Do polygenic risk and stressful life events predict pharmacological treatment response in obsessive compulsive disorder? A gene-environment interaction approach

Abstract

The rate of response to pharmacological treatment in Obsessive-compulsive disorder (OCD) oscillates between 40 and 70%. Genetic and environmental factors have been associated with treatment response in OCD. This study analyzes the predictive ability of a polygenic risk score (PRS) built from OCD-risk variants, for treatment response in OCD, and the modulation role of stressful life events (SLEs) at the onset of the disorder. PRSs were calculated for a sample of 103 patients. Yale-Brown Obsessive Compulsive Scale (YBOCS) scores were obtained before and after a 12-week treatment. Regression analyses were performed to analyze the influence of the PRS and SLEs at onset on treatment response. PRS did not predict treatment response. The best predictive model for post-treatment YBOCS (post YBOCS) included basal YBOCS and age. PRS appeared as a predictor for basal and post YBOCS. SLEs at onset were not a predictor for treatment response when included in the regression model. No evidence for PRS predictive ability for treatment response was found. The best predictor for treatment response was age, agreeing with previous literature specific for SRI treatment. Suggestions are made on the possible role of neuroplasticity as a mediator on this association. PRS significantly predicted OCD severity independent on pharmacological treatment. SLE at onset modulation role was not evidenced. Further research is needed to elucidate the genetic and environmental bases of treatment response in OCD. ; his study was supported in part by the Carlos III Health Institute (PI13/01958, PI13/00918, PI14/00413 and PI16/00950); FEDER funds ('A way to build Europe') and by the Agency of University and Research Funding Management of the Catalan Government (2014SGR1672). We also acknowledge support of the Spanish Ministry of Economy and Competitiveness, 'Centro de Excelencia Severo Ochoa 2017-2021', SEV-2016-0571 and of the Spanish MINECO SAF2013-49108-R Plan Estatal. M.A. was supported by the Secretariat for Universities and Research of the Ministry of Business and Knowledge of the Government of Catalonia. Grant co-funded by the European Social Fund (ESF) "ESF, Investing in your future" (2017 FI_B 00327). E.R. was supported by a Juan Rodés contract (JR14/00038).