Interrogating Associations between Polygenic Liabilities and Electroconvulsive Therapy Effectiveness

Abstract Background Electroconvulsive therapy (ECT) is the most effective treatment for severe major depressive episodes (MDE). Nonetheless, firmly established associations between ECT outcomes and biological variables are currently lacking. Polygenic risk scores (PRSs) carry clinical potential but associations with treatment response in psychiatry are seldom reported. Here, we examined whether PRSs for major depressive disorder, schizophrenia, cross-disorder, and pharmacological antidepressant response are associated with ECT effectiveness. Methods 288 patients with MDE from three countries were included. The main outcome was 17-item Hamilton Depression Rating Scale change (ΔHDRS) scores from before to after ECT treatment. Secondary outcomes were response and remission. Regression analyses with PRSs as independent variables and several covariates were performed. Explained variance (R2) at the optimal p-value threshold (oPt) is reported. Results In the 266 subjects passing quality control, PRS-schizophrenia was positively associated with larger HDRS decrease in linear regression (oPt=0.05, R2=6.94%, p Conclusions A linear association between PRS-SCZ and ECT outcome was uncovered. Although it is too early to adopt PRSs in ECT clinical decision-making, these findings strengthen the positioning of PRS-SCZ as relevant to treatment response in psychiatry.