Changes in plasma glycine, L-serine, and D-serine levels in patients with schizophrenia as their clinical symptoms improve: results from the Juntendo University Schizophrenia Projects (JUSP)

Objectives

Based on the hypothesis of NMDA receptor hypofunction in schizophrenia, plasma glycine, l-serine, and d-serine levels have been studied, since they could serve as biological markers. However, changes over time in the levels of these amino acids in schizophrenic patients have not been investigated. To clarify the mean plasma glycine, l-serine, and d-serine levels in patients with schizophrenia, levels of these amino acids were compared between healthy controls and patients with schizophrenia. The plasma levels of these amino acids during the clinical course of schizophrenia were also compared.

Methods

Eighty-nine Japanese patients with schizophrenia and 50 age- and gender-matched healthy controls were studied. Plasma glycine, l-serine, and d-serine levels and their ratios were measured twice, during the acute stage and during the remission stage, using high-performance liquid chromatography.

Results

The admission plasma glycine, l-serine, and d-serine levels of schizophrenic patients were higher than those of healthy controls. There were no significant differences between drug-naïve patients and healthy controls in the admission levels of the plasma amino acids, but chronically medicated patients had higher admission plasma glycine and d-serine levels. Only the d-serine level and the d-/l-serine ratio were markedly significantly increased in schizophrenic patients from the time of admission to the time of discharge as their clinical symptoms improved. In addition, the increase in the plasma d-serine levels of drug-naïve patients was correlated with improvements in positive symptoms.

Conclusions

Plasma amino acid levels, especially d-serine levels, could be useful as a “therapeutic” or “clinical state” marker in patients with acute schizophrenia.