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

Bot, Mariska; Milaneschi, Yuri; Al-Shehri, Tahani; Amin, Najaf; Garmaeva, Sanzhima; Onderwater, G.L.J.; Pool, R.; Thesing, Carisha S.; Vijfhuizen, Lisanne S.; Vogelzangs, Nicole; Arts, Ilja C.W.; Demirkan, Ayse; Duijn, Cornelia van; Greevenbroek, Marleen van; Kallen, Carla J.H. van der; Köhler, Sebastian; Ligthart, Lannie; Maagdenberg, Arn M.J.M. van den; Mook-Kanamori, Dennis O.; Mutsert, Renée de; Tiemeier, Henning; Schram, Miranda T.; Stehouwer, Coen D.A.; Terwindt, Gisela M.; Willems van Dijk, Ko; Fu, Jingyuan; Zhernakova, Alexandra; Beekman, Marian; Slagboom, Eline; Boomsma, Dorret I.; Penninx, Brenda W.J.H.; Beekman, M.; Suchiman, H.E.D.; Deelen, J.; Amin, N.; Beulens, J.W.; Bom, J.A. van der; Bomer, N.; Demirkan, A.; Hilten, J.A. van; Meessen, J.M.T.A.; Pool, R.; Moed, M.H.; Fu, J.; Onderwater, G.L.J.; Rutters, F.; Heijden, A.A.W.A. van der; Spek, A. van der; Geleijnse, J.M.; Jukema, J.W.


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.