Correlation analysis between genome-wide expression profiles and cytoarchitectural abnormalities in the prefrontal cortex of psychiatric disorders
Correlation analysis between genome-wide expression profiles and cytoarchitectural abnormalities in the prefrontal cortex of psychiatric disorders
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DOI：
10.1038/mp.2008.99
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发表时间：
2010-03-01
影响因子：
11
通讯作者：
Webster, M. J.
中科院分区：
文献类型：
--
作者：
Kim, S.;Webster, M. J.
在精神分裂症、双相情感障碍和抑郁症患者的前额叶皮层中，已经描述了细胞结构异常。然而，很少有人知道与这些异常相关的基因表达谱。全基因组表达谱分析技术提供了一种无偏倚的方法来鉴定候选基因和可能与复杂生物学性状（如细胞结构）相关的生物学过程。在这项研究中，我们通过使用来自54名受试者（精神分裂症，n = 14;双相情感障碍，n = 13;抑郁症，n = 12和对照组n = 15）的额叶皮层死后样本的公开可用的微阵列元数据和细胞结构数据来探索与异常相关的表达谱。全基因组表达水平和细胞结构特征之间的相关性分析显示，818个基因与所有受试者神经元周少突胶质细胞数量的减少显著相关。在所有受试者中，共有600个基因与钙结合蛋白阳性中间神经元密度的降低显著相关。多个生物过程，包括细胞代谢，中枢神经系统的发展，细胞运动和程序性细胞死亡显着过度的相关基因列表。这些研究结果可能提供新的见解的分子机制，神经少突胶质细胞和钙结合蛋白的GABA能中间神经元的前额叶皮层的主要精神疾病的细胞结构异常的基础。Molecular Psychiatry（2010）15，326-336; doi：10.1038/mp.2008.99; 2008年9月2日在线发表
Cytoarchitectural abnormalities have been described in the prefrontal cortex of subjects with schizophrenia, bipolar disorder and depression. However, little is known about the gene expression profiles associated with these abnormalities. Genome-wide expression profiling technology provides an unbiased approach to identifying candidate genes and biological processes that may be associated with complex biological traits such as cytoarchitecture. In this study, we explored expression profiles associated with the abnormalities by using publicly available microarray metadata and cytoarchitectural data from post-mortem samples of the frontal cortex from 54 subjects (schizophrenia, n = 14; bipolar disorder, n = 13; depression, n = 12 and controls n = 15). Correlation analysis between genome-wide expression levels and cytoarchitectural traits revealed that 818 genes were significantly correlated with a decrease in the number of perineuronal oligodendrocytes across all subjects. A total of 600 genes were significantly correlated with a decrease in density of calbindin-positive interneurons across all subjects. Multiple biological processes including cellular metabolism, central nervous system development, cell motility and programmed cell death were significantly overrepresented in both correlated gene lists. These findings may provide novel insights into the molecular mechanisms that underlie the cytoarchitectural abnormalities of perineuronal oligodendrocytes and calbindin-containing GABAergic interneurons in the prefrontal cortex of the major psychiatric disorders. Molecular Psychiatry ( 2010) 15, 326-336; doi: 10.1038/mp.2008.99; published online 2 September 2008