Altered microRNA expression profiles in postmortem brain samples from individuals with schizophrenia and bipolar disorder.
Altered microRNA expression profiles in postmortem brain samples from individuals with schizophrenia and bipolar disorder.
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DOI：
10.1016/j.biopsych.2010.09.039
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发表时间：
2011-01-15
影响因子：
10.6
通讯作者：
Brzustowicz, Linda M.
中科院分区：
文献类型：
--
作者：
Moreau, Michael P.;Bruse, Shannon E.;David-Rus, Richard;Buyske, Steven;Brzustowicz, Linda M.
MicroRNA (miRNA) 是基因表达的有效调节因子，在大脑发育和功能中发挥着重要作用。我们假设患有严重精神疾病的个体中 miRNA 表达谱发生了改变。使用实时定量 PCR，我们比较了精神分裂症患者、双相情感障碍患者和精神健康对照受试者（每组 n = 35）的死后脑组织样本中 435 种 miRNA 和 18 种 snoRNA 的表达。所有受试者均可以获得详细的人口统计数据、样本选择和储存条件以及药物和物质暴露史。贝叶斯模型平均用于同时评估这些协变量以及精神病表型对 miRNA 表达谱的影响。在考虑的变量中，样本储存时间、大脑 pH 值、死亡时的酒精含量和尸检间隔被发现对 miRNA 的影响最大。 19% 的分析 miRNA 表现出由于精神分裂症或双相情感障碍的诊断而改变表达的积极证据。这两种情况都与 miRNA 表达水平降低有关，双相情感障碍的影响更为明显。这项研究表明，几种 miRNA 的适度表达不足可能与严重精神病的复杂发病机制有关。
MicroRNAs (miRNAs) are potent regulators of gene expression with proposed roles in brain development and function. We hypothesized that miRNA expression profiles are altered in individuals with severe psychiatric disorders. Using real-time quantitative PCR, we compared the expression of 435 miRNAs and 18 snoRNAs in post-mortem brain tissue samples from individuals with schizophrenia, individuals with bipolar disorder, and psychiatrically healthy control subjects (n = 35 each group). Detailed demographic data, sample selection and storage conditions, and drug and substance exposure histories were available for all subjects. Bayesian model averaging was used to simultaneously assess the impact of these covariates as well as the psychiatric phenotype on miRNA expression profiles. Of the variables considered, sample storage time, brain pH, alcohol at time of death, and post-mortem interval were found to affect the greatest proportion of miRNAs. 19% of miRNAs analyzed exhibited positive evidence of altered expression due to a diagnosis of schizophrenia or bipolar disorder. Both conditions were associated with reduced miRNA expression levels, with a much more pronounced effect observed for bipolar disorder. This study suggests that modest under-expression of several miRNAs may be involved in the complex pathogenesis of major psychosis.
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影响因子：
14.9
作者：
Chen C;Ridzon DA;Broomer AJ;Zhou Z;Lee DH;Nguyen JT;Barbisin M;Xu NL;Mahuvakar VR;Andersen MR;Lao KQ;Livak KJ;Guegler KJ
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10.5
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作者：
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作者：
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通讯作者：
Hammond SM
影响因子：
6.6
作者：
Craddock, N;O'Donovan, MC;Owen, MJ
通讯作者：
Owen, MJ