Corticotropin releasing hormone in the pathophysiology of melancholic and atypical depression and in the mechanism of action of antidepressant drugs
Corticotropin releasing hormone in the pathophysiology of melancholic and atypical depression and in the mechanism of action of antidepressant drugs
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DOI：
10.1111/j.1749-6632.1995.tb44723.x
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发表时间：
1995-01-01
期刊：
影响因子：
2.3
通讯作者：
Chrousos, GP
中科院分区：
文献类型：
--
作者：
Gold, PW;Licinio, J;Chrousos, GP
抑郁症中皮质醇增多似乎优先反映下丘脑CRH分泌的激活。虽然它已被假定，这种皮质醇增多症是一种附带现象的疼痛和压力的抑郁症，我们的数据显示优先参与AVP皮质醇增多症的慢性炎症性疾病表明特异性的病理生理学皮质醇增多症抑郁症。我们的研究结果表明，丙咪嗪导致下调HPA轴在实验动物和健康对照组支持CRH的内在作用，在病理生理学的精神病药物的作用机制。我们的数据表明，皮质醇增多症不是抑郁症HPA失调的唯一形式。在一系列研究中，从库欣病患者开始，扩展到超免疫疲劳状态，如慢性疲劳综合征和非典型抑郁症的例子，如季节性情感障碍，我们有先进的数据表明下丘脑CRH神经元功能减退。这些数据提出了一个问题，即与非典型抑郁症综合征相关的摄食过多、睡眠过度和疲劳可能反映了一种有效的产生觉醒的促兴奋神经肽的中枢缺乏。根据本次研讨会其他地方提出的关于功能减退的下丘脑CRH神经元在炎症性疾病易感性中的作用的数据，这些数据也提出了与炎症表现和非典型抑郁症状相关的综合征的共同病理生理机制的问题。在这些疾病中下丘脑CRH神经元功能减退的概念也提出了在炎症性疾病和非典型抑郁综合征中神经药理学干预的新形式的问题。
Hypercortisolism in depression seems to preferentially reflect activation of hypothalamic CRH secretion. Although it has been postulated that this hypercortisolism is an epiphenomenon of the pain and stress of major depression, our data showing preferential participation of AVP in the hypercortisolism of chronic inflammatory disease suggest specificity for the pathophysiology of hypercortisolism in depression. Our findings that imipramine causes a down-regulation of the HPA axis in experimental animals and healthy controls support an intrinsic role for CRH in the pathophysiology of melancholia and in the mechanism of action of psychotropic agents. Our data suggest that hypercortisolism is not the only form of HPA dysregulation in major depression. In a series of studies, commencing in patients with Cushing's disease, and extending to hyperimmune fatigue states such as chronic fatigue syndrome and examples of atypical depression such as seasonal affective disorder, we have advanced data suggesting hypofunction of hypothalamic CRH neurons. These data raise the question that the hyperphagia, hypersomnia, and fatigue associated with syndromes of atypical depression could reflect a central deficiency of a potent arousal-producing anorexogenic neuropeptide. In the light of data presented elsewhere in this symposium regarding the role of a hypofunctioning hypothalamic CRH neuron in susceptibility to inflammatory disease, these data also raise the question of a common pathophysiological mechanism in syndromes associated both with inflammatory manifestations and atypical depressive symptoms. This concept of hypofunctioning of hypothalamic CRH neurons in these disorders also raises the question of novel forms of neuropharmacological intervention in both inflammatory diseases and atypical depressive syndromes.