Department of Genetics, Rutgers University, Piscataway, New Jersey 08854-8095, USA.
Biol Psychiatry. 2011 Jan 15;69(2):188-93. doi: 10.1016/j.biopsych.2010.09.039.
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.
With real-time quantitative polymerase chain reaction, we compared the expression of 435 miRNAs and 18 small nucleolar RNAs in postmortem 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 postmortem interval were found to affect the greatest proportion of miRNAs. Of miRNAs analyzed, 19% 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 underexpression of several miRNAs might be involved in the complex pathogenesis of major psychosis.
MicroRNAs (miRNAs) 是基因表达的有效调控因子，其在脑发育和功能中的作用已被提出。我们假设在患有严重精神疾病的个体中，miRNA 表达谱发生改变。
采用实时定量聚合酶链反应，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者（每组 35 人）死后脑组织样本中 435 种 miRNAs 和 18 种小核仁 RNA 的表达。所有受试者均有详细的人口统计学数据、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表型对 miRNA 表达谱的影响。
在所考虑的变量中，发现样本储存时间、脑 pH 值、死亡时的酒精含量和死后间隔时间对 miRNA 的影响最大。在分析的 miRNAs 中，由于诊断为精神分裂症或双相情感障碍，有 19%表现出表达改变的阳性证据。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 miRNAs 的适度低表达可能与主要精神病的复杂发病机制有关。
