Herringa Ryan J, Roseboom Patrick H, Kalin Ned H
Neuroscience Training Program, University of Wisconsin-Madison, Madison, WI, USA.
Neuropsychopharmacology. 2006 Aug;31(8):1822-31. doi: 10.1038/sj.npp.1301038. Epub 2006 Feb 8.
Stressful life events are commonly associated with the onset and maintenance of psychopathology and much research has focused on the role of the corticotropin-releasing factor (CRF) system in mediating psychopathology. Since CRF serves to integrate the stress response, it is possible that the CRF system plays a role as a neurochemical linkage between stress and psychopathology. CRF-binding protein (CRF-BP) is thought to modulate CRF activity by decreasing its actions. Therefore, in some psychopathological states, alterations in CRF-BP function may contribute to dysregulation of the CRF system. Since the amygdala CRF system mediates stress- and anxiety-related behaviors and alterations in amygdala function are associated with psychopathology, we examined amygdala CRF-BP gene expression in post-mortem brains from subjects with major depression, bipolar disorder, and schizophrenia as well as in controls. In addition to characterizing the anatomic distribution of CRF-BP mRNA in the human amygdala and medial temporal lobe region, we found a significant decrease in CRF-BP mRNA levels in the basolateral amygdala of male bipolar and male schizophrenic subjects and the lateral amygdala of male bipolar subjects. These results raise the possibility that men with decreased amygdala CRF-BP may be more vulnerable to the effects of stress exposure on the etiology or maintenance of bipolar disorder or schizophrenia.
生活应激事件通常与精神病理学的发生和维持有关,许多研究都聚焦于促肾上腺皮质激素释放因子(CRF)系统在介导精神病理学方面的作用。由于CRF有助于整合应激反应,CRF系统有可能作为应激与精神病理学之间的一种神经化学联系发挥作用。CRF结合蛋白(CRF-BP)被认为通过降低CRF的作用来调节其活性。因此,在某些精神病理状态下,CRF-BP功能的改变可能导致CRF系统的失调。由于杏仁核CRF系统介导与应激和焦虑相关的行为,且杏仁核功能的改变与精神病理学有关,我们检测了重度抑郁症、双相情感障碍和精神分裂症患者以及对照组尸检大脑中杏仁核CRF-BP基因的表达。除了描述CRF-BP mRNA在人类杏仁核和内侧颞叶区域的解剖分布外,我们还发现男性双相情感障碍患者和男性精神分裂症患者基底外侧杏仁核以及男性双相情感障碍患者外侧杏仁核中的CRF-BP mRNA水平显著降低。这些结果提示,杏仁核CRF-BP降低的男性可能更容易受到应激暴露对双相情感障碍或精神分裂症病因或维持的影响。