Metabolomics Profile in Depression: A Pooled Analysis of 230 Metabolic Markers in 5283 Cases With Depression and 10,145 Controls

BBMRI-NL Metabolomics Consortium, Mariska Bot, Yuri Milaneschi, Tahani Al-Shehri, Najaf Amin, Sanzhima Garmaeva, Gerrit L J Onderwater, Rene Pool, Carisha S Thesing, Lisanne S Vijfhuizen, Nicole Vogelzangs, Ilja C W Arts, Ayse Demirkan, Cornelia van Duijn, Marleen van Greevenbroek, Carla J H van der Kallen, Sebastian Köhler, Lannie Ligthart, Arn M J M van den Maagdenberg, Dennis O Mook-KanamoriRenée de Mutsert, Henning Tiemeier, Miranda T Schram, Coen D A Stehouwer, Gisela M Terwindt, Ko Willems van Dijk, Jingyuan Fu, Alexandra Zhernakova, Marian Beekman, P Eline Slagboom, Dorret I Boomsma, Brenda W J H Penninx

OnderzoeksoutputAcademicpeer review

28 Citaten (Scopus)


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 A1 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.

Originele taal-2English
Pagina's (van-tot)409-418
Aantal pagina's10
TijdschriftBiological Psychiatry
Nummer van het tijdschrift5
StatusPublished - 1-mrt-2020

Citeer dit