Journal
BIOLOGICAL PSYCHIATRY
Volume 87, Issue 5, Pages 409-418Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.biopsych.2019.08.016
Keywords
Biomarkers; Cardiovascular; Depression; Metabolites; Metabolomics; Pooled analysis
Categories
Funding
- BBMRI-NL - Dutch government through Netherlands Organisation for Scientific Research (NWO) [184.021.007, 184033111]
- Geestkracht program of the Netherlands Organisation for Health Research and Development [10-000-1002]
- VU University Medical Center
- GGZ inGeest
- Leiden University Medical Center
- Leiden University
- GGZ Rivierduinen
- University Medical Center Groningen
- University of Groningen
- Lentis
- GGZ Friesland
- GGZ Drenthe
- Rob Giel Onderzoekscentrum
- NWO [940-35-034, 480-15-001/674, 047.017.043, 016.178.056, 864.13.013]
- Dutch Diabetes Research Foundation [98.901]
- Maastricht University Medical Center+
- Netherlands Organisation for Health Research and Development [91711319]
- Centre for Medical Systems Biology
- Netherlands Consortium for Systems Biology
- Seventh Framework Programme EU project EUROHEADPAIN [602633]
- Leiden University, Research Profile Area Vascular and Regenerative Medicine
- Dutch Science Organization (ZonMW-VENI) [916.14.023]
- European Regional Development Fund via OP-Zuid
- Province of Limburg
- Dutch Ministry of Economic Affairs [31O.041]
- Stichting De Weijerhorst
- Pearl String Initiative Diabetes
- Cardiovascular Center
- Cardiovascular Research Institute Maastricht
- School for Public Health and Primary Care
- School for Nutrition, Toxicology and Metabolism
- Stichting Annadal
- Health Foundation Limburg
- JanssenCilag B.V.
- Novo Nordisk Farma B.V.
- Sanofi-Aventis Netherlands B.V.
- NWO
- MagW/ZonMW [904-61-090, 985-10-002, 904-61-193, 480-04004, l400-05-717, Addiction-31160008, Middelgroot-911-09-032, Spinozapremie 56-464-14192]
- BBMRI-NL [184.021.007]
- European Community's Seventh Framework Programme (2007-2013) ENGAGE [HEALTH-F4-2007-201413]
- European Science Council (ERC) [230374]
- Rutgers University Cell and DNA Repository (National Institute of Mental Health) [U24 MH068457-06]
- Avera Institute
- National Institutes of Health [R01D0042157-01A, MH081802, 1RC2 MH089951]
- European Commission FP6 STRP [018947 (LSHG-CT-2006-01947)]
- European Community's Seventh Framework Programme (2007-2013) by the European Commission under the program Quality of Life and Management of the Living Resources of Fifth Framework Programme [HEALTH-F42007-201413, QLG2-CT-2002-01254]
- Russian Foundation for Basic Research [047.017.043]
- Erasmus Medical Center
- Netherlands Organisation for the Health Research and Development
- Research Institute for Diseases in the Elderly
- Ministry of Education, Culture and Science
- Ministry for Health, Welfare and Sports
- European Commission (DG XII)
- Municipality of Rotterdam
- CardioVasculair Onderzoek Nederland [2012-03]
- European Science Council [715772]
- Graduate School of Medical Sciences, University of Groningen
- Erasmus University, Rotterdam
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BACKGROUND: Depression has been associated with metabolic alterations, which adversely impact cardiometabolic health. Here, a comprehensive set of metabolic markers, predominantly lipids, was compared between depressed and nondepressed persons. METHODS: Nine Dutch cohorts were included, comprising 10,145 control subjects and 5283 persons with depression, established with diagnostic interviews or questionnaires. A proton nuclear magnetic resonance metabolomics platform provided 230 metabolite measures: 51 lipids, fatty acids, and low-molecular-weight metabolites; 98 lipid composition and particle concentration measures of lipoprotein subclasses; and 81 lipid and fatty acids ratios. For each metabolite measure, logistic regression analyses adjusted for gender, age, smoking, fasting status, and lipid-modifying medication were performed within cohort, followed by random-effects meta-analyses. RESULTS: Of the 51 lipids, fatty acids, and low-molecular-weight metabolites, 21 were significantly related to depression (false discovery rate q < .05). Higher levels of apolipoprotein B, very-low-density lipoprotein cholesterol, triglycerides, diglycerides, total and monounsaturated fatty acids, fatty acid chain length, glycoprotein acetyls, tyrosine, and isoleucine and lower levels of high-density lipoprotein cholesterol, acetate, and apolipoprotein Al were associated with increased odds of depression. Analyses of lipid composition indicators confirmed a shift toward less high-density lipoprotein and more very-low-density lipoprotein and triglyceride particles in depression. Associations appeared generally consistent across gender, age, and body mass index strata and across cohorts with depressive diagnoses versus symptoms. CONCLUSIONS: This large-scale meta-analysis indicates a clear distinctive profile of circulating lipid metabolites associated with depression, potentially opening new prevention or treatment avenues for depression and its associated cardiometabolic comorbidity.
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