Metabolomic profiles discriminating anxiety from depression

Abstract

Objective: Depression has been associated with metabolomic alterations. Depressive and anxiety disorders are often comorbid diagnoses and are suggested to share etiology. We investigated whether differential metabolomic alterations are present between anxiety and depressive disorders and which clinical characteristics of these disorders are related to metabolomic alterations.

Methods: Data were from the Netherlands Study of Depression and Anxiety (NESDA), including individuals with current comorbid anxiety and depressive disorders (N = 531), only a current depression (N = 304), only a current anxiety disorder (N = 548), remitted depressive and/or anxiety disorders (N = 897), and healthy controls (N = 634). Forty metabolites from a proton nuclear magnetic resonance lipid-based metabolomics panel were analyzed. First, we examined differences in metabolites between disorder groups and healthy controls. Next, we assessed whether depression or anxiety clinical characteristics (severity and symptom duration) were associated with metabolites.

Results: As compared to healthy controls, seven metabolomic alterations were found in the group with only depression, reflecting an inflammatory (glycoprotein acetyls; Cohen's d = 0.12, p = 0.002) and atherogenic-lipoprotein-related (e.g., apolipoprotein B: Cohen's d = 0.08, p = 0.03, and VLDL cholesterol: Cohen's d = 0.08, p = 0.04) profile. The comorbid group showed an attenuated but similar pattern of deviations. No metabolomic alterations were found in the group with only anxiety disorders. The majority of metabolites associated with depression diagnosis were also associated with depression severity; no associations were found with anxiety severity or disease duration.

Conclusion: While substantial clinical overlap exists between depressive and anxiety disorders, this study suggests that altered inflammatory and atherogenic-lipoprotein-related metabolomic profiles are uniquely associated with depression rather than anxiety disorders.

Keywords: anxiety; depression; metabolomics.

FIGURE 1

Comparisons between diagnosed groups and healthy controls of metabolites that differed across groups in ANCOVA. Forest plot presents estimated regression coefficients and 95% confidence intervals adjusted for age, sex, smoking status, fasting status, years of education, number of somatic diseases, and BMI, only for metabolites that were found to be significantly different across groups in ANCOVAs. Results were obtained from linear regressions in which group comparisons between each diagnosed group of depression and anxiety disorders and healthy controls were performed. *indicates that the disorder group differed from healthy controls at p < 0.05. The superscripts next to the metabolite indicate the metabolite category, as defined by Nightingale Health Ltd. ^aInflammation, ^bFatty acids, ^cglycerides and phospholipids, ^dapolipoproteins, ^elipoprotein and particle size, ^fcholesterol, ^gglycolysis related metabolites, ^hketone bodies, ⁱ total fatty acids and saturation measures. Metabolomic markers are ordered based on p values obtained from the ANCOVAs [Colour figure can be viewed at wileyonlinelibrary.com]

FIGURE 2

Heatmap of associations between metabolites and severity measures of anxiety and depression within entire sample. The heatmap shows the standardized effect sizes from linear models with severity scores of anxiety and depression as the predicting variable and metabolite variables as the outcome, including age, sex, education level, smoking status, fasting status, number of somatic diseases, and BMI as covariates. Bold values indicate significant associations at a false discovery rate <5%. Metabolomic markers are ordered based on p values obtained from the ANCOVAs [Colour figure can be viewed at wileyonlinelibrary.com]

FIGURE 3

Heatmap of associations between metabolites and duration of symptoms of anxiety and depression within currently affected cases. The heatmap shows the standardized effect sizes obtained from linear models with duration of symptoms of anxiety and depression as the predicting variable and metabolite variables as the outcome, including age, sex, education level, smoking status, fasting status, number of somatic diseases, and BMI as covariates. Effect sizes of duration of anxious symptoms were calculated within cases with a current diagnosis of anxiety disorder (N = 1079), and effect sizes of duration of depressive symptoms were calculated within currently depressed cases (N = 835). No significant association (at a false discovery rate <0.05) was seen. Metabolomic markers are ordered based on p values obtained from the ANCOVAs [Colour figure can be viewed at wileyonlinelibrary.com]