Abstract
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.
Highlights
Depression and related conditions are among the most common psychiatric disorders worldwide [1]
1411 study participants of the KORA F4 (48.5% men, 51.5% women), with a mean age of 58.6 ± 7.49 years and body-mass index (BMI) of 27.98 ± 4.79 kg/m2 were included in this study among them 72 (5.1%) participants suffering from depression
We were able to identify the organic compound laurylcarnitine to be significantly associated with depressive symptoms after thorough correction for multiple testing, and successfully replicated this finding in an independent general population sample of 968 SHIP-Trend study participants
Summary
Depression and related conditions are among the most common psychiatric disorders worldwide [1]. Characterized by profound sustained negative affectivity and reduced drive and energy [2] as its key elements, depression severely limits daily functioning and leads to substantial impairments in quality of life of affected subjects [3]. Negative life experiences and trauma, in childhood [4] and often amplified by social isolation or loneliness, contribute to depression onset. Depression is linked to a state of chronic psychosocial stress likely to affect multiple psychobiological systems with impairments of the HPA axis [5] and activation of subclinical chronic inflammation in the absence of inhibitory feedback [6] among the most prominent central pathways between the adverse mental disease condition and its physiological underpinning. A deeper understanding of signaling molecules is still in its infancy [7,8,9]
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