Associations of depression status with plasma levels of candidate lipid and amino acid metabolites: a meta-analysis of individual data from three independent samples of US postmenopausal women - PubMed (original) (raw)

Meta-Analysis

Associations of depression status with plasma levels of candidate lipid and amino acid metabolites: a meta-analysis of individual data from three independent samples of US postmenopausal women

Tianyi Huang et al. Mol Psychiatry. 2021 Jul.

Abstract

Recent animal and small clinical studies have suggested depression is related to altered lipid and amino acid profiles. However, this has not been examined in a population-based sample, particularly in women. We identified multiple metabolites associated with depression as potential candidates from prior studies. Cross-sectional data from three independent samples of postmenopausal women were analyzed, including women from the Women's Health Initiative-Observational Study (WHI-OS, n = 926), the WHI-Hormone Trials (WHI-HT; n = 1,325), and the Nurses' Health Study II Mind-Body Study (NHSII-MBS; n = 218). Positive depression status was defined as having any of the following: elevated depressive symptoms, antidepressant use, or depression history. Plasma metabolites were measured using liquid chromatography-tandem mass spectrometry (21 phosphatidylcholines (PCs), 7 lysophosphatidylethanolamines, 5 ceramides, 3 branched chain amino acids, and 9 neurotransmitters). Associations between depression status and metabolites were evaluated using multivariable linear regression; results were pooled by random-effects meta-analysis with multiple testing adjustment using the false discovery rate (FDR). Prevalence rates of positive depression status were 24.4% (WHI-OS), 25.7% (WHI-HT), and 44.7% (NHSII-MBS). After multivariable adjustment, positive depression status was associated with higher levels of glutamate and PC 36 : 1/38 : 3, and lower levels of tryptophan and GABA-to-glutamate and GABA-to-glutamine ratio (FDR-p < 0.05). Positive associations with LPE 18 : 0/18 : 1 and inverse associations with valine and serotonin were also observed, although these associations did not survive FDR adjustment. Associations of positive depression status with several candidate metabolites including PC 36 : 1/38 : 3 and amino acids involved in neurotransmission suggest potential depression-related metabolic alterations in postmenopausal women, with possible implications for later chronic disease.

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Figures

Figure 1.

Associations of depression status (defined as the presence of any of elevated current depressive symptoms, history of depression or antidepressant use) with plasma lipids, including phosphatidylcholines (PC), lysophosphatidylethanolamines (LPE) and ceramides (CER), adjusted for age, race/ethnicity, BMI, hypertension, diabetes, aspirin use, statin use, other lipid-lowering medications and hormone therapy. P: nominal p-value; Bold: FDR-p<0.05

Figure 2.

Associations of depression status (defined as the presence of any of elevated current depressive symptoms, history of depression or antidepressant use) with branched-chain amino acids and amino acid neurotransmitters in plasma, adjusted for age, race/ethnicity, BMI, hypertension, diabetes, aspirin use, statin use, other lipid-lowering medications and hormone therapy. P: nominal p-value; Bold: FDR-p<0.05 Abbreviations: GABA: γ-aminobutyric acid; Glu: glutamate; Gln: glutamine; Gly: glycine; His: histidine; Ile: isoleucine; Leu: leucine; Phe: phenylalanine; 5-HT: serotonin; Trp: tryptophan; Tyr: tyrosine; Val: valine.

Figure 3.

Pooled associations of depression characteristics with plasma lipid and amino acid metabolites identified in the primary analyses, adjusted for age, race/ethnicity, BMI, hypertension, diabetes, aspirin use, statin use, other lipid-lowering medications and hormone therapy. (a) Associations with current and past depression. Participants were categorized into three groups - past depression (defined as history of depression without current depressive symptoms or current antidepressant use), current depression (defined as current elevated depressive symptoms or current antidepressant use regardless of depression history) and those with no evidence of depression (no current depressive symptoms, no antidepressant use, and no depression history). The reference group included women with no evidence of depression. (b) Associations with depression status by antidepressant use. Participants were categorized into four groups – (1) presence of current depressive symptoms or history of depression with antidepressant use; (2) presence of current depressive symptoms or history of depression without antidepressant use; (3) antidepressant use with neither current depressive symptoms nor history of depression; and (4) no current depressive symptoms, history of depression or antidepressant use (reference). P: nominal p-value; Bold: FDR-p<0.05 Abbreviations: GABA: γ-aminobutyric acid; Glu: glutamate; Gln: glutamine; 5-HT: serotonin; Trp: tryptophan; Val: valine.

Figure 3.

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Associations of depression status with plasma levels of candidate lipid and amino acid metabolites: a meta-analysis of individual data from three independent samples of US postmenopausal women - PubMed (original) (raw)