The Kiddie Schedule for Affective Disorders and Schizophrenia was modified for use in children and adolescents with autism by developing additional screening questions and coding options that reflect the presentation of psychiatric disorders in autism spectrum disorders. The modified instrument, the Autism Comorbidity Interview-Present and Lifetime Version (ACI-PL), was piloted and frequently diagnosed disorders, depression, ADHD, and OCD, were tested for reliability and validity. The ACI-PL provides reliable DSM diagnoses that are valid based on clinical psychiatric diagnosis and treatment history. The sample demonstrated a high prevalence of specific phobia, obsessive compulsive disorder, and ADHD. The rates of psychiatric disorder in autism are high and are associated with functional impairment.

The direct estimation of heritability from genome-wide common variant data as implemented in the program Genome-wide Complex Trait Analysis (GCTA) has provided a means to quantify heritability attributable to all interrogated variants. We have quantified the variance in liability to disease explained by all SNPs for two phenotypically-related neurobehavioral disorders, obsessive-compulsive disorder (OCD) and Tourette Syndrome (TS), using GCTA. Our analysis yielded a heritability point estimate of 0.58 (se = 0.09, p = 5.64e-12) for TS, and 0.37 (se = 0.07, p = 1.5e-07) for OCD. In addition, we conducted multiple genomic partitioning analyses to identify genomic elements that concentrate this heritability. We examined genomic architectures of TS and OCD by chromosome, MAF bin, and functional annotations. In addition, we assessed heritability for early onset and adult onset OCD. Among other notable results, we found that SNPs with a minor allele frequency of less than 5% accounted for 21% of the TS heritability and 0% of the OCD heritability. Additionally, we identified a significant contribution to TS and OCD heritability by variants significantly associated with gene expression in two regions of the brain (parietal cortex and cerebellum) for which we had available expression quantitative trait loci (eQTLs). Finally we analyzed the genetic correlation between TS and OCD, revealing a genetic correlation of 0.41 (se = 0.15, p = 0.002). These results are very close to previous heritability estimates for TS and OCD based on twin and family studies, suggesting that very little, if any, heritability is truly missing (i.e., unassayed) from TS and OCD GWAS studies of common variation. The results also indicate that there is some genetic overlap between these two phenotypically-related neuropsychiatric disorders, but suggest that the two disorders have distinct genetic architectures.

The purpose of this study was to investigate comorbid psychiatric disorders and psychotropic medication use among adults with autism spectrum disorder (ASD) ascertained as children during a 1980’s statewide Utah autism prevalence study (n = 129). Seventy-three individuals (56.6 %) met criteria for a current psychiatric disorder; 89 participants (69.0 %) met lifetime criteria for a psychiatric disorder. Caregivers reported a psychiatric diagnosis in 44 participants (34.1 %). Anxiety disorder had the highest current and lifetime prevalence (39.5 and 52.7 %, respectively). Participants with intellectual disability (n = 94, 72.8 %) were significantly less likely to have community-based diagnoses of anxiety (χ2 = 5.37, p = 0.02) or depression (χ2 = 13.18, p < 0.001) reported by caregivers. Seventy-six participants (58.9 %) were taking ≥1 psychotropic medication. Comorbid psychiatric disorders occur frequently in adults with ASD, though identifying these disorders poses a challenge in community settings. A greater understanding of the presentation of these conditions within this population will increase assessment validity and the potential for efficacious intervention.

Tourette Syndrome (TS) is a developmental disorder that has one of the highest familial recurrence rates among neuropsychiatric diseases with complex inheritance. However, the identification of definitive TS susceptibility genes remains elusive. Here, we report the first genome-wide association study (GWAS) of TS in 1285 cases and 4964 ancestry-matched controls of European ancestry, including two European-derived population isolates, Ashkenazi Jews from North America and Israel, and French Canadians from Quebec, Canada. In a primary meta-analysis of GWAS data from these European ancestry samples, no markers achieved a genome-wide threshold of significance (p<5 × 10−8); the top signal was found in rs7868992 on chromosome 9q32 within COL27A1 (p=1.85 × 10−6). A secondary analysis including an additional 211 cases and 285 controls from two closely-related Latin-American population isolates from the Central Valley of Costa Rica and Antioquia, Colombia also identified rs7868992 as the top signal (p=3.6 × 10−7 for the combined sample of 1496 cases and 5249 controls following imputation with 1000 Genomes data). This study lays the groundwork for the eventual identification of common TS susceptibility variants in larger cohorts and helps to provide a more complete understanding of the full genetic architecture of this disorder.

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