SummaryAlthough autism is a highly heritable neurodevelopmental disorder, attempts to identify specific susceptibility genes have thus far met with limited success 1. Genome-wide association studies (GWAS) using half a million or more markers, particularly those with very large sample sizes achieved through meta-analysis, have shown great success in mapping genes for other complex genetic traits (http://www.genome.gov/26525384). Consequently, we initiated a linkage and association mapping study using half a million genome-wide SNPs in a common set of 1,031 multiplex autism families (1,553 affected offspring). We identified regions of suggestive and significant linkage on chromosomes 6q27 and 20p13, respectively. Initial analysis did not yield genome-wide significant associations; however, genotyping of top hits in additional families revealed a SNP on chromosome 5p15 (between SEMA5A and TAS2R1) that was significantly associated with autism (P = 2 × 10−7). We also demonstrated that expression of SEMA5A is reduced in brains from autistic patients, further implicating SEMA5A as an autism susceptibility gene. The linkage regions reported here provide targets for rare variation screening while the discovery of a single novel association demonstrates the action of common variants.

We examined social anxiety and internalizing symptoms using the Social Phobia and Anxiety Inventory for Children (SPAI-C), the Social Anxiety Scale for Children -Revised (SASC-R), and the Child Behavior Checklist (CBCL) in a sample of fifty-four high-functioning subjects with autism or Asperger syndrome (HFA/AS) (M = 11.2 +/- 1.7 years) and 305 community subjects (M = 12.2 +/- 2.2 years). Children and adolescents completed the SPAI-C and SASC-R, and their parents completed the CBCL Internalizing scale. Adolescents with HFA/AS scored higher than the community sample on all measures. Behavioural avoidance and evaluative social anxiety increased by age within the HFA/AS group, whereas behavioural avoidance decreased by age in control participants. Data support that HFA/AS in adolescents may be associated with clinically relevant social anxiety symptoms.

The present study identifies the prevalence and types of comorbid psychiatric disorders associated with Asperger syndrome (AS)/high-functioning autism (HFA) in a combined community- and clinic-based sample of fifty 9- to 16-year-old subjects using the Schedule for Affective Disorders and Schizophrenia for School-Age Children, Present and Lifetime Version. The level of functioning was estimated using the Children's Global Assessment Scale. The results support common (prevalence 74%) and often multiple comorbid psychiatric disorders in AS/HFA; behavioral disorders were shown in 44%, anxiety disorders in 42% and tic disorders in 26%. Oppositional defiant disorder, major depressive disorder and anxiety disorders as comorbid conditions indicated significantly lower levels of functioning. To target interventions, routine evaluation of psychiatric comorbidity in subjects with AS/HFA is emphasized.

Objectives: We examine whether pregnancy weight (pre-pregnancy body mass index (BMI) and/or weight gain) is related to core symptoms of attention deficit hyperactivity disorder (ADHD) in school-age offspring. Design: Follow-up of prospective pregnancy cohorts from Sweden, Denmark and Finland within the Nordic Network on ADHD. Methods: Maternal pregnancy and delivery data were collected prospectively. Teachers rated inattention and hyperactivity symptoms in offspring. High scores were defined as at least one core symptom rated as 'severe' and two as 'present' (approximately 10% of children scored in this range). Logistic regression and latent class analyses were used to examine maternal pregnancy weight in relation to children's ADHD core symptoms. Results: Teacher rated 12 556 school-aged children. Gestational weight gain outside of the Institute of Medicine guidelines was not related to ADHD symptoms (below recommendations: odds ratio (OR): 0.96; 95% confidence interval (CI): 0.81, 1.14; above recommendations: OR: 0.98; 95% CI: 0.82, 1.16). To examine various patterns of pre-pregnancy BMI and weight gain, we used latent class analysis and found significant associations between classes that included pre-pregnancy overweight or obesity and a high ADHD symptom score in offspring, ORs ranged between 1.37 (95% CI: 1.07, 1.75) and 1.89 (95% CI: 1.13, 3.15) adjusted for gestational age, birth weight, weight gain, pregnancy smoking, maternal age, maternal education, child gender, family structure and cohort country of origin. Children of women who were both overweight and gained a large amount of weight during gestation had a 2-fold risk of ADHD symptoms (OR: 2.10, 95% CI: 1.19, 3.72) compared to normal-weight women. Conclusions: We show for the first time that pre-pregnancy BMI is associated with ADHD symptoms in children. Our results are of public health significance if the associations are causal and will then add ADHD symptoms in offspring to the list of deleterious outcomes related to overweight and obesity in the prenatal period.