum disorder

Autism spectrum disorder is a neurodevelopmental disorder characterized by impaired social interaction, poor communication skills, and repetitive/restrictive behaviors. Elevated blood levels of pro-inflammatory cytokines have been reported in subjects with autism spectrum disorder. On the other hand, early childhood adverse experience also increases blood levels of these cytokines. Since social experience of children with autism spectrum disorder is generally unlike to typically developing children, we hypothesized that social interaction during childhood contribute to pro-inflammatory cytokine expression in subjects with autism spectrum disorder. We compared revised Autism Diagnostic Interview scores and expression levels of pro-inflammatory cytokines in peripheral blood mononuclear cells of subjects with autism spectrum disorder (n = 30). The score of domain A on the revised Autism Diagnostic Interview, indicating social interaction impairment in early childhood, was negatively correlated with tumor necrosis factor-α mRNA expression level in peripheral blood mononuclear cells but not interleukin-1β or -6. Consistently, tumor necrosis factor-α mRNA expression was markedly low in subjects with autism spectrum disorder compared to typically developing children who presumably experienced the regular levels of social interaction. These findings suggest that the low blood levels of tumor necrosis factor-α mRNA in subjects with autism spectrum disorder might be due to impaired social interaction in early childhood.

Disparity in report of autism-related behaviors by social demographic characteristics: Findings from a community-based study in Taiwan.

The Social Communication Questionnaire is one of the most commonly used screening tools for autism spectrum disorder. The Social Communication Questionnaire is a caregiver-reported questionnaire with 40 items based on questions from the Autism Diagnostic Interview-Revised. This study collected Social Communication Questionnaire data from a community-based, multi-stage case identification design epidemiologic study in one socioeconomically disadvantaged county in Taiwan. The Social Communication Questionnaire was distributed to 3034 school children, aged 6-8 years. Item prevalence results indicate males were reported to have more autism-related behaviors than females (higher prevalence on most items), in the whole study sample as well as in children meeting Social Communication Questionnaire clinical cut-offs (⩾15). Children whose biological fathers completed the Social Communication Questionnaire were reported to have more behavioral issues than children whose biological mothers were the respondent. Lower respondent education levels were associated with reports of clinically concerning autism-related behaviors. However, males were not at higher risk of meeting Social Communication Questionnaire clinical cut-offs than females in this study population. Findings from this study help to better understand reporting patterns on children's autism-related behaviors potentially due to social demographic characteristics and child sex, which may lead to improved identification of these behaviors.

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.

1.6 A SYSTEMATIC REVIEW OF SCREENING FOR AUTISM SPECTRUM DISORDER

No studies have systematically examined the validity of ASD-screening tools compared with the gold standard diagnostic procedures—the Autism Diagnostic Observation Schedule (ADOS) and the Autism Diagnostic Interview, Revised (ADI-R). Furthermore, extant reviews mostly focused on young children despite an increased need for reliable and valid tools that clinicians can use to assess school-age children, adolescents, and young adults. To address limitations of existing reviews of the validity of ASD-screening tools and clinical gaps, we conducted a review of ASD-screening tools.

Multidimensional Influences on Autism Symptom Measures: Implications for Use in Etiological Research

Growing awareness that symptoms of autism spectrum disorder (ASD) transcend multiple diagnostic categories, and major advances in the identification of genetic syndromes associated with ASD, have led to widespread use of ASD symptom measures in etiologic studies of neurodevelopmental disorders. Insufficient consideration of potentially confounding factors such as cognitive ability or behavior problems can have important negative consequences in interpretation of findings, including erroneous estimation of associations between ASD and etiologic factors. Participants were 388 children 2 to 13 years old with diagnoses of ASD or another neurodevelopmental disorder without ASD. Receiver operating characteristics methods were used to assess the influence of IQ and emotional and behavioral problems on the discriminative ability of 3 widely used ASD symptom measures: the Social Responsiveness Scale (SRS), the Autism Diagnostic Interview-Revised (ADI-R), and the Autism Diagnostic Observation Schedule (ADOS). IQ influenced the discriminative thresholds of the SRS and ADI-R, and emotional and behavioral problems affected the discriminative thresholds of the SRS, ADI-R, and ADOS. This resulted in low specificity of ASD cutoffs on the SRS and ADI-R for children with intellectual disability without ASD (27-42%) and low specificity across all 3 instruments for children without ASD with increased emotional and behavioral problems (36-59%). Adjustment for these characteristics resulted in improved discriminative ability for all of the ASD measures. The findings indicate that scores on ASD symptom measures reflect far more than ASD symptoms. Valid interpretation of scores on these measures requires steps to account for the influences of IQ and emotional and behavioral problems.

Sensorimotor Difficulties Are Associated with the Severity of Autism Spectrum Conditions.

