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

doi:10.1016/j.biopsych.2019.08.016

Meta-Analysis

. 2020 Mar 1;87(5):409-418.

doi: 10.1016/j.biopsych.2019.08.016. Epub 2019 Aug 29.

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

Mariska Bot¹, Yuri Milaneschi², Tahani Al-Shehri³, Najaf Amin⁴, Sanzhima Garmaeva⁵, Gerrit L J Onderwater⁶, Rene Pool⁷, Carisha S Thesing², Lisanne S Vijfhuizen⁸, Nicole Vogelzangs⁹, Ilja C W Arts¹⁰, Ayse Demirkan¹¹, Cornelia van Duijn⁴, Marleen van Greevenbroek¹², Carla J H van der Kallen¹², Sebastian Köhler¹³, Lannie Ligthart⁷, Arn M J M van den Maagdenberg¹⁴, Dennis O Mook-Kanamori³, Renée de Mutsert³, Henning Tiemeier⁴, Miranda T Schram¹², Coen D A Stehouwer¹², Gisela M Terwindt⁶, Ko Willems van Dijk¹⁵, Jingyuan Fu¹⁶, Alexandra Zhernakova⁵, Marian Beekman¹⁷, P Eline Slagboom¹⁷, Dorret I Boomsma⁷, Brenda W J H Penninx²; BBMRI-NL Metabolomics Consortium

Collaborators, Affiliations

Collaborators

BBMRI-NL Metabolomics Consortium:
M Beekman, H E D Suchiman, J Deelen, N Amin, J W Beulens, J A van der Bom, N Bomer, A Demirkan, J A van Hilten, J M T A Meessen, R Pool, M H Moed, J Fu, G L J Onderwater, F Rutters, C So-Osman, W M van der Flier, A A W A van der Heijden, A van der Spek, F W Asselbergs, E Boersma, P M Elders, J M Geleijnse, M A Ikram, M Kloppenburg, I Meulenbelt, S P Mooijaart, R G H H Nelissen, M G Netea, B W J H Penninx, C D A Stehouwer, C E Teunissen, G M Terwindt, L M 't Hart, A M J M van den Maagdenberg, P van der Harst, I C C van der Horst, C J H van der Kallen, M M J van Greevenbroek, W E van Spil, C Wijmenga, A H Zwinderman, A Zhernikova, J W Jukema, N Sattar

Affiliations

¹ Department of Psychiatry, Amsterdam Public Health Research Institute and Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit, Amsterdam, The Netherlands. Electronic address: m.bot@ggzingeest.nl.
² Department of Psychiatry, Amsterdam Public Health Research Institute and Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit, Amsterdam, The Netherlands.
³ Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
⁴ Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands.
⁵ Department of Genetics, University Medical Center Groningen, Groningen, The Netherlands.
⁶ Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands.
⁷ Department of Biological Psychology, Amsterdam Public Health Research Institute, Vrije Universiteit, Amsterdam, The Netherlands.
⁸ Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
⁹ Department of Epidemiology, Maastricht University, Maastricht, The Netherlands; Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands; Maastricht Center for Systems Biology, Maastricht University, Maastricht, The Netherlands.
¹⁰ Department of Epidemiology, Maastricht University, Maastricht, The Netherlands; Department of Internal Medicine, Maastricht University, Maastricht, The Netherlands; Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands; Maastricht Center for Systems Biology, Maastricht University, Maastricht, The Netherlands.
¹¹ Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands; Department of Human Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands.
¹² Department of Internal Medicine, Maastricht University, Maastricht, The Netherlands; Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands.
¹³ Department of Psychiatry and Neuropsychology, Maastricht University, Maastricht, The Netherlands; School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands.
¹⁴ Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands; Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
¹⁵ Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands; Department of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands.
¹⁶ Department of Genetics, University Medical Center Groningen, Groningen, The Netherlands; Department of Pediatrics, University Medical Center Groningen, Groningen, The Netherlands.
¹⁷ Department of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.

PMID: 31635762
DOI: 10.1016/j.biopsych.2019.08.016

Meta-Analysis

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

Mariska Bot et al. Biol Psychiatry. 2020.

. 2020 Mar 1;87(5):409-418.

doi: 10.1016/j.biopsych.2019.08.016. Epub 2019 Aug 29.

Authors

Collaborators

BBMRI-NL Metabolomics Consortium:
M Beekman, H E D Suchiman, J Deelen, N Amin, J W Beulens, J A van der Bom, N Bomer, A Demirkan, J A van Hilten, J M T A Meessen, R Pool, M H Moed, J Fu, G L J Onderwater, F Rutters, C So-Osman, W M van der Flier, A A W A van der Heijden, A van der Spek, F W Asselbergs, E Boersma, P M Elders, J M Geleijnse, M A Ikram, M Kloppenburg, I Meulenbelt, S P Mooijaart, R G H H Nelissen, M G Netea, B W J H Penninx, C D A Stehouwer, C E Teunissen, G M Terwindt, L M 't Hart, A M J M van den Maagdenberg, P van der Harst, I C C van der Horst, C J H van der Kallen, M M J van Greevenbroek, W E van Spil, C Wijmenga, A H Zwinderman, A Zhernikova, J W Jukema, N Sattar

Affiliations

¹ Department of Psychiatry, Amsterdam Public Health Research Institute and Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit, Amsterdam, The Netherlands. Electronic address: m.bot@ggzingeest.nl.
² Department of Psychiatry, Amsterdam Public Health Research Institute and Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit, Amsterdam, The Netherlands.
³ Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
⁴ Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands.
⁵ Department of Genetics, University Medical Center Groningen, Groningen, The Netherlands.
⁶ Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands.
⁷ Department of Biological Psychology, Amsterdam Public Health Research Institute, Vrije Universiteit, Amsterdam, The Netherlands.
⁸ Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
⁹ Department of Epidemiology, Maastricht University, Maastricht, The Netherlands; Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands; Maastricht Center for Systems Biology, Maastricht University, Maastricht, The Netherlands.
¹⁰ Department of Epidemiology, Maastricht University, Maastricht, The Netherlands; Department of Internal Medicine, Maastricht University, Maastricht, The Netherlands; Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands; Maastricht Center for Systems Biology, Maastricht University, Maastricht, The Netherlands.
¹¹ Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands; Department of Human Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands.
¹² Department of Internal Medicine, Maastricht University, Maastricht, The Netherlands; Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands.
¹³ Department of Psychiatry and Neuropsychology, Maastricht University, Maastricht, The Netherlands; School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands.
¹⁴ Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands; Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
¹⁵ Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands; Department of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands.
¹⁶ Department of Genetics, University Medical Center Groningen, Groningen, The Netherlands; Department of Pediatrics, University Medical Center Groningen, Groningen, The Netherlands.
¹⁷ Department of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.

PMID: 31635762
DOI: 10.1016/j.biopsych.2019.08.016

Abstract

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.

Keywords: Biomarkers; Cardiovascular; Depression; Metabolites; Metabolomics; Pooled analysis.

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

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

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