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

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.

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Overview publication

Title	Metabolomics Profile in Depression: A Pooled Analysis of 230 Metabolic Markers in 5283 Cases With Depression and 10,145 Controls.
Date	March 1st, 2020
Issue name	Biological psychiatry
Issue number	v87.5:409-418
DOI	10.1016/j.biopsych.2019.08.016
PubMed	31635762
Authors	Bot M, Milaneschi Y, Al-Shehri T, Amin N, Garmaeva S, Onderwater GLJ, Pool R, Thesing CS, Vijfhuizen LS, Vogelzangs N, Arts ICW, Demirkan A, van Duijn C, van Greevenbroek M, van der Kallen CJH, Köhler S, Ligthart L, van den Maagdenberg AMJM, Mook-Kanamori DO, de Mutsert R, Tiemeier H, Schram MT, Stehouwer CDA, Terwindt GM, Willems van Dijk K, Fu J, Zhernakova A, Beekman M, Slagboom PE, Boomsma DI & Penninx BWJH
Info	BBMRI-NL Metabolomics Consortium, Beekman M, Suchiman HED, Deelen J, Amin N, Beulens JW, van der Bom JA, Bomer N, Demirkan A, van Hilten JA, Meessen JMTA, Pool R, Moed MH, Fu J, Onderwater GLJ, Rutters F, So-Osman C, van der Flier WM, van der Heijden AAWA, van der Spek A, Asselbergs FW, Boersma E, Elders PM, Geleijnse JM, Ikram MA, Kloppenburg M, Meulenbelt I, Mooijaart SP, Nelissen RGHH, Netea MG, Penninx BWJH, Stehouwer CDA, Teunissen CE, Terwindt GM, 't Hart LM, van den Maagdenberg AMJM, van der Harst P, van der Horst ICC, van der Kallen CJH, van Greevenbroek MMJ, van Spil WE, Wijmenga C, Zwinderman AH, Zhernikova A, Jukema JW, Sattar N
Keywords	Biomarkers, Cardiovascular, Depression, Metabolites, Metabolomics, Pooled analysis
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