Present diagnostic criteria for autism spectrum conditions (ASC) include social communication and interaction difficulties, repetitive behavior and movement, and atypical sensory responsivity. Few studies have explored the influence of motor coordination and sensory responsivity on severity of ASC symptoms. In the current study, we explore whether sensory responsivity and motor coordination differences can account for the severity of autistic behaviors in children with ASC. Thirty-six children participated: 18 (13 male, 5 female) with ASC (ages 7–16: mean age = 9.93 years) and 18 (7 male, 11 female) typically developing (TD) children (ages 6–12; mean age = 9.16 years). Both groups completed a battery of assessments that included motor coordination, sensory responsivity, receptive language, non-verbal reasoning and social communication measures. Children with ASC also completed the Autism Diagnostic Observation Schedule (ADOS) and Autism Diagnostic Interview—Revised (ADI-R). Results showed that children with ASC scored significantly lower on receptive language, coordination, sensory responsivity and a sensorimotor subscale, Modulation of Activity (MoA) compared to the TD group. In the ASC group, MoA significantly predicted ASC severity across all ASC measures; receptive language and sensory responsivity significantly predicted parental reported autism measures; and coordination significantly predicted examiner observed reported scores. Additionally, specific associations were found between the somatosensory perceptive modalities and ASC severity. The results show that sensorimotor skills are associated with severity of ASC symptoms; furthering the need to research sensorimotor integration in ASC and also implying that diagnosis of ASC should also include the assessment of both coordination deficit and atypical sensory responsivity.

Equivalence of symptom dimensions in females and males with autism

This study investigated equivalence of autism symptom domains in males and females with autism. Symptom data were obtained from 2643 children and adolescents with autism spectrum disorder (352 females, 2291 males; age range = 4-17 years) included in the Simons Simplex Collection. Items from the Social Responsiveness Scale and Autism Diagnostic Interview-Revised were mapped to nine a priori symptom dimensions. Multi-group confirmatory factor models, including measurement equivalence and item response theory analyses, examined whether males and females showed measurement or structural differences in autism symptom constructs. Results indicated mean differences in restricted interests that were not due to measurement bias. No other symptom dimension showed evidence of measurement bias and autism symptom structure was highly similar between males and females. Future studies are needed to carefully estimate any sex differences in the content, frequency, or intensity/severity of restricted interests in females and males.

Sex bias in autism spectrum disorder in neurofibromatosis type 1

BackgroundDespite extensive literature, little is known about the mechanisms underlying sex bias in autism spectrum disorder (ASD). This study investigates the sex differences in ASD associated with neurofibromatosis type 1, a single-gene model of syndromic autism.MethodsWe analysed data from n = 194 children aged 4–16 years with neurofibromatosis type 1. Sex differences were evaluated across the Autism Diagnostic Interview-Revised (ADI-R), Autism Diagnostic Observation Schedule (ADOS), verbal IQ, Social Responsiveness Scale (SRS) and Conners questionnaires.ResultsThere was 2.68:1 male:female ratio in children meeting ASD criteria on the deep phenotyping measures. On symptom profile, males with neurofibromatosis type 1 (NF1) + ASD were more impaired on reciprocal social interaction and communication domains of the ADI-R but we found no differences on the restricted, repetitive behaviours (RRBs) domain of the ADI-R and no differences on the social on the ADOS. NF1 ASD males and females were comparable on verbal IQ, and the inattention/hyperactivity domains of the Conners questionnaire.ConclusionsThere is a significant male bias in the prevalence of ASD in NF1. The phenotypic profile of NF1 + ASD cases includes greater social communication impairment in males. We discuss the implications of our findings and the rationale for using NF1 as a model for investigating sex bias in idiopathic ASD.

Non-ASD outcomes at 36 months in siblings at familial risk for autism spectrum disorder (ASD): A baby siblings research consortium (BSRC) study.

We characterized developmental outcomes of a large sample of siblings at familial high-risk of autism spectrum disorder (ASD), who themselves did not have ASD (n = 859), and low-risk controls with no family history of ASD (n = 473). We report outcomes at age 3 years using the Mullen Scales of Early Learning, the Autism Diagnostic Observation Schedule (ADOS), the Autism Diagnostic Interview-Revised (ADI-R) and adaptive functioning on the Vineland Adaptive Behavior Scales. Around 11% of high-risk siblings had mild-to-moderate levels of developmental delay, a rate higher than the low-risk controls. The groups did not differ in the proportion of toddlers with mild-to-moderate language delay. Thirty percent of high-risk siblings had elevated scores on the ADOS, double the rate seen in the low-risk controls. High-risk siblings also had higher parent reported levels of ASD symptoms on the ADI-R and lower adaptive functioning on the Vineland. Males were more likely to show higher levels of ASD symptoms and lower levels of developmental ability and adaptive behavior than females across most measures but not mild-to-moderate language delay. Lower maternal education was associated with lower developmental and adaptive behavior outcomes. These findings are evidence for early emerging characteristics related to the "broader autism phenotype" (BAP) previously described in older family members of individuals with ASD. There is a need for ongoing clinical monitoring of high-risk siblings who do not have an ASD by age 3 years, as well as continued follow-up into school age to determine their developmental and behavioral outcomes. Autism Res 2017, 10: 169-178. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.