Low D-serine levels in schizophrenia: A systematic review and meta-analysis

An increasing amount of evidence indicates that D-serine, a potent and selective endogenous coagonist of the N-methyl-D-aspartate receptor (NMDAR), is efficacious in the treatment of schizophrenia. Although the therapeutic efficacy of D-serine supplementation is based on the D-serine deficit and NMDAR hypo function hypothesis, it has not been confirmed whether D-serine levels are decreased in patients with schizophrenia compared to healthy controls. We searched the following electronic databases: Embase, Ovid Medline, and the Cochrane Library. A total of 20 studies were included in our meta-analysis. Serum D-serine levels were significantly decreased in patients with schizophrenia (standardized mean difference (SMD) = -1.008, 95% CI = -1.827 to -0.190). In the meta-regression analysis, male gender was positively correlated with serum D-serine levels (coefficient = 0.190, 95% CI = 0.070 to 0.311). D-Serine therapy combined with antipsychotics significantly improved negative (SMD = -0.319, 95% CI = -0.576 to -0.061) and positive (SMD = -0.211, 95% CI = -0.413 to -0.009) symptoms in patients with schizophrenia. Our results suggest that decreased D-serine availability may justify combining D-serine therapy with antipsychotics in patients with schizophrenia. However, clinical methodological heterogeneity across studies should be considered a major limitation of this analysis. (C) 2016 Elsevier Ireland Ltd. All rights reserved.