A Two-Hit Model of The Biological Origin of Posttraumatic Stress Disorder (PTSD)
A Two-Hit Model of The Biological Origin of Posttraumatic Stress Disorder (PTSD)
复制标题
创伤后应激障碍 (PTSD) 生物学起源的二次打击模型
DOI：
10.29245/2578-2959/2018/5.1165
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
B. Engdahl
中科院分区：
文献类型：
--
作者：
A. Georgopoulos;Lisa M. James;P. Christova;B. Engdahl
创伤后应激障碍（PTSD）是一种使人衰弱的疾病，可以在暴露于创伤事件后发展。虽然创伤后应激障碍的原因是已知的，但其发展的大脑机制仍然未知，特别是为什么它在某些人中出现而不是在其他人中。大多数关于创伤后应激障碍的研究都涉及其心理学和大脑机制，包括侵入性记忆，恐惧和回避（参见参考文献1关于创伤后应激障碍研究的广泛报道）。在这里，我们的重点，而不是创伤后应激障碍的起源，即其发展背后的神经机制。具体来说，我们提出了一个两次打击模型的创伤后应激障碍的发展，与以下组件。(a)第一次打击是神经免疫攻击，作为预先存在的状况，第二次打击是由创伤事件诱导的强烈的神经递质性神经传递;（B）介导这两次打击的作用的关键分子是细胞间粘附分子5（ICAM-5），发现其在PTSD 2中差异表达。ICAM-5通过神经免疫挑战3，4和突触能神经传递5，6激活，它进一步增强突触能传递6，并且除了免疫调节功能之外，对突触形成和神经可塑性发挥有效作用3，4，7;以及（c）关于所涉及的神经网络，所涉及最多的脑区域是内侧颞皮质区域，以及相互连接的皮质和皮质下区域8 -10。我们假设，在存在持续神经免疫激发的情况下，由创伤事件诱导的那些区域中的强烈神经递质传递的净结果导致ICAM-5水平增加，其进一步增强神经递质传递，从而导致具有高度相关神经相互作用的神经网络状态，如在功能性神经成像研究中观察到的8 -10。我们假设这样一个“锁定”网络是创伤后应激障碍中侵入性再体验的基础，并维持相关的心理学，如恐惧和回避。
Posttraumatic stress disorder (PTSD) is a debilitating disorder that can develop following exposure to a traumatic event. Although the cause of PTSD is known, the brain mechanisms of its development remain unknown, especially why it arises in some people but not in others. Most of the research on PTSD has dealt with psychological and brain mechanisms underlying its symptomatology, including intrusive memories, fear and avoidance (see ref.1 for a broad coverage of PTSD research)1. Here we focus, instead, on the origin of PTSD, namely on the neural mechanisms underlying its development. Specifically, we propose a two-hit model for PTSD development, with the following components. (a) The 1st hit is a neuroimmune challenge, as a preexisting condition, and the 2nd hit is intense glutamatergic neurotransmission, induced by the traumatic event; (b) the key molecule that mediates the effects of these two hits is intercellular adhesion molecule 5 (ICAM-5) which was found to be differentially expressed in PTSD2. ICAM-5 is activated by neuroimmune challenge3,4 and glutamatergic neurotransmission5,6, it further enhances glutamatergic transmission6, and exerts a potent effect on synapse formation and neural plasticity, in addition to immunoregulatory functions3,4,7; and (c) with respect to the neural network(s) involved, the brain areas most involved are medial temporal cortical areas, and interconnected cortical and subcortical areas8–10. We hypothesize that the net result of intense glutamatergic transmission in those areas induced by a traumatic event in the presence of ongoing neuroimmune challenge leads to increased levels of ICAM-5 which further enhances glutamatergic transmission and thus leads to a state of a neural network with highly correlated neural interactions, as has been observed in functional neuroimaging studies8–10. We assume that such a “locked-in” network underlies the intrusive re-experiencing in PTSD and maintains associated symptomatology, such as fear and avoidance.
影响因子：
25.8
作者：
Eraly, Satish A.;Nievergelt, Caroline M.;Maihofer, Adam X.;Barkauskas, Donald A.;Biswas, Nilima;Agorastos, Agorastos;O'Connor, Daniel T.;Baker, Dewleen G.
通讯作者：
Baker, Dewleen G.
影响因子：
--
作者：
KESSLER, RC;SONNEGA, A;NELSON, CB
通讯作者：
NELSON, CB
影响因子：
3.3
作者：
Kilpatrick, Dean G.;Resnick, Heidi S.;Milanak, Melissa E.;Miller, Mark W.;Keyes, Katherine M.;Friedman, Matthew J.
通讯作者：
Friedman, Matthew J.