Reduced d-serine to total serine ratio in the cerebrospinal fluid of drug naive schizophrenic patients

Abstract

Several lines of evidence suggest that d-serine, an endogenous agonist of the glycine site on the NMDA receptors, might play a role in the pathophysiology of schizophrenia. The purpose of this study was to determine whether levels of d- and l-serine or d-serine ratio ( d-serine/total serine) in cerebrospinal fluid (CSF) were altered in first episode and drug-naive schizophrenic patients. The CSF levels of d- and l-serine in 25 male first episode and drug-naive schizophrenic patients and 17 age-matched male healthy subjects were measured using a column-switching high performance liquid chromatography system. The percentage of d-serine in the total serine of patients was significantly ( z = − 2.01, p = 0.044) lower than that of controls. This study suggests that synthetic or metabolic pathways of d-serine may be abnormal in the brain of drug-naive schizophrenic patients, supporting the NMDA receptor dysfunction hypothesis of schizophrenia.