title: Decreased serum levels of D-serine in patients with schizophrenia: evidence in support of the N-methyl-D-aspartate receptor hypofunction hypothesis of schizophrenia.
abstract: 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.
authors.affiliation: Department of Psychiatry, Graduate School of Medicine, Chiba University, Japan. hashimoto@faculty.chiba-u.jp
authors.forename: Kenji
authors.initials: K
authors.lastname: Hashimoto
authors.forename: Takeshi
authors.initials: T
authors.lastname: Fukushima
authors.forename: Eiji
authors.initials: E
authors.lastname: Shimizu
authors.forename: Naoya
authors.initials: N
authors.lastname: Komatsu
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Watanabe
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Shinoda
authors.forename: Michiko
authors.initials: M
authors.lastname: Nakazato
authors.forename: Chikara
authors.initials: C
authors.lastname: Kumakiri
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Okada
authors.forename: Hisanori
authors.initials: H
authors.lastname: Hasegawa
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Imai
authors.forename: Masaomi
authors.initials: M
authors.lastname: Iyo
mesh_terms: 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
chemical_list: D015415:Biomarkers; D005998:Glycine; D019998:Racemases and Epimerases; D016194:Receptors, N-Methyl-D-Aspartate; D012694:Serine; D000099300:Serine Racemase