Genetic Association of Major Depression With Atypical Features and Obesity-Related Immunometabolic Dysregulations.

Details

Serval ID
serval:BIB_EB9A137C0943
Type
Article: article from journal or magazin.
Collection
Publications
Title
Genetic Association of Major Depression With Atypical Features and Obesity-Related Immunometabolic Dysregulations.
Journal
JAMA psychiatry
Author(s)
Milaneschi Y., Lamers F., Peyrot W.J., Baune B.T., Breen G., Dehghan A., Forstner A.J., Grabe H.J., Homuth G., Kan C., Lewis C., Mullins N., Nauck M., Pistis G., Preisig M., Rivera M., Rietschel M., Streit F., Strohmaier J., Teumer A., Van der Auwera S., Wray N.R., Boomsma D.I., Penninx BWJH
Working group(s)
CHARGE Inflammation Working Group and the Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium
ISSN
2168-6238 (Electronic)
ISSN-L
2168-622X
Publication state
Published
Issued date
01/12/2017
Peer-reviewed
Oui
Volume
74
Number
12
Pages
1214-1225
Language
english
Notes
Publication types: Journal Article ; Multicenter Study
Publication Status: ppublish
Abstract
The association between major depressive disorder (MDD) and obesity may stem from shared immunometabolic mechanisms particularly evident in MDD with atypical features, characterized by increased appetite and/or weight (A/W) during an active episode.
To determine whether subgroups of patients with MDD stratified according to the A/W criterion had a different degree of genetic overlap with obesity-related traits (body mass index [BMI] and levels of C-reactive protein [CRP] and leptin).
This multicenter study assembled genome-wide genotypic and phenotypic measures from 14 data sets of the Psychiatric Genomics Consortium. Data sets were drawn from case-control, cohort, and population-based studies, including 26 628 participants with established psychiatric diagnoses and genome-wide genotype data. Data on BMI were available for 15 237 participants. Data were retrieved and analyzed from September 28, 2015, through May 20, 2017.
Lifetime DSM-IV MDD was diagnosed using structured diagnostic instruments. Patients with MDD were stratified into subgroups according to change in the DSM-IV A/W symptoms as decreased or increased.
Data included 11 837 participants with MDD and 14 791 control individuals, for a total of 26 628 participants (59.1% female and 40.9% male). Among participants with MDD, 5347 (45.2%) were classified in the decreased A/W and 1871 (15.8%) in the increased A/W subgroups. Common genetic variants explained approximately 10% of the heritability in the 2 subgroups. The increased A/W subgroup showed a strong and positive genetic correlation (SE) with BMI (0.53 [0.15]; P = 6.3 × 10-4), whereas the decreased A/W subgroup showed an inverse correlation (-0.28 [0.14]; P = .06). Furthermore, the decreased A/W subgroup had a higher polygenic risk for increased BMI (odds ratio [OR], 1.18; 95% CI, 1.12-1.25; P = 1.6 × 10-10) and levels of CRP (OR, 1.08; 95% CI, 1.02-1.13; P = 7.3 × 10-3) and leptin (OR, 1.09; 95% CI, 1.06-1.12; P = 1.7 × 10-3).
The phenotypic associations between atypical depressive symptoms and obesity-related traits may arise from shared pathophysiologic mechanisms in patients with MDD. Development of treatments effectively targeting immunometabolic dysregulations may benefit patients with depression and obesity, both syndromes with important disability.

Keywords
Adult, Body Mass Index, C-Reactive Protein/analysis, Craving, Depressive Disorder, Major/diagnosis, Depressive Disorder, Major/genetics, Depressive Disorder, Major/immunology, Depressive Disorder, Major/metabolism, Diagnostic and Statistical Manual of Mental Disorders, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, International Cooperation, Male, Obesity/diagnosis, Obesity/genetics, Obesity/psychology, Psychiatric Status Rating Scales, Weight Gain
Pubmed
Web of science
Open Access
Yes
Create date
30/10/2017 11:51
Last modification date
20/08/2019 17:13
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