Metabolomics and Self-Reported Depression, Anxiety, and Phobic Symptoms in the VA Normative Aging Study

Abstract

Traditional approaches to understanding metabolomics in mental illness have focused on investigating a single disorder or comparisons between diagnoses, but a growing body of evidence suggests substantial mechanistic overlap in mental disorders that could be reflected by the metabolome. In this study, we investigated associations between global plasma metabolites and abnormal scores on the depression, anxiety, and phobic anxiety subscales of the Brief Symptom Inventory (BSI) among 405 older males who participated in the Normative Aging Study (NAS). Our analysis revealed overlapping and distinct metabolites associated with each mental health dimension subscale and four metabolites belonging to xenobiotic, carbohydrate, and amino acid classes that were consistently associated across all three symptom dimension subscales. Furthermore, three of these four metabolites demonstrated a higher degree of alteration in men who reported poor scores in all three dimensions compared to men with poor scores in only one, suggesting the potential for shared underlying biology but a differing degree of perturbation when depression and anxiety symptoms co-occur. Our findings implicate pathways of interest relevant to the overlap of mental health conditions in aging veterans and could represent clinically translatable targets underlying poor mental health in this high-risk population.

Keywords: anxiety; brief symptom inventory (BSI); depression; mental health; metabolomics; normative aging study (NAS); phobic anxiety; veterans.

Figure 1

Overlap of NAS men with abnormal scores (i.e., one standard deviation above the sample mean) on the depression, anxiety, and phobic anxiety BSI subscales. In the lower left panel, the total number of men identified as having abnormal scores on each subscale is shown.

Figure 2

Summary of significant metabolite associations and abnormal scores on each BSI subscale colored according to the chemical class of the metabolite. (A) The volcano plots summarize the associations between the metabolites and each BSI subscale; the metabolites above the dotted black line met a nominal p < 0.05 threshold for associations with score. Metabolites belonging to sub-pathways common to abnormal scores across multiple subscales are labeled. (B) A Venn diagram depicts the overlap in the nominally significant metabolites at p < 0.05 for each of the three BSI subscales.