Glucocorticoid Mechanisms of Functional Connectivity Changes in Stress-Related Neuropsychiatric Disorders.
Glucocorticoid Mechanisms of Functional Connectivity Changes in Stress-Related Neuropsychiatric Disorders.
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DOI：
10.1016/j.ynstr.2014.10.008
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发表时间：
2015-01-01
影响因子：
5
通讯作者：
Liston, Conor
中科院分区：
文献类型：
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作者：
Hall, Baila S;Moda, Rachel N;Liston, Conor
压力——尤其是慢性、无法控制的压力——是许多神经精神疾病的重要危险因素。潜在的机制是复杂且多因素的，但它们涉及皮质微电路内和跨神经解剖学分布的大脑网络的神经元连接的结构和功能测量的相关变化。在这里，我们回顾了来自动物模型和人类神经影像学研究的证据，这些证据表明与压力相关的功能连接变化在创伤后应激障碍、抑郁症和其他神经精神疾病的发病机制中。分布式网络中皮质皮质连接性的功能磁共振成像测量的变化可能是由在前额皮质、海马体和其他脆弱大脑区域中观察到的特定结构改变引起的。这些作用部分是由糖皮质激素介导的，糖皮质激素是肾上腺响应应激源而释放的，并且与昼夜节律同步振荡。最近的研究表明，昼夜节律的糖皮质激素振荡可以平衡学习后和发育过程中的突触形成和修剪，而慢性压力会破坏这种平衡。最后，我们考虑了糖皮质激素振荡紊乱如何导致易感个体抑郁和创伤后应激障碍的病理生理学，以及昼夜节律紊乱如何影响非精神病人群，包括经常旅行的人、轮班工人和接受自身免疫性疾病治疗的患者。
Stress—especially chronic, uncontrollable stress—is an important risk factor for many neuropsychiatric disorders. The underlying mechanisms are complex and multifactorial, but they involve correlated changes in structural and functional measures of neuronal connectivity within cortical microcircuits and across neuroanatomically distributed brain networks. Here, we review evidence from animal models and human neuroimaging studies implicating stress-associated changes in functional connectivity in the pathogenesis of PTSD, depression, and other neuropsychiatric conditions. Changes in fMRI measures of corticocortical connectivity across distributed networks may be caused by specific structural alterations that have been observed in the prefrontal cortex, hippocampus, and other vulnerable brain regions. These effects are mediated in part by glucocorticoids, which are released from the adrenal gland in response to a stressor and also oscillate in synchrony with diurnal rhythms. Recent work indicates that circadian glucocorticoid oscillations act to balance synapse formation and pruning after learning and during development, and chronic stress disrupts this balance. We conclude by considering how disrupted glucocorticoid oscillations may contribute to the pathophysiology of depression and PTSD in vulnerable individuals, and how circadian rhythm disturbances may affect non-psychiatric populations, including frequent travelers, shift workers, and patients undergoing treatment for autoimmune disorders.