氯氮平对难治性精神分裂症患者外周血白细胞DNA甲基化的影响。
Effect of Clozapine on DNA Methylation in Peripheral Leukocytes from Patients with Treatment-Resistant Schizophrenia.
作者信息
Kinoshita Makoto, Numata Shusuke, Tajima Atsushi, Yamamori Hidenaga, Yasuda Yuka, Fujimoto Michiko, Watanabe Shinya, Umehara Hidehiro, Shimodera Shinji, Nakazawa Takanobu, Kikuchi Masataka, Nakaya Akihiro, Hashimoto Hitoshi, Imoto Issei, Hashimoto Ryota, Ohmori Tetsuro
机构信息
Department of Psychiatry, Graduate School of Biomedical Sciences, Tokushima University, 3-8-15, Kuramoto-cho, Tokushima 770-8503, Japan.
Department of Human Genetics, Graduate School of Biomedical Sciences, Tokushima University, Tokushima University Graduate School, 3-18-15, Kuramoto-cho, Tokushima 770-8503, Japan.
出版信息
Int J Mol Sci. 2017 Mar 14;18(3):632. doi: 10.3390/ijms18030632.
Clozapine is an atypical antipsychotic, that is established as the treatment of choice for treatment-resistant schizophrenia (SCZ). To date, no study investigating comprehensive DNA methylation changes in SCZ patients treated with chronic clozapine has been reported. The purpose of the present study is to reveal the effects of clozapine on DNA methylation in treatment-resistant SCZ. We conducted a genome-wide DNA methylation profiling in peripheral leukocytes (485,764 CpG dinucleotides) from treatment-resistant SCZ patients treated with clozapine (n = 21) in a longitudinal study. Significant changes in DNA methylation were observed at 29,134 sites after one year of treatment with clozapine, and these genes were enriched for "cell substrate adhesion" and "cell matrix adhesion" gene ontology (GO) terms. Furthermore, DNA methylation changes in the CREBBP (CREB binding protein) gene were significantly correlated with the clinical improvements. Our findings provide insights into the action of clozapine in treatment-resistant SCZ.
氯氮平是一种非典型抗精神病药物，已被确立为治疗难治性精神分裂症（SCZ）的首选药物。迄今为止，尚未有研究报道调查长期服用氯氮平的SCZ患者的全面DNA甲基化变化。本研究的目的是揭示氯氮平对难治性SCZ患者DNA甲基化的影响。在一项纵向研究中，我们对接受氯氮平治疗的难治性SCZ患者（n = 21）的外周血白细胞（485,764个CpG二核苷酸）进行了全基因组DNA甲基化分析。氯氮平治疗一年后，在29,134个位点观察到DNA甲基化的显著变化，这些基因在“细胞底物粘附”和“细胞基质粘附”基因本体（GO）术语中富集。此外，CREBBP（CREB结合蛋白）基因的DNA甲基化变化与临床改善显著相关。我们的研究结果为氯氮平在难治性SCZ中的作用提供了见解。
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