Plasma metabolome analysis of patients with major depressive disorder

Aim

This study sought to characterize the plasma metabolite profiling of patients with major depressive disorder (MDD).

Methods

Psychiatric assessments were made with the Structured Clinical Interview for DSM‐IV Axis I Disorders. In the exploratory cohort, plasma metabolite profiles of 34 MDD patients and 31 mentally healthy controls were compared using capillary electrophoresis‐mass spectrometry. Among the candidate metabolites, we focused on a metabolite showing the largest difference. The absolute concentrations were measured in two cohorts from a psychiatric primary care clinic to characterize the accuracy of the metabolite biomarker.

Results

Among 23 metabolites significantly lower in the MDD group than in healthy controls, we focused on phosphoethanolamine (PEA) as a candidate. The reduction of PEA levels in MDD was checked in independent clinical sample sets. An ion‐chromatography‐fluorescence detection method was developed to measure plasma PEA levels. In the preliminary cohort, we examined 34 MDD and 43 non‐MDD subjects. The area under the receiver–operator curve (AUC) was 0.92, with sensitivity/specificity greater than 88%, at a cut‐off of 1.46 μM. In the checking cohort, with 10 MDD and 13 non‐MDD subjects, AUC was 0.89, with sensitivity/specificity of 86% and 100%, respectively, at a cut‐off of 1.48 μM. Plasma PEA inversely correlated with MDD severity, depressed mood, loss of interest, and psychomotor retardation.

Conclusion

These results suggest that plasma PEA level could be a candidate biomarker of MDD in the clinical setting. Further studies comparing MDD and mentally healthy controls are needed to confirm the utility of PEA as a biomarker for depression.