Circulating metabolites modulated by diet are associated with depression

Area of Science:

• Metabolomics
• Psychiatry
• Nutritional Science

Background:

• The metabolome offers insights into complex diseases like major depression by reflecting genome-exposome interactions.
• Understanding molecular pathways is crucial for identifying depression pathogenesis.

Purpose of the Study:

• To identify specific metabolites associated with major depression.
• To explore potential causal links and targets for depression prevention through diet.

Main Methods:

• Conducted a metabolome-wide association analysis in 13,596 participants across five European cohorts.
• Utilized ultra-high-performance liquid chromatography/tandem mass spectrometry (UHPLC/MS/MS) to analyze 806 circulating metabolites.
• Employed Mendelian randomization to investigate causal relationships between metabolites and depression.

Main Results:

• Identified eight metabolites significantly associated with depression, six of which are novel.
• Observed increased levels of retinol, lecithin, and mannitol/sorbitol, and decreased levels of hippurate, 4-hydroxycoumarin, 2-aminooctanoate, 10-undecenoate, and lysophosphatidic acid (LPA 18:2) in individuals with depression.
• Mendelian randomization suggested a potential causal role for low hippurate levels in depression development.

Conclusions:

• Metabolite profiles, influenced by diet and gut microbiota, are significantly associated with major depression.
• Low hippurate levels may be causally linked to depression.
• Findings indicate potential dietary targets for depression prevention and management.