Association Between Polygenic Risk and Symptom Severity Change After Cognitive Behavioral Therapy for Obsessive-Compulsive Disorder

Abstract

A large proportion of patients undergoing cognitive behavior therapy (CBT) for obsessive-compulsive disorder (OCD) do not respond sufficiently to treatment. Identifying predictors for change in symptom severity after treatment could inform clinical decision-making, allow for better-tailored interventions, and avoid treatment failure. Prior research on predictors for treatment response has, however, yielded inconsistent findings with limited clinical utility. Here, we investigated the predictive power of nine polygenic risk scores (PRSs) for psychiatric and cognitive traits in 1598 OCD patients (1167 adults and 431 children/adolescents) treated with CBT in Sweden and Norway. We fitted linear mixed models adjusted for age, sex, genotyping batch, and the first five ancestry PCs to estimate associations between PRS and symptom severity change from pre- to post-treatment. The PRS for schizophrenia showed a modestly significant association with symptom change (β = 0.013, p = 0.04, R ² = 0.10), indicating that a higher PRS for schizophrenia was associated with a smaller decrease in symptom severity. No other PRS were significantly associated with the outcome. While these results await replication and expansion, current PRS for psychiatric and cognitive phenotypes do not seem to contribute meaningfully to symptom severity change in CBT for OCD.