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van der Spek, A.* ; Stewart, I.D.* ; Kühnel, B. ; Pietzner, M.* ; Alshehri, T.* ; Gauß, F.* ; Hysi, P.G.* ; MahmoudianDehkordi, S.* ; Heinken, A.* ; Luik, A.I.* ; Ladwig, K.-H. ; Kastenmüller, G. ; Menni, C.* ; Hertel, J.* ; Ikram, M.A.* ; de Mutsert, R.* ; Suhre, K.* ; Gieger, C. ; Strauch, K. ; Völzke, H.* ; Meitinger, T. ; Mangino, M.* ; Flaquer, A. ; Waldenberger, M. ; Peters, A. ; Thiele, I.* ; Kaddurah-Daouk, R.* ; Dunlop, B.W.* ; Rosendaal, F.R.* ; Wareham, N.J.* ; Spector, T.D.* ; Kunze, S. ; Grabe, H.J.* ; Mook-Kanamori, D.O.* ; Langenberg, C.* ; van Duijn, C.M.* ; Amin, N.*

Circulating metabolites modulated by diet are associated with depression.

Mol. Psychiatry 28, 3874-3887 (2023)
Publ. Version/Full Text DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
Metabolome reflects the interplay of genome and exposome at molecular level and thus can provide deep insights into the pathogenesis of a complex disease like major depression. To identify metabolites associated with depression we performed a metabolome-wide association analysis in 13,596 participants from five European population-based cohorts characterized for depression, and circulating metabolites using ultra high-performance liquid chromatography/tandem accurate mass spectrometry (UHPLC/MS/MS) based Metabolon platform. We tested 806 metabolites covering a wide range of biochemical processes including those involved in lipid, amino-acid, energy, carbohydrate, xenobiotic and vitamin metabolism for their association with depression. In a conservative model adjusting for life style factors and cardiovascular and antidepressant medication use we identified 8 metabolites, including 6 novel, significantly associated with depression. In individuals with depression, increased levels of retinol (vitamin A), 1-palmitoyl-2-palmitoleoyl-GPC (16:0/16:1) (lecithin) and mannitol/sorbitol and lower levels of hippurate, 4-hydroxycoumarin, 2-aminooctanoate (alpha-aminocaprylic acid), 10-undecenoate (11:1n1) (undecylenic acid), 1-linoleoyl-GPA (18:2) (lysophosphatidic acid; LPA 18:2) are observed. These metabolites are either directly food derived or are products of host and gut microbial metabolism of food-derived products. Our Mendelian randomization analysis suggests that low hippurate levels may be in the causal pathway leading towards depression. Our findings highlight putative actionable targets for depression prevention that are easily modifiable through diet interventions.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Major Depression; Nervous-system; Retinoic Acid; Lipid-metabolism; Brain; Acetylcholine; Arginine; Ceramide; Susceptibility; Metabolomics
ISSN (print) / ISBN 1359-4184
e-ISSN 1476-5578
Journal Molecular Psychiatry
Quellenangaben Volume: 28, Issue: 9, Pages: 3874-3887 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Publishing Place Campus, 4 Crinan St, London, N1 9xw, England
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Epidemiology II (EPI2)
Institute of Computational Biology (ICB)
Institute of Genetic Epidemiology (IGE)
Institute of Human Genetics (IHG)
Grants Netherlands Organization for the Health Research and Development (ZonMw)
Research Institute for Diseases in the Elderly (RIDE)
Ministry of Education, Culture and Science
Ministry for Health, Welfare and Sports
European Commission (DG XII)
Municipality of Rotterdam
Netherlands Genomics Initiative (NGI)/Netherlands Organisation for Scientific Research (NWO) sponsored Netherlands Consortium for Healthy Aging (NCHA)
Genetic Laboratory of the Department of Internal Medicine, Erasmus MC
Complementation Project of the Biobanking and Biomolecular Research Infrastructure Netherlands (BBMRI-NL)
German Federal Ministry of Education and Research (BMBF)
Ministry for Education, Research and Cultural Affairs, as well as the Ministry of Social Affairs of the Federal State of Mecklenburg-West Pomerania
Greifswald Approach to Individualized Medicine (GANI_MED)
Federal Ministry of Education and Research
Ministry of Cultural Affairs of the Federal State of Mecklenburg-West Pomerania
German Research Foundation (DFG)
Erasmus Medical Center and Erasmus University, Rotterdam
State of Bavaria
Munich Center of Health Sciences (MC-Health), Ludwig-Maximilians-Universitaet, as part of LMUinnovativ
Biomedical Research Program at Weill Cornell Medicine in Qatar - Qatar Foundation
Medical Research Council
Cancer Research UK
MRC Cambridge Initiative in Metabolic Science
Innovative Medicines Initiative Joint Undertaking under EMIF
Division and the Board of Directors of the Leiden University Medical Centre
Leiden University, Research Profile Area Vascular and Regenerative Medicine'
Dutch Science Organization (ZonMW-VENI )
National Institute of Mental Health (NIMH)
Intervention Development and Applied Research (CIDAR)
Helmholtz Zentrum Muenchen - German Research Center for Environmental Health