Molecular phenotypes associated with antipsychotic drugs in the human caudate nucleus.
Molecular phenotypes associated with antipsychotic drugs in the human caudate nucleus.
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DOI：
10.1038/s41380-022-01453-6
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发表时间：
2022-04
影响因子：
11
通讯作者：
Weinberger, Daniel R.
中科院分区：
文献类型：
--
作者：
Mandell, Kira A. Perzel;Eagles, Nicholas J.;Deep-Soboslay, Amy;Tao, Ran;Han, Shizhong;Wilton, Richard;Szalay, Alexander S.;Hyde, Thomas M.;Kleinman, Joel E.;Jaffe, Andrew E.;Weinberger, Daniel R.
抗精神病药物是目前治疗精神分裂症和其他精神病的一线药物。然而，由于组织进入困难以及与疾病状态相关的混杂因素，它们对人脑的分子影响研究很少。在这里，我们研究了与人类尾状核中抗精神病药物毒理学阳性状态相关的基因表达和 DNA 甲基化的差异。我们发现 DNA 甲基化在全基因组范围内没有显着差异，但基因表达存在丰富差异。这些基因表达差异总体上与精神分裂症病例和对照之间的基因表达差异非常相似。有趣的是，基于抗精神病药物毒理学的基因表达差异在大脑区域之间是不同的，这可能是由于受影响的细胞类型差异所致。我们最终评估了与小鼠模型中效果的相似性，发现了一些重叠的效果，但也存在许多差异。首次观察抗精神病药物在人脑中的分子效应时，我们发现缺乏表观遗传效应是出乎意料的，这可能是因为长期治疗效果可能在较长时间内相对稳定。
Antipsychotic drugs are the current first-line of treatment for schizophrenia and other psychotic conditions. However, their molecular effects on the human brain are poorly studied, due to difficulty of tissue access and confounders associated with disease status. Here we examine differences in gene expression and DNA methylation associated with positive antipsychotic drug toxicology status in the human caudate nucleus. We find no genome-wide significant differences in DNA methylation, but abundant differences in gene expression. These gene expression differences are overall quite similar to gene expression differences between schizophrenia cases and controls. Interestingly, gene expression differences based on antipsychotic toxicology are different between brain regions, potentially due to affected cell type differences. We finally assess similarities with effects in a mouse model, which finds some overlapping effects but many differences as well. As a first look at the molecular effects of antipsychotics in the human brain, the lack of epigenetic effects is unexpected, possibly because long term treatment effects may be relatively stable for extended periods.
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影响因子：
3
作者：
Eagles NJ;Burke EE;Leonard J;Barry BK;Stolz JM;Huuki L;Phan BN;Serrato VL;Gutiérrez-Millán E;Aguilar-Ordoñez I;Jaffe AE;Collado-Torres L
通讯作者：
Collado-Torres L
影响因子：
16.2
作者：
Collado-Torres, Leonardo;Burke, Emily E.;Narurkar, Rujuta
通讯作者：
Narurkar, Rujuta
影响因子：
81.5
作者：
Kahn, Rene S.;Sommer, Iris E.;Insel, Thomas R.
通讯作者：
Insel, Thomas R.
影响因子：
10.6
作者：
Konopaske, Glenn T.;Dorph-Petersen, Karl-Anton;Lewis, David A.
通讯作者：
Lewis, David A.
影响因子：
7.6
作者：
HALL, H;SEDVALL, G;FARDE, L
通讯作者：
FARDE, L