Gene expression alterations in bipolar disorder postmortem brains.

Bipolar disorder (BD) is a mental illness of unknown neuropathology and has several genetic associations. Antipsychotics are effective for the treatment of acute mania, psychosis, or mixed states in BD individuals. We aimed to identify gene transcripts differentially expressed in postmortem brains from BD individuals in both the antipsychotics-exposed (exposed) and non-exposed groups and controls. We quantified the abundance of gene transcripts in postmortem brains (brains) of seven exposed, seven non-exposed, and 12 controls with the Affymetrix U133P2 GeneChip microarrays and technologies. We applied a q-value of ≤ 0.005 to identify statistically significant transcripts with mean abundance differences between non-exposed and controls (and/or exposed). We identified 2,191 unique genes with significantly altered expression levels in non-exposed brains compared to those in the control and exposed groups. The expression levels of these genes were not significantly different between exposed and controls, suggesting a normalization effect of antipsychotics on the expression of these genes. Gene Ontology (GO) enrichment analysis showed significant (Bonferroni p ≤ 0.05) clustering of subgroups of the 2,191 genes under a broad number of GO terms, noticeably the protein products of genes enriched are critical to the function of synapses, including intracellular protein trafficking, synaptic vesicle biogenesis, transport, releasing and recycling, as well as organization and stabilization of the node of Ranvier. These results support a hypothesis of synaptic and intercellular communication impairment in BD. The apparent normalization of expression patterns with exposure to antipsychotic medication may represent a physiological process that relates both to etiology and improvement patterns of the disorder.

双相情感障碍（BD）是一种神经病理学不明的精神疾病，有多种基因关联。抗精神病药物对治疗双相情感障碍患者的急性躁狂、精神病性症状或混合状态有效。我们旨在确定在使用抗精神病药物（暴露组）和未使用抗精神病药物（非暴露组）的双相情感障碍患者以及对照组的尸检大脑中差异表达的基因转录本。 我们使用Affymetrix U133P2基因芯片和相关技术对7例暴露组、7例非暴露组和12例对照组的尸检大脑中的基因转录本丰度进行了定量。我们应用q值≤0.005来确定在非暴露组与对照组（和/或暴露组）之间平均丰度有差异的具有统计学意义的转录本。 我们确定了2191个独特的基因，与对照组和暴露组相比，这些基因在非暴露组大脑中的表达水平有显著改变。这些基因在暴露组和对照组之间的表达水平没有显著差异，这表明抗精神病药物对这些基因的表达有正常化作用。基因本体论（GO）富集分析显示，在大量的GO术语下，2191个基因的亚组有显著（Bonferroni校正p≤0.05）的聚类，值得注意的是，富集基因的蛋白质产物对突触功能至关重要，包括细胞内蛋白质运输、突触小泡的生物发生、运输、释放和再循环，以及郎飞结的组织和稳定。 这些结果支持双相情感障碍中突触和细胞间通讯受损的假说。使用抗精神病药物后表达模式的明显正常化可能代表一种与该疾病的病因和改善模式相关的生理过程。