Plasma alanine levels increase in patients with schizophrenia as their clinical symptoms improve—Results from the Juntendo University Schizophrenia Projects (JUSP)

Since oral administration of d-alanine, an agonist that binds to the glycine site of N-methyl-d-aspartate (NMDA) receptors, improves the positive and cognitive symptoms of patients with schizophrenia, measurement of endogenous plasma alanine levels could serve as a clinical marker for schizophrenia severity and improvement. Mean plasma alanine levels were compared in healthy controls and patients with schizophrenia during the clinical course of the disease. Methods: eighty-one Japanese patients with schizophrenia and 50 age- and gender-matched healthy controls were studied. Plasma alanine levels were measured twice, during the acute stage and during the remission stage, using high-performance liquid chromatography. On admission, lower plasma alanine levels in patients with schizophrenia were accompanied by more severe schizophrenic symptoms, especially positive symptoms. The plasma alanine levels in patients with schizophrenia increased significantly from the time of admission to discharge, when they were significantly higher than control levels. An increase in plasma alanine levels from the acute stage to the remission stage of schizophrenia was correlated with improvement in symptoms. Drug-naïve patients did not show a significant difference in plasma alanine levels when compared with healthy controls. The measurement of plasma alanine levels may be a therapeutic marker for schizophrenia.