Cerebrospinal fluid D-serine concentrations in major depressive disorder negatively correlate with depression severity

J Affect Disord. 2018 Jan 15:226:155-162. doi: 10.1016/j.jad.2017.09.035. Epub 2017 Sep 27.

Abstract

Background: D-serine is an endogenous co-agonist of N-methyl-D-aspartate receptor (NMDAR) and plays an important role in glutamate neurotransmission. Several studies suggested the possible involvement of D-serine related in the pathophysiology of psychiatric disorders including major depression disorders (MDD). We tried to examine whether cerebrospinal fluid (CSF) or plasma D-serine concentrations are altered in MDD and whether D-serine concentrations correlated with disease severity.

Methods: 26 MDD patients and 27 healthy controls matched for age, sex and ethnicity were enrolled. We measured amino acids in these samples using by high-performance liquid chromatography with fluorometric detection.

Results: D-serine and L-serine, precursor of D-serine, levels in CSF or plasma were not significantly different in patients of MDD compared to controls. Furthermore, a significant correlation between D-serine levels in CSF and Hamilton Depression Rating Scale (HAMD)-17 score was observed (r = -0.65, p = 0.006). Furthermore, we found a positive correlation between CSF D-serine and HVA concentrations in MDD patients (r = 0.54, p = 0.007). CSF D-serine concentrations were correlated with those of plasma in MDD (r = 0.61, p = 0.01) but not in controls. In CSF, we also confirmed a significant correlation between D-serine and L-serine levels in MDD (r = 0.72, p < 0.0001) and controls (r = 0.70, p < 0.0001).

Conclusions: The study has some limitations; sample size was relatively small and most patients were medicated. We revealed that CSF D-serine concentrations were correlated with depression severity and HVA concentrations and further investigation were required to reveal the effect of medication and disease heterogeneity.

Keywords: D-serine; Depression; HVA; L-serine.

MeSH terms

  • Adult
  • Chromatography, High Pressure Liquid
  • Depression / physiopathology
  • Depressive Disorder, Major / cerebrospinal fluid*
  • Depressive Disorder, Major / physiopathology
  • Female
  • Humans
  • Male
  • Middle Aged
  • Psychiatric Status Rating Scales
  • Receptors, N-Methyl-D-Aspartate
  • Serine / cerebrospinal fluid*
  • Young Adult

Substances

  • Receptors, N-Methyl-D-Aspartate
  • Serine