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

Biomarkers Depression Fatty Acids Humans Metabolomics Triglycerides

Biomarkers Cardiovascular Depression Metabolites Metabolomics Pooled analysis

Journal

Biological psychiatry

ISSN: 1873-2402

Titre abrégé: Biol Psychiatry

Pays: United States

ID NLM: 0213264

Informations de publication

Date de publication:
01 03 2020

Historique:

received: 05 03 2019

revised: 19 08 2019

accepted: 19 08 2019

pubmed: 23 10 2019

medline: 7 1 2021

entrez: 23 10 2019

Statut: ppublish

Résumé

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. 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. 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. 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.

Sections du résumé

BACKGROUND

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.

Identifiants

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

pubmed: 31635762

pii: S0006-3223(19)31628-2

doi: 10.1016/j.biopsych.2019.08.016

pii:

doi:

Substances chimiques

Biomarkers 0

Fatty Acids 0

Triglycerides 0

Types de publication

Journal Article Meta-Analysis Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

Pagination

409-418

Subventions

Organisme : NIMH NIH HHS

ID : U24 MH068457

Pays : United States

Organisme : NIDA NIH HHS

ID : R01 DA042157

Pays : United States

Investigateurs

M Beekman (M)

H E D Suchiman (HED)

J Deelen (J)

N Amin (N)

J W Beulens (JW)

J A van der Bom (JA)

N Bomer (N)

A Demirkan (A)

J A van Hilten (JA)

J M T A Meessen (JMTA)

R Pool (R)

M H Moed (MH)

J Fu (J)

G L J Onderwater (GLJ)

F Rutters (F)

C So-Osman (C)

W M van der Flier (WM)

A A W A van der Heijden (AAWA)

A van der Spek (A)

F W Asselbergs (FW)

E Boersma (E)

P M Elders (PM)

J M Geleijnse (JM)

M A Ikram (MA)

M Kloppenburg (M)

I Meulenbelt (I)

S P Mooijaart (SP)

R G H H Nelissen (RGHH)

M G Netea (MG)

B W J H Penninx (BWJH)

C D A Stehouwer (CDA)

C E Teunissen (CE)

G M Terwindt (GM)

L M 't Hart (LM)

A M J M van den Maagdenberg (AMJM)

P van der Harst (P)

I C C van der Horst (ICC)

C J H van der Kallen (CJH)

M M J van Greevenbroek (MMJ)

W E van Spil (WE)

C Wijmenga (C)

A H Zwinderman (AH)

A Zhernikova (A)

J W Jukema (JW)

N Sattar (N)