Genome-wide association study of response to cognitive behavioural therapy in children with anxiety disorders

Background Anxiety disorders are common, and cognitive–behavioural therapy (CBT) is a first-line treatment. Candidate gene studies have suggested a genetic basis to treatment response, but findings have been inconsistent. Aims To perform the first genome-wide association study (GWAS) of psychological treatment response in children with anxiety disorders (n = 980). Method Presence and severity of anxiety was assessed using semi-structured interview at baseline, on completion of treatment (post-treatment), and 3 to 12 months after treatment completion (follow-up). DNA was genotyped using the Illumina Human Core Exome-12v1.0 array. Linear mixed models were used to test associations between genetic variants and response (change in symptom severity) immediately post-treatment and at 6-month follow-up. Results No variants passed a genome-wide significance threshold (P = 5×10−8) in either analysis. Four variants met criteria for suggestive significance (P<5×10−6) in association with response post-treatment, and three variants in the 6-month follow-up analysis. Conclusions This is the first genome-wide therapygenetic study. It suggests no common variants of very high effect underlie response to CBT. Future investigations should maximise power to detect single-variant and polygenic effects by using larger, more homogeneous cohorts.

The interface of syntax with pragmatics and prosody in children with Autism Spectrum Disorders

In order to study problems of individuals with Autism Spectrum Disorders (ASD) with morphosyntax, we investigated twenty high-functioning Greek-speaking children (mean age:6;11) and twenty age- and language-matched typically developing children on environments that allow or forbid object clitics or their corresponding noun phrase. Children with ASD fell behind typically developing in comprehending and producing simple clitics and producing noun phrases in focus structures. The two groups performed similarly in comprehending and producing clitics in clitic left dislocation and in producing noun phrases in non-focus structures. We argue that children with ASD have difficulties at the interface of(morpho)syntax with pragmatics and prosody, namely, distinguishing a discourse prominent element, and considering intonation relevant for a particular interpretation that excludes clitics.