TY - JOUR
T1 - Metabolomics Profile in Depression: A Pooled Analysis of 230 Metabolic Markers in 5283 Cases With Depression and 10,145 Controls
AU - Bot, Mariska
AU - Milaneschi, Yuri
AU - Al-Shehri, Tahani
AU - Amin, Najaf
AU - Garmaeva, Sanzhima
AU - Onderwater, G.L.J.
AU - Pool, R.
AU - Thesing, Carisha S.
AU - Vijfhuizen, Lisanne S.
AU - Vogelzangs, Nicole
AU - Arts, Ilja C.W.
AU - Demirkan, Ayse
AU - van Duijn, Cornelia
AU - van Greevenbroek, Marleen
AU - van der Kallen, Carla J.H.
AU - Köhler, Sebastian
AU - Ligthart, Lannie
AU - van den Maagdenberg, Arn M.J.M.
AU - Mook-Kanamori, Dennis O.
AU - de Mutsert, Renée
AU - Tiemeier, Henning
AU - Schram, Miranda T.
AU - Stehouwer, Coen D.A.
AU - Terwindt, Gisela M.
AU - Willems van Dijk, Ko
AU - Fu, Jingyuan
AU - Zhernakova, Alexandra
AU - Beekman, Marian
AU - Slagboom, Eline
AU - Boomsma, Dorret I.
AU - Penninx, Brenda W.J.H.
AU - Beekman, M.
AU - Suchiman, H.E.D.
AU - Deelen, J.
AU - Amin, N.
AU - Beulens, J.W.
AU - van der Bom, J.A.
AU - Bomer, N.
AU - Demirkan, A.
AU - van Hilten, J.A.
AU - Meessen, J.M.T.A.
AU - Pool, R.
AU - Moed, M.H.
AU - Fu, J.
AU - Onderwater, G.L.J.
AU - Rutters, F.
AU - van der Heijden, A.A.W.A.
AU - van der Spek, A.
AU - Geleijnse, J.M.
AU - Jukema, J.W.
PY - 2020/3/1
Y1 - 2020/3/1
N2 - 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.
AB - 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.
KW - Biomarkers
KW - Cardiovascular
KW - Depression
KW - Metabolites
KW - Metabolomics
KW - Pooled analysis
U2 - 10.1016/j.biopsych.2019.08.016
DO - 10.1016/j.biopsych.2019.08.016
M3 - Article
C2 - 31635762
AN - SCOPUS:85073832826
SN - 0006-3223
VL - 87
SP - 409
EP - 418
JO - Biological Psychiatry
JF - Biological Psychiatry
IS - 5
ER -