Transcriptome alterations in the prefrontal cortex of subjects with schizophrenia who committed suicide.
Transcriptome alterations in the prefrontal cortex of subjects with schizophrenia who committed suicide.
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发表时间：
2008-03
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通讯作者：
K. Garbett;Rodica Gal-Chis;G. Gaszner;D. Lewis;K. Mirnics
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作者：
K. Garbett;Rodica Gal-Chis;G. Gaszner;D. Lewis;K. Mirnics
为了更好地了解精神分裂症患者自杀相关的病理生理事件，我们对自杀的精神分裂症患者、死于非自杀原因的精神分裂症患者和匹配的对照组患者的额叶皮层进行了DNA微阵列表达谱分析。使用HU 133 A和HU 133 B Affytosis寡核苷酸阵列对> 40，000个基因进行同时表达谱分析。我们的结论是，精神分裂症的自杀与前额叶皮层中的一些基因表达变化有关，这些变化与对照组和未自杀的精神分裂症受试者中观察到的变化不同。此外，所观察到的基因表达特征包含HTR 2A 5-羟色胺受体转录物的前额叶皮质下调，加强了先前报道的遗传易感性报告。由于观察到的转录变化可能会在几天或几周内发生，这些数据表明自杀的分子易感性的发展明显早于自杀行为的发生。最后，所提供的数据也加强了精神分裂症受试者神经免疫转录组紊乱的先前报告。
To better understand the pathophysiological events associate with suicide in subjects with schizophrenia, we performed a DNA microarray expression profiling of the frontal cortex of subjects with schizophrenia who committed suicide, subjects with schizophrenia who died of non-suicidal causes and matched control subjects. Simultaneous expression profiling for >40,000 genes was performed using HU133A and HU133B Affymetrix oligonucleotide arrays. We conclude that suicide in schizophrenia is associated with a number of gene expression changes in the prefrontal cortex that are distinct from both of that observed in controls and subjects with schizophrenia who did not commit suicide. Furthermore, the observed gene expression signature contains a prefrontal cortical downregulation of the HTR2A serotonin receptor transcript, strengthening previously reported genetic susceptibility reports. As the observed transcript changes are likely developing over days or weeks, these data argue that the molecular predisposition to suicide develops significantly earlier than the act of suicide occurs. Finally, the presented data also strengthens previous reports of neuroimmune transcriptome disturbances in subjects with schizophrenia.