Molecular profiles of schizophrenia in the CNS at different stages of illness.
Molecular profiles of schizophrenia in the CNS at different stages of illness.
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DOI：
10.1016/j.brainres.2008.08.023
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发表时间：
2008-11-06
期刊：
影响因子：
2.9
通讯作者：
Thomas EA
中科院分区：
文献类型：
--
作者：
Narayan S;Tang B;Head SR;Gilmartin TJ;Sutcliffe JG;Dean B;Thomas EA
临床和影像研究的结果为精神分裂症随着疾病的进展而变化提供了证据，然而，可能在疾病的不同阶段发生的潜在分子差异尚未被研究。为了验证精神分裂症的分子基础从早期到慢性病变化的假设，我们分析了不同疾病阶段的精神分裂症受试者前额叶皮质的全基因组表达模式，以及他们的年龄和性别匹配的对照组。结果表明，基因表达谱随疾病阶段的不同而变化很大，因此在短期疾病的受试者中检测到的基因表达差异最大(≤从诊断起4年)。综合途径分析显示，每个确定的疾病阶段都与不同系统和重叠系统中的功能障碍有关。短期疾病尤其与基因转录、金属离子结合、RNA加工和囊泡介导的运输中断有关。相比之下，长期疾病与炎症、刺激反应和免疫功能有关。我们通过实时荧光聚合酶链式反应分析验证了与这些不同功能相关的12个转录本的表达差异。虽然只有SAMSN1、CDC42BPB、DSC2和PTPRE四个基因在所有组中持续表达，但各个阶段的重叠系统都存在功能障碍，包括细胞信号转导、脂质代谢和蛋白质定位。我们的结果表明，精神分裂症的分子基础从早期阶段转变为慢性阶段，这为精神分裂症的性质随着疾病的进展而改变提供了证据。
Results from clinical and imaging studies provide evidence for changes in schizophrenia with disease progression, however, the underlying molecular differences that may occur at different stages of illness have not been investigated. To test the hypothesis that the molecular basis for schizophrenia changes from early to chronic illness, we profiled genome-wide expression patterns in prefrontal cortex of schizophrenic subjects at different stages of illness, along with their age- and sex-matched controls. Results show that gene expression profiles change dramatically depending on the stage of illness, whereby the greatest number and magnitude of gene expression differences were detected in subjects with short-term illness (≤ 4 years from diagnosis). Comprehensive pathways analyses revealed that each defined stage of illness was associated with dysfunction in both distinct, as well as overlapping systems. Short-term illness was particularly associated with disruptions in gene transcription, metal ion binding, RNA processing and vesicle-mediated transport. In contrast, long-term illness was associated with inflammation, stimulus-response and immune functions. We validated expression differences of 12 transcripts associated with these various functions by real-time PCR analysis. While only four genes, SAMSN1, CDC42BPB, DSC2 and PTPRE, were consistently expressed across all groups, there was dysfunction in overlapping systems among all stages, including cellular signal transduction, lipid metabolism and protein localization. Our results demonstrate that the molecular basis for schizophrenia changes from early to chronic stages, providing evidence for a changing nature of schizophrenia with disease progression.
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影响因子：
10.6
作者：
Harvey, PD;Silverman, JM;Davis, KL
通讯作者：
Davis, KL
DOI：
10.1073/pnas.96.17.9873
发表时间：
1999-08-17
影响因子：
11.1
作者：
Andrés, ME;Burger, C;Mandel, G
通讯作者：
Mandel, G
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
影响因子：
7.2
作者：
Harvey, PD;Bertisch, H;Davis, KL
通讯作者：
Davis, KL
影响因子：
10.6
作者：
Arion, Dominique;Unger, Travis;Mirnics, Karoly
通讯作者：
Mirnics, Karoly