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

Publication ,  Journal Article
Milaneschi, Y; Lamers, F; Peyrot, WJ; Baune, BT; Breen, G; Dehghan, A; Forstner, AJ; Grabe, HJ; Homuth, G; Kan, C; Lewis, C; Mullins, N ...
Published in: JAMA Psychiatry
December 1, 2017

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.

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Published In

JAMA Psychiatry

DOI

EISSN

2168-6238

Publication Date

December 1, 2017

Volume

74

Issue

12

Start / End Page

1214 / 1225

Location

United States

Related Subject Headings

  • Weight Gain
  • Psychiatric Status Rating Scales
  • Obesity
  • Male
  • International Cooperation
  • Humans
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease
  • Female
  • Diagnostic and Statistical Manual of Mental Disorders
 

Citation

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Milaneschi, Y., Lamers, F., Peyrot, W. J., Baune, B. T., Breen, G., Dehghan, A., … CHARGE Inflammation Working Group and the Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, . (2017). Genetic Association of Major Depression With Atypical Features and Obesity-Related Immunometabolic Dysregulations. JAMA Psychiatry, 74(12), 1214–1225. https://doi.org/10.1001/jamapsychiatry.2017.3016
Milaneschi, Yuri, Femke Lamers, Wouter J. Peyrot, Bernhard T. Baune, Gerome Breen, Abbas Dehghan, Andreas J. Forstner, et al. “Genetic Association of Major Depression With Atypical Features and Obesity-Related Immunometabolic Dysregulations.JAMA Psychiatry 74, no. 12 (December 1, 2017): 1214–25. https://doi.org/10.1001/jamapsychiatry.2017.3016.
Milaneschi Y, Lamers F, Peyrot WJ, Baune BT, Breen G, Dehghan A, et al. Genetic Association of Major Depression With Atypical Features and Obesity-Related Immunometabolic Dysregulations. JAMA Psychiatry. 2017 Dec 1;74(12):1214–25.
Milaneschi, Yuri, et al. “Genetic Association of Major Depression With Atypical Features and Obesity-Related Immunometabolic Dysregulations.JAMA Psychiatry, vol. 74, no. 12, Dec. 2017, pp. 1214–25. Pubmed, doi:10.1001/jamapsychiatry.2017.3016.
Milaneschi Y, Lamers F, Peyrot WJ, Baune BT, Breen G, Dehghan A, Forstner AJ, Grabe HJ, 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 NR, Boomsma DI, Penninx BWJH, CHARGE Inflammation Working Group and the Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium. Genetic Association of Major Depression With Atypical Features and Obesity-Related Immunometabolic Dysregulations. JAMA Psychiatry. 2017 Dec 1;74(12):1214–1225.

Published In

JAMA Psychiatry

DOI

EISSN

2168-6238

Publication Date

December 1, 2017

Volume

74

Issue

12

Start / End Page

1214 / 1225

Location

United States

Related Subject Headings

  • Weight Gain
  • Psychiatric Status Rating Scales
  • Obesity
  • Male
  • International Cooperation
  • Humans
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease
  • Female
  • Diagnostic and Statistical Manual of Mental Disorders