Genome-Wide Association Study of Symptom Change Following Cognitive Behavioral Therapy for Common Mental Disorders

Cognitive behavioral therapy (CBT) is a well-established, evidence-based treatment for common mental disorders such as depression, anxiety disorders, and obsessive-compulsive disorder (OCD). However, treatment outcomes vary widely, and a substantial proportion of patients do not achieve sufficient improvement. Robust predictors of individual differences in symptom change are currently lacking. Genetic differences have been suggested to play a role, but existing evidence is inconclusive. This study investigated the extent to which common genetic variants-single nucleotide polymorphisms (SNPs)-contribute to variability in symptom change. The sample was derived from the MULTI-PSYCH and NORDiC cohorts, comprising 3113 adults and children treated with CBT for depression, panic disorder, social anxiety disorder, or OCD. We performed a genome-wide association study (GWAS) of symptom change following CBT and estimated the proportion of variance attributed to SNPs. Secondary analyses included GWAS and SNP-based heritability estimation of additional clinically relevant outcomes: pre- and post-treatment symptom severity and remission status. No variants reached genome-wide significance. We estimated SNP-based heritability of symptom change at $h_{\mathrm{SNP}}^2$  = 0.221 (SE = 0.123). These results suggest that common genetic variation may contribute modestly to treatment outcomes. Much larger samples would be required to obtain more precise estimates and to detect genome-wide significant loci.