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Zacharias, H.U.* ; Hertel, J.* ; Johar, H. ; Pietzner, M.* ; Lukaschek, K.* ; Atasoy, S.* ; Kunze, S. ; Völzke, H.* ; Nauck, M.* ; Friedrich, N.* ; Kastenmüller, G. ; Grabe, H.J.* ; Gieger, C. ; Krumsiek, J. ; Ladwig, K.-H.

A metabolome-wide association study in the general population reveals decreased levels of serum laurylcarnitine in people with depression.

Mol. Psychiatry, DOI: 10.1038/s41380-021-01176-0 (2021)
Publ. Version/Full Text DOI
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
Depression constitutes a leading cause of disability worldwide. Despite extensive research on its interaction with psychobiological factors, associated pathways are far from being elucidated. Metabolomics, assessing the final products of complex biochemical reactions, has emerged as a valuable tool for exploring molecular pathways. We conducted a metabolome-wide association analysis to investigate the link between the serum metabolome and depressed mood (DM) in 1411 participants of the KORA (Cooperative Health Research in the Augsburg Region) F4 study (discovery cohort). Serum metabolomics data comprised 353 unique metabolites measured by Metabolon. We identified 72 (5.1%) KORA participants with DM. Linear regression tests were conducted modeling each metabolite value by DM status, adjusted for age, sex, body-mass index, antihypertensive, cardiovascular, antidiabetic, and thyroid gland hormone drugs, corticoids and antidepressants. Sensitivity analyses were performed in subcohorts stratified for sex, suicidal ideation, and use of antidepressants. We replicated our results in an independent sample of 968 participants of the SHIP-Trend (Study of Health in Pomerania) study including 52 (5.4%) individuals with DM (replication cohort). We found significantly lower laurylcarnitine levels in KORA F4 participants with DM after multiple testing correction according to Benjamini/Hochberg. This finding was replicated in the independent SHIP-Trend study. Laurylcarnitine remained significantly associated (p value < 0.05) with depression in samples stratified for sex, suicidal ideation, and antidepressant medication. Decreased blood laurylcarnitine levels in depressed individuals may point to impaired fatty acid oxidation and/or mitochondrial function in depressive disorders, possibly representing a novel therapeutic target.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Acetyl-l-carnitine; Mitochondrial-function; Kynurenine Pathway; Cohort Profile; Disorder; Anxiety; Dysfunction; Validation; Biomarkers; Increases
ISSN (print) / ISBN 1359-4184
e-ISSN 1476-5578
Publisher Nature Publishing Group
Publishing Place Campus, 4 Crinan St, London, N1 9xw, England
Reviewing status Peer reviewed
Grants German Federal State of Mecklenburg-West Pomerania
BMBF
State of Bavaria
German Research Center for Environmental Health - German Federal Ministry of Education and Research (BMBF)
Helmholtz Zentrum Munchen