NMDA-receptor coagonists in serum, plasma, and cerebrospinal fluid of schizophrenia patients: A meta-analysis of case-control studies

Serine and other amino acids that function as coagonists at the N-methyl-d-aspartate receptor (NMDAR) have been extensively investigated in schizophrenia (SCZ). However, studies comparing amino acid levels in body fluids of SCZ patients with healthy controls have yielded inconsistent results. We therefore conducted a meta-analysis (search: May 9, 2013) of serine, l-serine, d-serine, glycine, alanine, proline, and aspartate levels in blood and cerebrospinal fluid (CSF) obtained from adult SCZ patients and healthy controls. Standardized differences of means (SDMs) were computed, and heterogeneity, subgroup, sensitivity, and publication bias analyses were conducted. Blood serine levels were found to be significantly higher in SCZ patients compared to healthy controls (SDM = 0.280 (0.021-0.540), p = 0.034; N = 1671 subjects), whereas CSF serine, l-serine, d-serine, glycine, alanine, proline, and aspartate levels did not differ. Stratification by sex suggested that the case-control difference in blood serine levels particularly applies to male subjects. These results provide support for blood serine level aberrations in SCZ patients and warrant further research to disentangle the involvement of serine with SCZ in both sexes.