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).
OBJECTIVE
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.
Ohnuma
Tohru
T
Juntendo University Schizophrenia Projects (JUSP), Department of Psychiatry, Juntendo University, School of Medicine, 2-1-1 Hongo Bunkyo-ku, Tokyo 113-8421, Japan. tohru.oonuma@nifty.ne.jp
Sakai
Yoshie
Y
Maeshima
Hitoshi
H
Hatano
Tokiko
T
Hanzawa
Ryo
R
Abe
Sawako
S
Kida
Sayaka
S
Shibata
Nobuto
N
Suzuki
Toshihito
T
Arai
Heii
H
D000293:Adolescent; D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D005260:Female; D005998:Glycine / Q000097:blood*; D006785:Hospitals, University; D006801:Humans; D008297:Male; D008875:Middle Aged; D012559:Schizophrenia / Q000097:blood* / Q000188:drug therapy; D012694:Serine / Q000097:blood*; D013997:Time Factors; D055815:Young Adult
D014150:Antipsychotic Agents; D012694:Serine; D005998:Glycine