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01-01-2019 | Obesity | Psychiatry and Preclinical Psychiatric Studies - Original Article

The association of obesity and coronary artery disease genes with response to SSRIs treatment in major depression

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

Published in: Journal of Neural Transmission | Issue 1/2019

Abstract

Selective serotonin reuptake inhibitors (SSRIs) are first-line antidepressants for the treatment of major depressive disorder (MDD). However, treatment response during an initial therapeutic trial is often poor and is difficult to predict. Heterogeneity of response to SSRIs in depressed patients is partly driven by co-occurring somatic disorders such as coronary artery disease (CAD) and obesity. CAD and obesity may also be associated with metabolic side effects of SSRIs. In this study, we assessed the association of CAD and obesity with treatment response to SSRIs in patients with MDD using a polygenic score (PGS) approach. Additionally, we performed cross-trait meta-analyses to pinpoint genetic variants underpinnings the relationship of CAD and obesity with SSRIs treatment response. First, PGSs were calculated at different p value thresholds (P_T) for obesity and CAD. Next, binary logistic regression was applied to evaluate the association of the PGSs to SSRIs treatment response in a discovery sample (ISPC, N = 865), and in a replication cohort (STAR*D, N = 1,878). Finally, a cross-trait GWAS meta-analysis was performed by combining summary statistics. We show that the PGSs for CAD and obesity were inversely associated with SSRIs treatment response. At the most significant thresholds, the PGS for CAD and body mass index accounted 1.3%, and 0.8% of the observed variability in treatment response to SSRIs, respectively. In the cross-trait meta-analyses, we identified (1) 14 genetic loci (including NEGR1, CADM2, PMAIP1, PARK2) that are associated with both obesity and SSRIs treatment response; (2) five genetic loci (LINC01412, PHACTR1, CDKN2B, ATXN2, KCNE2) with effects on CAD and SSRIs treatment response. Our findings implicate that the genetic variants of CAD and obesity are linked to SSRIs treatment response in MDD. A better SSRIs treatment response might be achieved through a stratified allocation of treatment for MDD patients with a genetic risk for obesity or CAD.

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Title: The association of obesity and coronary artery disease genes with response to SSRIs treatment in major depression
Authors: Azmeraw T. Amare
Klaus Oliver Schubert
Fasil Tekola-Ayele
Yi-Hsiang Hsu
Katrin Sangkuhl
Gregory Jenkins
Ryan M. Whaley
Poulami Barman
Anthony Batzler
Russ B. Altman
Volker Arolt
Jürgen Brockmöller
Chia-Hui Chen
Katharina Domschke
Daniel K. Hall-Flavin
Chen-Jee Hong
Ari Illi
Yuan Ji
Olli Kampman
Toshihiko Kinoshita
Esa Leinonen
Ying-Jay Liou
Taisei Mushiroda
Shinpei Nonen
Michelle K. Skime
Liewei Wang
Masaki Kato
Yu-Li Liu
Verayuth Praphanphoj
Julia C. Stingl
William V. Bobo
Shih-Jen Tsai
Michiaki Kubo
Teri E. Klein
Richard M. Weinshilboum
Joanna M. Biernacka
Bernhard T. Baune
Publication date: 01-01-2019
Publisher: Springer Vienna
Keywords: Obesity
Antidepressant Drugs
Obesity
Affective Disorder
Affective Disorder
Arterial Diseases
Antidepressant Drugs
Published in: Journal of Neural Transmission / Issue 1/2019
Print ISSN: 0300-9564
Electronic ISSN: 1435-1463
DOI: https://doi.org/10.1007/s00702-018-01966-x

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The association of obesity and coronary artery disease genes with response to SSRIs treatment in major depression

Abstract

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Abstract

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