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

•Cerebrospinal fluid (CSF) and plasma D-serine levels were measured.•D-serine contents were unaltered in major depression (MDD) relative to control.•CSF D-serine levels were significantly correlated with severity of MDD.•HVA levels showed a significant correlation with D-serine contents in CSF of MDD.•CSF D-serine levels might serve as biomarkers for MDD severity.

BackgroundD-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.Methods26 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.ResultsD-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).ConclusionsThe 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.