TY - JOUR
T1 - A metabolome-wide association study in the general population reveals decreased levels of serum laurylcarnitine in people with depression
AU - Zacharias, Helena U.
AU - Hertel, Johannes
AU - Johar, Hamimatunnisa
AU - Pietzner, Maik
AU - Lukaschek, Karoline
AU - Atasoy, Seryan
AU - Kunze, Sonja
AU - Völzke, Henry
AU - Nauck, Matthias
AU - Friedrich, Nele
AU - Kastenmüller, Gabi
AU - Grabe, Hans J.
AU - Gieger, Christian
AU - Krumsiek, Jan
AU - Ladwig, Karl-Heinz
N1 - Funding Information:
Acknowledgements The KORA research platform and the KORA Augsburg studies are financed by the Helmholtz Zentrum München, German Research Center for Environmental Health, which is funded by the German Federal Ministry of Education and Research (BMBF) and the State of Bavaria. The work of HUZ was supported by the BMBF within the framework of the e:Med research and funding concept (grant no. 01ZX1912A). The SHIP study is part of the Community Medicine Research net (CMR) (http://www.medizin.uni-greifswald.de/icm) of the University Medicine Greifswald, which is supported by the German Federal State of Mecklenburg-West Pomerania.
Funding Information:
The KORA research platform and the KORA Augsburg studies are financed by the Helmholtz Zentrum M?nchen, German Research Center for Environmental Health, which is funded by the German Federal Ministry of Education and Research (BMBF) and the State of Bavaria. The work of HUZ was supported by the BMBF within the framework of the e:Med research and funding concept (grant no. 01ZX1912A). The SHIP study is part of the Community Medicine Research net (CMR) (http://www.medizin.uni-greifswald.de/icm) of the University Medicine Greifswald, which is supported by the German Federal State of Mecklenburg-West Pomerania.
Funding Information:
Conflict of interest HJG has received travel grants and speakers honoraria from Fresenius Medical Care, Neuraxpharm, Servier, and Janssen Cilag as well as research funding from Fresenius Medical Care.
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85107424792&partnerID=8YFLogxK
U2 - 10.1038/s41380-021-01176-0
DO - 10.1038/s41380-021-01176-0
M3 - Article
C2 - 34088979
AN - SCOPUS:85107424792
SN - 1359-4184
VL - 26
SP - 7372
EP - 7383
JO - Molecular Psychiatry
JF - Molecular Psychiatry
IS - 12
ER -
