Decreased serum levels of D-serine in patients with schizophrenia: evidence in support of the N-methyl-D-aspartate receptor hypofunction hypothesis of schizophrenia.
BACKGROUND
The hypofunction of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptors has been implicated in the pathophysiology of schizophrenia. Several lines of evidence suggest that D-serine may function as an endogenous agonist of the glycine site of the NMDA receptor. The aim of this study was to examine whether serum levels of D- and L-serine in patients with schizophrenia are different from those of healthy controls.


METHODS
Forty-two patients with schizophrenia and 42 age- and sex-matched healthy controls were enrolled in this study. Symptoms were assessed using the Brief Psychiatric Rating Scale. Serum levels of total serine and D- and L-serine were measured by high-performance liquid chromatography.


RESULTS
Serum levels of D-serine in the patients with schizophrenia were significantly (z = -3.30, P =.001) lower than those of healthy controls. In contrast, serum levels of total (D and L) serine (z = -2.40, P =.02) and L-serine (z = -2.49, P =.01) in the schizophrenic patients were significantly higher than those of controls. In addition, the percentage of D-serine in the total serine in the schizophrenic patients was significantly (z = -4.78, P<.001) lower than that of controls, suggesting that the activity of serine racemase, an enzyme catalyzing the formation of D-serine from L-serine, may have been reduced in the schizophrenic patients.


CONCLUSIONS
Reduced levels of D-serine may play a role in the pathophysiology of schizophrenia, and serum D- and L-serine levels might provide a measurable biological marker for schizophrenia.
Hashimoto
Kenji
K
Department of Psychiatry, Graduate School of Medicine, Chiba University, Japan. hashimoto@faculty.chiba-u.jp
Fukushima
Takeshi
T
Shimizu
Eiji
E
Komatsu
Naoya
N
Watanabe
Hiroyuki
H
Shinoda
Naoyuki
N
Nakazato
Michiko
M
Kumakiri
Chikara
C
Okada
Shin-ichi
S
Hasegawa
Hisanori
H
Imai
Kazuhiro
K
Iyo
Masaomi
M
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D015415:Biomarkers / Q000097:blood; D010054:Brief Psychiatric Rating Scale; D002851:Chromatography, High Pressure Liquid; D005260:Female; D005998:Glycine / Q000037:antagonists & inhibitors; D006801:Humans; D008297:Male; D008875:Middle Aged; D019998:Racemases and Epimerases / Q000097:blood / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D012559:Schizophrenia / Q000097:blood* / Q000175:diagnosis / Q000503:physiopathology*; D012694:Serine / Q000097:blood* / Q000737:chemistry* / Q000378:metabolism; D012737:Sex Factors; D013237:Stereoisomerism; D000099300:Serine Racemase
D015415:Biomarkers; D005998:Glycine; D019998:Racemases and Epimerases; D016194:Receptors, N-Methyl-D-Aspartate; D012694:Serine; D000099300:Serine Racemase