Neurosteroid, GABAergic and hypothalamic pituitary adrenal (HPA) axis regulation: what is the current state of knowledge in humans?
Neurosteroid, GABAergic and hypothalamic pituitary adrenal (HPA) axis regulation: what is the current state of knowledge in humans?
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DOI：
10.1007/s00213-014-3572-8
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发表时间：
2014-09
影响因子：
3.4
通讯作者：
Girdler, Susan S.
中科院分区：
文献类型：
--
作者：
Crowley, Shannon K.;Girdler, Susan S.
关键词：
大量流行病学文献表明，慢性压力与情感障碍的发展之间存在关联。然而，这种关系的确切生物学基础仍然难以捉摸。下丘脑垂体肾上腺 (HPA) 轴的激活和抑制是人类对压力的反应和适应的核心，涉及多层次、多系统的神经生物应激反应，这种反应既复杂又不稳定。这个复杂系统的失调会对人类压力相关疾病产生影响。 Robert Purdy 及其同事的开创性研究为加深我们对应激源类固醇激素及其神经活性代谢物（称为神经类固醇）对 HPA 轴调节的理解奠定了基础，这些代谢物是中枢神经系统中 GABAA 受体功能的有效变构调节剂。这篇综述将描述关于神经类固醇对 HPA 轴响应急性和慢性应激的调节的已知信息，特别是我们对人类这一过程的了解的现状。这项研究对人类压力相关疾病发展的影响是在两种与人类压力相关的精神疾病——重度抑郁症和经前焦虑症——的背景下讨论的。神经类固醇介导的 HPA 轴失调是一种潜在的病理生理机制，可能跨越传统的精神病学诊断分类。确定了未来的研究方向。
A robust epidemiological literature suggests an association between chronic stress and the development of affective disorders. However, the precise biological underpinnings of this relationship remain elusive. Central to the human response and adaptation to stress, activation and inhibition of the hypothalamic pituitary adrenal (HPA) axis involves a multi-level, multi-system, neurobiological stress response which is as comprehensive in its complexity as it is precarious. Dysregulation in this complex system has implications for human stress related illness. The pioneering research of Robert Purdy and colleagues has laid the groundwork for advancing our understanding of HPA-axis regulation by stress-derived steroid hormones and their neuroactive metabolites (termed neurosteroids), which are potent allosteric modulators of GABAA receptor function in the central nervous system. This review will describe what is known about neurosteroid modulation of the HPA-axis in response to both acute and chronic stress, particularly with respect to the current state of our knowledge of this process in humans. Implications of this research to the development of human stress related illness are discussed in the context of two human stress-related psychiatric disorders - major depressive disorder and premenstrual dysphoric disorder. Neurosteroid-mediated HPA-axis dysregulation is a potential pathophysiologic mechanism which may cross traditional psychiatric diagnostic classifications. Future research directions are identified.
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影响因子：
2.3
作者：
Childs, Emma;Van Dam, Nicholas T.;de Wit, Harriet
通讯作者：
de Wit, Harriet
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3.1
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影响因子：
10.6
作者：
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通讯作者：
Rubinow, DR