Schizophrenia is a typical N-methyl-d-aspartate receptor (NMDA-R) hypofunction
disorder. Decreased d-serine (d-Ser) levels in the periphery occur in schizophrenia and may
reflect decreased availability of d-Ser to activate NMDA-R in the brain.
Objective: The objective of this study was to investigate the role of d-Ser metabolism in the
pathogenesis of schizophrenia via biochemical assays and correlates, the serum level of d-Ser,
d-serine racemase (SR) (responsible for its formation from l-serine [l-Ser]) and d-amino acid
oxidase (DAAO) (responsible for its catabolism), among different clinical types of schizophrenia
patients.
Patients and methods: This cross-sectional case–control study was carried out on 100 patients
and 50 controls. They were recruited from the outpatients’ psychiatric unit of the Neuropsychiatric
Department of Assiut University Hospital, Upper Egypt. The type of schizophrenia
was determined according to the Diagnostic and Statistical Manual of Mental Disorders,
Fourth Edition (DSM-IV), while the severity of schizophrenia was determined according to the
Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). Serum d-Ser
levels were estimated using high-performance liquid chromatography (HPLC), while serum
SR and DAAO were measured using commercially available enzyme-linked immunosorbent
assay kits.
Results: There were significantly lower mean serum levels of d-Ser and SR and significantly
higher mean serum levels of DAAO (P-value ,0.01 for each) among schizophrenia patients
when compared with the control group. Paranoid schizophrenia had the highest frequency,
with a significantly lower serum levels of d-Ser and SR in the residual type and significantly
higher serum levels of DAAO in undifferentiated and catatonic types. Combined receiveroperating
characteristic curve for serum d-Ser, SR and DAAO indicated that the best serum
level cutoff points at which schizophrenia manifestations started to appear were 61.4 mg/L
for d-Ser, 15.5 pg/mL for SR and .35.6 pg/mL for DAAO.
Conclusion: The present study confirms that disturbed d-Ser metabolism could be implicated
in the pathogenesis of schizophrenia.