title: Phosphoserine phosphatase activity is elevated and correlates negatively with plasma d-serine concentration in patients with schizophrenia.
abstract: The pathophysiology of schizophrenia may involve N-methyl-D-aspartate receptor (NMDAR) hypofunction. D-3serine and glycine are endogenous l-serine-derived NMDAR co-agonists. We hypothesized that the l-serine synthesis pathway could be involved in schizophrenia. We measured the activity of phosphoserine phosphatase (PSP), a rate-limiting enzyme in l-serine synthesis, in peripheral blood mononuclear cells of 54 patients with schizophrenia and 49 normal control subjects. Plasma amino acid (l-serine, d-serine, glycine, glutamine, and glutamate) levels were measured by high performance liquid chromatography. Peripheral blood mRNA expression levels of PHGDH, PSAT1, PSP, and SR, determined by quantitative real-time PCR were compared between patients and controls. PSP activity was higher in patients than in controls, especially in male patients. In male patients, the plasma l-serine concentration was higher than that in controls. In patients, PSP activity was negatively correlated with plasma d-serine and glycine levels. Furthermore, PSP activity was positively correlated with plasma l-serine concentration. These results were statistically significant only in male patients. PSP, PSAT1, and PHGDH mRNA levels were lower in patients than in controls, except when the PHGDH expression level was compared with ACTB expression. In summary, we found the l-serine synthesis system to be altered in patients with schizophrenia, especially in male patients.
authors.affiliation: Department of Psychiatry, Dokkyo Medical University School of Medicine, Mibu, Tochigi, Japan; Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan. Electronic address: ozeki@dokkyomed.ac.jp.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Ozeki
authors.affiliation: Laboratory of Biomolecular Science, Graduate School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan.
authors.forename: Masae
authors.initials: M
authors.lastname: Sekine
authors.affiliation: Department of Psychiatry, Dokkyo Medical University School of Medicine, Mibu, Tochigi, Japan.
authors.forename: Kumiko
authors.initials: K
authors.lastname: Fujii
authors.affiliation: Department of Psychiatry, Dokkyo Medical University School of Medicine, Mibu, Tochigi, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Watanabe
authors.affiliation: Department of Psychiatry, Dokkyo Medical University School of Medicine, Mibu, Tochigi, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Okayasu
authors.affiliation: Department of Psychiatry, Dokkyo Medical University School of Medicine, Mibu, Tochigi, Japan.
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Takano
authors.affiliation: Department of Psychiatry, Dokkyo Medical University School of Medicine, Mibu, Tochigi, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Shinozaki
authors.affiliation: Department of Psychiatry, Dokkyo Medical University School of Medicine, Mibu, Tochigi, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Aoki
authors.affiliation: Department of Biological Psychiatry and Neuroscience, Dokkyo Medical University School of Medicine, Mibu, Tochigi, Japan.
authors.forename: Kazufumi
authors.initials: K
authors.lastname: Akiyama
authors.affiliation: Laboratory of Biomolecular Science, Graduate School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Homma
authors.affiliation: Department of Psychiatry, Dokkyo Medical University School of Medicine, Mibu, Tochigi, Japan.
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Shimoda
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010744:Phosphoric Monoester Hydrolases / Q000097:blood*; D012559:Schizophrenia / Q000097:blood* / Q000188:drug therapy; D012694:Serine / Q000097:blood*
chemical_list: D014150:Antipsychotic Agents; D012694:Serine; D010744:Phosphoric Monoester Hydrolases; C022394:phosphoserine phosphatase
keywords: N-methyl-D-aspartate receptor (NMDAR) hypofunction hypothesis; PHGDH; PSAT1; PSP; l-serine synthesis