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

• Verfasst von: Milaneschi, Yuri [VerfasserIn]
• Verfasst von: Rietschel, Marcella [VerfasserIn]
• Verfasst von: Streit, Fabian [VerfasserIn]
• Verfasst von: Strohmaier, Jana [VerfasserIn]
• Titel: Genetic Association of Major Depression With Atypical Features and Obesity-Related Immunometabolic Dysregulations
• Verf.angabe: Yuri Milaneschi, Femke Lamers, Wouter J. Peyrot, Bernhard T. Baune, Gerome Breen, Abbas Dehghan, Andreas J. Forstner, Hans J. Grabe, Georg Homuth, Carol Kan, Cathryn Lewis, Niamh Mullins, Matthias Nauck, Giorgio Pistis, Martin Preisig, Margarita Rivera, Marcella Rietschel, Fabian Streit, Jana Strohmaier, Alexander Teumer, Sandra Van der Auwera, Naomi R. Wray, Dorret I. Boomsma, Brenda W.J.H. Penninx
• E-Jahr: 2017
• Jahr: December 2017
• Umfang: 12 S.
• Fussnoten: Gesehen am 31.10.2018
• Titel Quelle: Enthalten in: JAMA psychiatry
• Ort Quelle: Chicago, Ill. : AMA, 2013
• Jahr Quelle: 2017
• Band/Heft Quelle: 74(2017), 12, Seite 1214-1225
• ISSN Quelle: 2168-6238
• DOI: doi:10.1001/jamapsychiatry.2017.3016
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1582451907

Abstract

Importance 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.Objective 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). Design, Setting, and Patients 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. Main Outcomes and Measures 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. Results 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. Conclusions and Relevance 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.