One-carbon and energy metabolism in major depression compared to chronic depression in adolescent outpatients: A metabolomic pilot study

Abstract

While considered less severe than major depressive disorder (MDD), chronic depression has a devastating effect on people's lives. Metabolic alterations related to chronicity are still widely unknown. We investigated metabolic alterations in patients with depression and compared the episodic and chronic forms. The study participants comprised 76 adolescent outpatients (33 MDD, 43 chronic depression). Patients’ serum samples were analyzed with targeted metabolite analysis, yielding results for 102 metabolites associated, for example, with amino acid, energy, lipid, and one-carbon metabolism. After controlling for background factors, the chronic depression group had higher levels of choline (Cohen's d = 0.52 and unadjusted 95% confidence interval [0.05, 0.98]), glutamine (d = 0.42 [-0.04, 0.88]), glycine (d = 0.41 [-0.04, 0.87]), glycine betaine (d = 0.48 [0.02, 0.94]), guanidinoacetic acid (d = 0.23 [-0.23, 0.68]), octanoylcarnitine (d = 0.60 [0.13, 1.06]), phosphoethanolamine (d = 0.34 [-0.12, 0.79]) and succinate (d = 0.61 [0.14, 1.07]), and lower levels of glutamate (d = -0.66 [-1.12, -0.18]) when compared to the MDD group, although these differences did not remain after correction for multiple testing. The sample size was small for targeted metabolomic analysis, and the study did not include a healthy control group. These preliminary results indicate putative differences in one-carbon metabolism and energy metabolism between chronic depression and MDD, possibly due to long-term chronic stress. Metabolic profiles appear to have the potential firstly to identify and distinguish different types of depression, and secondly to help in personalizing treatments in the future.