Global DNA hypomethylation and its correlation to the betaine level in peripheral blood of patients with schizophrenia
Global DNA hypomethylation and its correlation to the betaine level in peripheral blood of patients with schizophrenia
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DOI：
10.1016/j.pnpbp.2019.109855
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发表时间：
2020-01
影响因子：
5.6
通讯作者：
Yui Murata;Tempei Ikegame;S. Koike;Takeo Saito;M. Ikeda;Tsukasa Sasaki;N. Iwata;K. Kasai;M. Bundo;K. Iwamoto
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文献类型：
--
作者：
Yui Murata;Tempei Ikegame;S. Koike;Takeo Saito;M. Ikeda;Tsukasa Sasaki;N. Iwata;K. Kasai;M. Bundo;K. Iwamoto
越来越多的证据表明，异常的表观遗传调控参与了精神分裂症（SZ）和双相情感障碍（BD）等主要精神疾病的病理生理过程。我们之前的研究表明，首发精神分裂症（FESZ）患者血浆中甲基供体甜菜碱（N，N，N-三甲基甘氨酸）的水平显著降低。在本研究中，我们发现FESZ患者（N= 24例患者和sn = 42例对照）整体DNA甲基化水平下降，并发现整体DNA甲基化水平与整体功能评估（GAF）评分呈负相关，与血浆甜菜碱水平呈正相关。值得注意的是，甜菜碱及其代谢物（N，N-二甲基甘氨酸和肌氨酸，N-甲基甘氨酸）之间的相关性在FESZ血浆中较低或消失，但在对照组中仍然很高。我们进一步检测了慢性SZ患者（N= 388）和BD患者（N= 414）以及对照组（N= 430）的整体DNA甲基化水平，证实SZ患者存在显著的低甲基化和甜菜碱水平下降。我们还发现，BD I型患者，而不是BD II型患者，表现出明显的整体低甲基化。这些结果表明，与血细胞中甜菜碱水平降低相关的整体低甲基化在SZ和BD中是共同的，并且可能反映了共同的病理生理，如精神病症状。
Accumulating evidence suggests that aberrant epigenetic regulation is involved in the pathophysiology of major psychiatric disorders such as schizophrenia (SZ) and bipolar disorder (BD). We previously showed that the plasma level of betaine (N,N,N-trimethylglycine), a methyl-group donor, was significantly decreased in patients with first episode schizophrenia (FESZ). In this study, we identified decrease of global DNA methylation level in FESZ (N= 24 patients vsN= 42 controls), and found that global DNA methylation level was inversely correlated with scores on the global assessment of functioning (GAF) scale, and positively correlated with plasma betaine level. Notably, correlations between levels of betaine and its metabolites (N,N-dimethylglycine and sarcosine,N-methylglycine) were lower or lost in FESZ plasma, but remained high in controls. We further examined global DNA methylation levels in patients with chronic SZ (N= 388) and BD (N= 414) as well as controls (N= 430), and confirmed significant hypomethylation and decreased betaine level in SZ. We also found that patients with BD type I, but not those with BD type II, showed significant global hypomethylation. These results suggest that global hypomethylation associated with decreased betaine level in blood cells is common to SZ and BD, and may reflect common pathophysiology such as psychotic symptoms.