Takano Yumiko, Ozeki Yuji, Sekine Masae, Fujii Kumiko, Watanabe Takashi, Okayasu Hiroaki, Shinozaki Takahiro, Aoki Akiko, Akiyama Kazufumi, Homma Hiroshi, Shimoda Kazutaka
Department of Psychiatry, Dokkyo Medical University School of Medicine, 880 Kitakobayashi, Mibu, Tochigi Japan.
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.
Ann Gen Psychiatry. 2016 Aug 31;15(1):23. doi: 10.1186/s12991-016-0113-3. eCollection 2016.
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.
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.
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.
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.
在精神分裂症（SZ）患者中已观察到一碳代谢（OCM）的改变，但尚未对OCM进行全面研究。在OCM过程中，一个碳原子从L-丝氨酸转移至蛋氨酸，但SZ患者中L-丝氨酸与蛋氨酸之间的关系尚不清楚。我们研究了L-丝氨酸与蛋氨酸之间的关系，以全面了解SZ患者的OCM。
我们招募了45例SZ患者和30名正常对照（NC）。从所有参与者中获取全血、血浆和DNA样本。使用高效液相色谱法测量血浆L-丝氨酸、D-丝氨酸、甘氨酸、蛋氨酸和总同型半胱氨酸水平。使用化学发光蛋白结合免疫测定法测量血浆维生素B12和总叶酸。使用阳性和阴性症状量表（PANSS）评估临床症状。使用TaqMan基因分型测定系统确定参与亚甲基四氢叶酸还原酶（MTHFR）活性的MTHFR C667T基因型和A298C基因型。
方差分析用于确认SZ队列的血浆同型半胱氨酸水平高于NC组，血浆叶酸水平低于NC组。多元回归分析显示NC组中L-丝氨酸与蛋氨酸之间存在关系，而SZ组中不存在这种关系。MTHFR基因型不影响每组中L-丝氨酸与蛋氨酸之间的关系。PANSS总分与D-丝氨酸、叶酸水平及年龄显著相关。阳性PANSS评分与甘氨酸和性别均显著相关。此外，甘氨酸和D-丝氨酸均与阴性PANSS评分显著相关。
我们发现SZ患者中L-丝氨酸与蛋氨酸之间的关系受损。SZ的临床症状与OCM成分部分相关。这些发现有助于我们理解SZ患者的OCM改变，并可能解释这种改变发生的原因。
