The Effects of Stress Exposure on Prefrontal Cortex: Translating Basic Research into Successful Treatments for Post-Traumatic Stress Disorder.
The Effects of Stress Exposure on Prefrontal Cortex: Translating Basic Research into Successful Treatments for Post-Traumatic Stress Disorder.
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DOI：
10.1016/j.ynstr.2014.10.002
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发表时间：
2015-01-01
影响因子：
5
通讯作者：
Connor, Daniel F
中科院分区：
文献类型：
--
作者：
Arnsten, Amy F T;Raskind, Murray A;Taylor, Fletcher B;Connor, Daniel F
对动物应激反应的神经生物学研究已经成功地为人类创伤后应激障碍（PTSD）提供了新的治疗方法。基础研究发现，在压力下释放高水平的儿茶酚胺会迅速损害前额叶皮层（PFC）自上而下的认知功能，同时加强杏仁核和基底神经节的情绪和习惯反应。慢性应激暴露导致PFC中的树突萎缩、杏仁核中的树突延伸以及去甲肾上腺素能（NE）系统的加强。在应激过程中高水平的NE释放会激活低亲和力的α-1肾上腺素受体（可能还有β-1肾上腺素受体），这会迅速减少PFC神经元的放电，但会加强杏仁核的功能。相比之下，在非应激条件下，中等水平的NE释放与更高亲和力的α-2A受体结合，这增强了PFC，削弱了杏仁核，并调节NE细胞放电。因此，α-1受体阻断剂或α-2A受体刺激剂可以在应激期间保护PFC功能。PTSD患者有PFC功能障碍的迹象。临床研究发现，用哌唑嗪阻断α-1受体，或用胍法辛或可乐定刺激α-2A受体，可以有效减轻PTSD的症状。安慰剂对照试验表明，哌唑嗪对患有PTSD的退伍军人、现役士兵和平民有帮助，包括改善PFC症状，如注意力和冲动控制受损。开放标签研究表明，胍法辛可能特别有助于治疗经历过创伤的儿童和青少年。因此，了解压力反应的神经生物学已经开始帮助患有压力障碍的患者。对动物的研究揭示了前额叶皮层在压力下是如何“离线”的。前额叶皮质功能受α2A-保护，但受α1-肾上腺素受体损害。基于这项研究，α1受体阻滞剂和α2A受体激动剂现在用于治疗PTSD。
Research on the neurobiology of the stress response in animals has led to successful new treatments for Post-Traumatic Stress Disorder (PTSD) in humans. Basic research has found that high levels of catecholamine release during stress rapidly impair the top-down cognitive functions of the prefrontal cortex (PFC), while strengthening the emotional and habitual responses of the amygdala and basal ganglia. Chronic stress exposure leads to dendritic atrophy in PFC, dendritic extension in the amygdala, and strengthening of the noradrenergic (NE) system. High levels of NE release during stress engage low affinity alpha-1 adrenoceptors, (and likely beta-1 adrenoceptors), which rapidly reduce the firing of PFC neurons, but strengthen amygdala function. In contrast, moderate levels of NE release during nonstress conditions engage higher affinity alpha-2A receptors, which strengthen PFC, weaken amygdala, and regulate NE cell firing. Thus, either alpha-1 receptor blockade or alpha-2A receptor stimulation can protect PFC function during stress. Patients with PTSD have signs of PFC dysfunction. Clinical studies have found that blocking alpha-1 receptors with prazosin, or stimulating alpha-2A receptors with guanfacine or clonidine can be useful in reducing the symptoms of PTSD. Placebo-controlled trials have shown that prazosin is helpful in veterans, active duty soldiers and civilians with PTSD, including improvement of PFC symptoms such as impaired concentration and impulse control. Open label studies suggest that guanfacine may be especially helpful in treating children and adolescents who have experienced trauma. Thus, understanding the neurobiology of the stress response has begun to help patients with stress disorders. Research in animals has revealed how prefrontal cortex goes “off-line” during stress. Prefrontal cortical function is protected by α2A-, but impaired by α1-adrenoceptors. Based on this research, α1 blockers and α2A agonists are now in use to treat PTSD.