title: Multi-regression analysis revealed a relationship between l-serine and methionine, a component of one-carbon metabolism, in the normal control but not in the schizophrenia.
abstract: BACKGROUND
  Alterations in one-carbon metabolism (OCM) have been observed in patients with schizophrenia (SZ), but a comprehensive study of OCM has not yet been conducted. A carbon atom is transferred from l-serine to methionine during OCM, but the relationship between l-serine and methionine in SZ is not yet known. We investigated the relationship between l-serine and methionine to obtain a comprehensive understanding of OCM in SZ.
  
  
  METHODS
  We recruited forty-five patients with SZ and thirty normal controls (NC). Whole blood, plasma, and DNA specimens were obtained from all participants. Plasma l-serine, d-serine, glycine, methionine, and total homocysteine levels were measured using high-performance liquid chromatography. Plasma vitamin B12 and total folate were measured using a chemiluminescent protein-binding immunoassay. Clinical symptoms were estimated using the positive and negative syndrome scale (PANSS). The methylenetetrahydrofolate reductase (MTHFR) C667T genotype and A298C genotype, which are involved in MTHFR activity, were determined using the TaqMan genotyping assay system.
  
  
  RESULTS
  Analysis of variance was used to confirm that the SZ cohort has higher plasma homocysteine levels and lower plasma folate levels than the NC group. Multi-regression analysis revealed a relationship between l-serine and methionine in the NC group but not in the SZ group. The MTHFR genotype did not affect the relationship between l-serine and methionine in each group. The total PANSS score was significantly related to d-serine and folate levels and to age. Positive PANSS scores were significantly related to both glycine and sex. In addition, both glycine and d-serine were significantly correlated with negative PANSS scores.
  
  
  CONCLUSIONS
  We found impairment of the relationship between l-serine and methionine in SZ. Clinical symptoms of SZ were partially correlated with the OCM components. These findings contributed to our understanding of OCM alteration in SZ and may explain why the alteration occurs.
authors: Department of Psychiatry, Dokkyo Medical University School of Medicine, 880 Kitakobayashi, Mibu, Tochigi Japan.
authors: Yumiko
authors: Y
authors: Takano
authors: Department of Psychiatry, Dokkyo Medical University School of Medicine, 880 Kitakobayashi, Mibu, Tochigi Japan ; Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.
authors: Yuji
authors: Y
authors: Ozeki
authors: Laboratory of Biomolecular Science, Graduate School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan.
authors: Masae
authors: M
authors: Sekine
authors: Department of Psychiatry, Dokkyo Medical University School of Medicine, 880 Kitakobayashi, Mibu, Tochigi Japan.
authors: Kumiko
authors: K
authors: Fujii
authors: Department of Psychiatry, Dokkyo Medical University School of Medicine, 880 Kitakobayashi, Mibu, Tochigi Japan.
authors: Takashi
authors: T
authors: Watanabe
authors: Department of Psychiatry, Dokkyo Medical University School of Medicine, 880 Kitakobayashi, Mibu, Tochigi Japan.
authors: Hiroaki
authors: H
authors: Okayasu
authors: Department of Psychiatry, Dokkyo Medical University School of Medicine, 880 Kitakobayashi, Mibu, Tochigi Japan.
authors: Takahiro
authors: T
authors: Shinozaki
authors: Department of Psychiatry, Dokkyo Medical University School of Medicine, 880 Kitakobayashi, Mibu, Tochigi Japan.
authors: Akiko
authors: A
authors: Aoki
authors: Department of Biological Psychiatry and Neuroscience, Dokkyo Medical University School of Medicine, Mibu, Tochigi Japan.
authors: Kazufumi
authors: K
authors: Akiyama
authors: Laboratory of Biomolecular Science, Graduate School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan.
authors: Hiroshi
authors: H
authors: Homma
authors: Department of Psychiatry, Dokkyo Medical University School of Medicine, 880 Kitakobayashi, Mibu, Tochigi Japan.
authors: Kazutaka
authors: K
authors: Shimoda
keywords: Folate; Homocysteine; Methionine; One-carbon metabolism (OCM); Schizophrenia; l-serine