Association of the Polygenic Scores for Personality Traits and Response to Selective Serotonin Reuptake Inhibitors in Patients with Major Depressive Disorder.

Azmeraw T Amare,Olli Kampman,Joanna M Biernacka,Russ B Altman,Shinpei Nonen,Julia C Stingl,Ari Illi,Jürgen Brockmöller,Teri E Klein,William V Bobo,Klaus Oliver Schubert,Anthony Batzler,Taisei Mushiroda,Verayuth Praphanphoj,Volker Arolt,Masaki Kato,Michiaki Kubo,Yuan Ji,Bernhard T Baune,Katharina Domschke,Katrin Sangkuhl,Poulami Barman,Richard M Weinshilboum,Liewei Wang,Toshihiko Kinoshita,Shih Jen Tsai ,Yu Li Liu ,Yi Hsiang Hsu ,Daniel K Hall‐Flavin ,Chia Hui Chen ,Michelle Skime ,Esa Leìnonen ,Fasil Tekola‐Ayele ,Ryan Whaley ,Hong Chen ,Ying‐Jay Liou ,Gregory D Jenkins

doi:10.3389/fpsyt.2018.00065

Abstract

Studies reported a strong genetic correlation between the Big Five personality traits and major depressive disorder (MDD). Moreover, personality traits are thought to be associated with response to antidepressants treatment that might partly be mediated by genetic factors. In this study, we examined whether polygenic scores (PGSs) derived from the Big Five personality traits predict treatment response and remission in patients with MDD who were prescribed selective serotonin reuptake inhibitors (SSRIs). In addition, we performed meta-analyses of genome-wide association studies (GWASs) on these traits to identify genetic variants underpinning the cross-trait polygenic association. The PGS analysis was performed using data from two cohorts: the Pharmacogenomics Research Network Antidepressant Medication Pharmacogenomic Study (PGRN-AMPS, n = 529) and the International SSRI Pharmacogenomics Consortium (ISPC, n = 865). The cross-trait GWAS meta-analyses were conducted by combining GWAS summary statistics on SSRIs treatment outcome and on the personality traits. The results showed that the PGS for openness and neuroticism were associated with SSRIs treatment outcomes at p < 0.05 across PT thresholds in both cohorts. A significant association was also found between the PGS for conscientiousness and SSRIs treatment response in the PGRN-AMPS sample. In the cross-trait GWAS meta-analyses, we identified eight loci associated with (a) SSRIs response and conscientiousness near YEATS4 gene and (b) SSRI remission and neuroticism eight loci near PRAG1, MSRA, XKR6, ELAVL2, PLXNC1, PLEKHM1, and BRUNOL4 genes. An assessment of a polygenic load for personality traits may assist in conjunction with clinical data to predict whether MDD patients might respond favorably to SSRIs.

Highlights

A major depressive disorder (MDD) is the most common and disabling mental health diseases worldwide [1, 2] with a lifetime prevalence of ~12% [3]
We analyzed data from 1,394 MDD patients who had selective serotonin reuptake inhibitors (SSRIs) treatment divided into PGRN-AMPS (n = 529) and ISPC (n = 865) samples
Polygenic scores were computed for each of the Big Five personality traits, and we investigated their association with two SSRI treatment outcomes—response and remission, after 4 weeks (PGRN-AMPS and ISPC) and 8 weeks (PGRN-AMPS) of treatment

Summary

Introduction

A major depressive disorder (MDD) is the most common and disabling mental health diseases worldwide [1, 2] with a lifetime prevalence of ~12% [3]. Studies estimated a 61.6 million years of life lived with disability caused by MDD accounting for 2.5% of the total disability-adjusted life years and for 8.1% of the total years lived with disability resulted from all diseases [2, 4]. Selective serotonin reuptake inhibitors (SSRIs) are commonly used as the first-line pharmacological treatment for MDD [5]. Treatment efficacy with SSRIs varies widely between individual patients and is inadequate in many cases. Clinical response rates range from 48 to 64% [6, 7] and reported remission rates are as low as 23.5% [7, 8]. An investigation of the biological and psychosocial factors that drive heterogeneity in treatment outcomes is necessary

Methods

Results

Conclusion