Plasma metabolome analysis of patients with major depressive disorder

Psychiatry Clin Neurosci. 2018 May;72(5):349-361. doi: 10.1111/pcn.12638. Epub 2018 Mar 3.


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.

Keywords: biomarker; diagnosis; major depressive disorder; metabolomics; phosphoethanolamine.

MeSH terms

  • Adult
  • Biomarkers / blood*
  • Cohort Studies
  • Depressive Disorder, Major / blood*
  • Depressive Disorder, Major / physiopathology*
  • Ethanolamines / blood*
  • Female
  • Humans
  • Male
  • Metabolome / physiology*
  • Middle Aged
  • Sensitivity and Specificity


  • Biomarkers
  • Ethanolamines
  • phosphorylethanolamine