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. 2022 Sep 30:16:935858.
doi: 10.3389/fnins.2022.935858. eCollection 2022.

Branched-chain amino acids linked to depression in young adults

Alyce M Whipp  1   2 , Marja Heinonen-Guzejev  2 , Kirsi H Pietiläinen  3   4 , Irene van Kamp  5 , Jaakko Kaprio  1   2
Affiliations

Branched-chain amino acids linked to depression in young adults

Alyce M Whipp et al. Front Neurosci. .

Abstract

Depression is a heterogeneous mental health problem affecting millions worldwide, but a majority of individuals with depression do not experience relief from initial treatments. Therefore, we need to improve our understanding of the biology of depression. Metabolomic approaches, especially untargeted ones, can suggest new hypotheses for further exploring biological mechanisms. Using the FinnTwin12 cohort, a longitudinal Finnish population-based twin cohort, with data collected in adolescence and young adulthood including 725 blood plasma samples, we investigated associations between depression and 11 low-molecular weight metabolites (amino acids and ketone bodies). In linear regression models with the metabolite (measured at age 22) as the dependent variable and depression ratings (measured at age 12, 14, 17, or 22 from multiple raters) as independent variables [adjusted first for age, sex, body mass index (BMI), and additional covariates (later)], we initially identified a significant negative association of valine with depression. Upon further analyses, valine remained significantly negatively associated with depression cross-sectionally and over time [meta-analysis beta = -13.86, 95% CI (-18.48 to -9.25)]. Analyses of the other branched-chain amino acids showed a significant negative association of leucine with depression [meta-analysis beta = -9.24, 95% CI (-14.53 to -3.95)], while no association was observed between isoleucine and depression [meta-analysis beta = -0.95, 95% CI (-6.00 to 4.11)]. These exploratory epidemiologic findings support further investigations into the role of branched-chain amino acids in depression.

Keywords: biomarkers; branched-chain amino acid; depression; leucine; valine; young adult mental health.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer RP declared a past collaboration with the author to the handling editor.

Figures

FIGURE 1
FIGURE 1
Overview of models and results from all depressive symptoms and p factor model analyses. BMI, body mass index; GBI, General Behavior Inventory; MET, Metabolic Equivalent of Task; MPNI, Multidimensional Peer Nomination Inventory.
FIGURE 2
FIGURE 2
Forest plot of BCAA models with standardized depressive symptom scores from different instruments, raters, and ages (with age, sex, and BMI as covariates), and meta-analysis of all models for each BCAA biomarker. BCAA, branched-chain amino acid; CI, confidence interval; GBI, General Behavior Inventory; MPNI, Multidimensional Peer Nomination Inventory.
FIGURE 3
FIGURE 3
Forest plot of BCAA models with standardized depressive symptom scores from different instruments, raters, and ages (with age and sex as covariates, BMI removed), and meta-analysis of all models for each BCAA biomarker. BCAA, branched-chain amino acid; CI, confidence interval; GBI, General Behavior Inventory; MPNI, Multidimensional Peer Nomination Inventory.
FIGURE 4
FIGURE 4
Forest plot of 3-hydroxybutyrate models with standardized p factor scores from different raters and ages (with age, sex, and BMI as covariates), as well as meta-analysis of all models. CI, confidence interval; MPNI, Multidimensional Peer Nomination Inventory.
See this image and copyright information in PMC

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