DNA methylation signatures of mood stabilizers and antipsychotics in bipolar disorder
DNA methylation signatures of mood stabilizers and antipsychotics in bipolar disorder
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DOI：
10.2217/epi.15.98
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发表时间：
2016-01-01
期刊：
影响因子：
3.8
通讯作者：
Boks, Marco P. M.
中科院分区：
文献类型：
--
作者：
Houtepen, Lotte C.;van Bergen, Annet H.;Boks, Marco P. M.
目的：考虑到精神药物对DNA甲基化的潜在影响，我们调查了双相情感障碍的用药是否与DNA甲基化信号有关。实验步骤：对172名双相情感障碍患者检测六种常用精神药物(锂、奎硫平、奥氮平、拉莫三平、卡马西平和丙戊酸)的血液DNA甲基化模式。在细胞类型组成调整后，我们研究了基因网络、主成分、假设驱动的基因和表观基因组范围的单个基因座。结果：在调整药物相关的细胞类型改变后，丙戊酸和奎硫平与甲基化特征的改变显著相关。结论：精神科药物对双相情感障碍患者的DNA甲基化模式的影响超过了细胞类型。因此，药物相关的DNA甲基化改变不仅是精神病学表观遗传学中的一个重要混杂因素，而且可能有助于了解药物疗效的生物学机制。
Aim: In view of the potential effects of psychiatric drugs on DNA methylation, we investigated whether medication use in bipolar disorder is associated with DNA methylation signatures. Experimental procedures: Blood-based DNA methylation patterns of six frequently used psychotropic drugs (lithium, quetiapine, olanzapine, lamotrigine, carbamazepine, and valproic acid) were examined in 172 bipolar disorder patients. After adjustment for cell type composition, we investigated gene networks, principal components, hypothesis-driven genes and epigenome-wide individual loci. Results: Valproic acid and quetiapine were significantly associated with altered methylation signatures after adjustment for drug-related changes on celltype composition. Conclusion: Psychiatric drugs influence DNA methylation patterns over and above cell type composition in bipolar disorder. Drug-related changes in DNA methylation are therefore not only an important confounder in psychiatric epigenetics but may also inform on the biological mechanisms underlying drug efficacy.