Efficacy of Community-Delivered PEERS® for Adolescents: Increases in Social Skills and Decreases in Social Anxiety and Loneliness.

PURPOSE: PEERS® for Adolescents is an evidence-based social skills training program developed for individuals with autism spectrum disorder (ASD), which is now widely implemented by community providers in clinics and schools. However, majority of past efficacy studies on PEERS® were conducted in controlled research settings, with limited information about its effectiveness when delivered in the community. We sought to examine the effects of PEERS® on social functioning and mental health outcomes when delivered in an outpatient autism specialty clinic. METHODS: Clinical data from 45 adolescents with social challenges (age range: 11-18 years old; 31.1% female assigned at birth) were extracted for secondary analyses. Paired t-tests were performed to examine the pre- to post-intervention changes in social and mental health outcomes. Correlations between pre- and post-change scores of outcome measures were examined. RESULTS: Self-reported social skills knowledge, caregiver-reported social skills (measured by the Social Skills Improvement Systems) and the number of get-togethers hosted, increased significantly from pre- to post-intervention. Additionally, caregiver-reported anxiety and self-reported loneliness significantly decreased from pre- to post-intervention. Exploratory analyses showed that increases in caregiver-reported social skills were associated with decreases in self-reported loneliness. CONCLUSIONS: Our findings provide evidence supporting the efficacy of PEERS® for improving social knowledge and skills of adolescents with social challenges when delivered in the community. The current study also showed the potential benefit of PEERS® for improving adolescent mental health.

Improving Social Knowledge and Skills among Adolescents with Autism: Systematic Review and Meta-Analysis of UCLA PEERS® for Adolescents.

UCLA PEERS® for Adolescents is a widely applied program among a number of social skills training programs developed over the years. We synthesized current research evidence on the PEERS program to evaluate the treatment effect on four commonly used outcome measures. 12 studies met inclusion criteria for the review and nine met the criteria for meta-analysis. Results showed moderate to large pooled effects across measures and informants in favor of the PEERS program, with the largest effect seen in social knowledge improvement and the smallest effect in the frequency of get-togethers. The heterogeneity of effects across studies were examined and the limitations of the current evidence were discussed.

Whole exome sequencing in extended families with autism spectrum disorder implicates four candidate genes.

Autism spectrum disorders (ASDs) are a group of neurodevelopmental disorders, characterized by impairment in communication and social interactions, and by repetitive behaviors. ASDs are highly heritable, and estimates of the number of risk loci range from hundreds to >1000. We considered 7 extended families (size 12-47 individuals), each with ≥3 individuals affected by ASD. All individuals were genotyped with dense SNP panels. A small subset of each family was typed with whole exome sequence (WES). We used a 3-step approach for variant identification. First, we used family-specific parametric linkage analysis of the SNP data to identify regions of interest. Second, we filtered variants in these regions based on frequency and function, obtaining exactly 200 candidates. Third, we compared two approaches to narrowing this list further. We used information from the SNP data to impute exome variant dosages into those without WES. We regressed affected status on variant allele dosage, using pedigree-based kinship matrices to account for relationships. The p value for the test of the null hypothesis that variant allele dosage is unrelated to phenotype was used to indicate strength of evidence supporting the variant. A cutoff of p = 0.05 gave 28 variants. As an alternative third filter, we required Mendelian inheritance in those with WES, resulting in 70 variants. The imputation- and association-based approach was effective. We identified four strong candidate genes for ASD (SEZ6L, HISPPD1, FEZF1, SAMD11), all of which have been previously implicated in other studies, or have a strong biological argument for their relevance.

Epigenetics of autism-related impairment: copy number variation and maternal infection.

OBJECTIVE: Epidemiological data have suggested maternal infection and fever to be associated with increased risk of autism spectrum disorder (ASD). Animal studies show that gestational infections perturb fetal brain development and result in offspring with the core features of autism and have demonstrated that behavioral effects of maternal immune activation are dependent on genetic susceptibility. The goal of this study was to explore the impact of ASD-associated copy number variants (CNVs) and prenatal maternal infection on clinical severity of ASD within a dataset of prenatal history and complete genetic and phenotypic findings. METHODS: We analyzed data from the Simons Simplex Collection sample including 1971 children with a diagnosis of ASD aged 4 to 18 years who underwent array comparative genomic hybridization screening. Information on infection and febrile episodes during pregnancy was collected through parent interview. ASD severity was clinically measured through parent-reported interview and questionnaires. RESULTS: We found significant interactive effects between the presence of CNVs and maternal infection during pregnancy on autistic symptomatology, such that individuals with CNVs and history of maternal infection demonstrated increased rates of social communicative impairments and repetitive/restricted behaviors. In contrast, no significant interactions were found between presence of CNVs and prenatal infections on cognitive and adaptive functioning of individuals with ASD. CONCLUSIONS: Our findings support a gene-environment interaction model of autism impairment, in that individuals with ASD-associated CNVs are more susceptible to the effects of maternal infection and febrile episodes in pregnancy on behavioral outcomes and suggest that these effects are specific to ASD rather than to global neurodevelopment.

Nonverbal and verbal cognitive discrepancy profiles in autism spectrum disorders: influence of age and gender.

Research suggests that discrepant cognitive abilities are more common in children with autism spectrum disorder (ASD) and may indicate an important ASD endophenotype. The current study examined the frequency of IQ discrepancy profiles (nonverbal IQ > verbal IQ [NVIQ > VIQ], verbal IQ > nonverbal IQ [VIQ > NVIQ], and no split) and the relationship of gender, age, and ASD symptomatology to IQ discrepancy profile in a large sample of children with ASD. The NVIQ > VIQ profile occurred at a higher frequency than expected, had more young males, and showed more autism symptoms than the other groups. Results suggest that the NVIQ > VIQ profile may be less likely to represent a subtype of ASD, but rather a common developmental pathway for children with ASD and other disorders.

Multiplex targeted sequencing identifies recurrently mutated genes in autism spectrum disorders.

Exome sequencing studies of autism spectrum disorders (ASDs) have identified many de novo mutations but few recurrently disrupted genes. We therefore developed a modified molecular inversion probe method enabling ultra-low-cost candidate gene resequencing in very large cohorts. To demonstrate the power of this approach, we captured and sequenced 44 candidate genes in 2446 ASD probands. We discovered 27 de novo events in 16 genes, 59% of which are predicted to truncate proteins or disrupt splicing. We estimate that recurrent disruptive mutations in six genes-CHD8, DYRK1A, GRIN2B, TBR1, PTEN, and TBL1XR1-may contribute to 1% of sporadic ASDs. Our data support associations between specific genes and reciprocal subphenotypes (CHD8-macrocephaly and DYRK1A-microcephaly) and replicate the importance of a ß-catenin-chromatin-remodeling network to ASD etiology.