Do polygenic risk and stressful life events predict pharmacological treatment response in obsessive compulsive disorder? A gene\u2013environment interaction approach

María Alemany-Navarro,Javier Costas,Laura Domènech,Ángel Carracedo,Pino Alonso,Raquel Rabionet,Eva Real,Cinto Segalàs,Sara Bertolín,Jose M Menchón

doi:10.1038/s41398-019-0410-0

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.

Highlights

Background ObsessiveCompulsive Disorder (OCD) is a complex neuropsychiatric condition that may interfere severely in the patient’s life and lead to maladaptive behavior[1,2]
Comparison with previous genome-wide association study (GWAS) Our results were compared with the available data from previous GWAS studies: single nucleotide polymorphism (SNP) at P < 01 × 10−3 in metaanalysis of Stewart et al.53. and SNPs at P < 01 × 10−4 in the study of Matthiesen et al.[54]
This study was conducted to analyze if a polygenic risk score (PRS) composed of Obsessive-compulsive disorder (OCD)-risk genetic variants predicted treatment response in a sample of OCD patients, and whether this relation was modulated by stressful life events (SLEs) at onset

Summary

Introduction

Compulsive Disorder (OCD) is a complex neuropsychiatric condition that may interfere severely in the patient’s life and lead to maladaptive behavior[1,2]. Lifetime prevalence of the disorder is 2–3%3. Treatment usually consists of medication and cognitive-behavioral therapy, as recommended in OCD clinical guidelines[4]. Selective serotonin reuptake inhibitors (SSRIs) comprise the first-line pharmacological treatment for OCD. Treatment response is variable, with the proportion of OCD patients that improve with pharmacological treatment oscillating between 40 and 70%, and in some cases only a partial response is obtained[5]. Nonresponders may be treated with another SSRI6, with antipsychotics as adjunctive treatment[7], or clomipramine either as monotherapy or as a coadjuvant[8]

Objectives

Methods

Results

Conclusion