Girgenti Matthew J, Hare Brendan D, Ghosal Sriparna, Duman Ronald S
Department of Psychiatry, Laboratory of Molecular Psychiatry, Center for Genes and Behavior, Yale University School of Medicine, New Haven, CT, 06508, USA.
Curr Psychiatry Rep. 2017 Sep 25;19(11):85. doi: 10.1007/s11920-017-0841-3.
Posttraumatic stress disorder (PTSD) is characterized by hyperarousal and recurrent stressful memories after an emotionally traumatic event. Extensive research has been conducted to identify the neurobiological determinants that underlie the pathophysiology of PTSD. In this review, we examine evidence regarding the molecular and cellular pathophysiology of PTSD focusing on two primary brain regions: the vmPFC and the amygdala.
This discussion includes a review of the molecular alterations related to PTSD, focusing mainly on changes to glucocorticoid receptor signaling. We also examine postmortem gene expression studies that have been conducted to date and the molecular changes that have been observed in peripheral blood studies of PTSD patients. Causal, mechanistic evidence is difficult to obtain in human studies, so we also review preclinical models of PTSD. Integration of peripheral blood and postmortem studies with preclinical models of PTSD has begun to reveal the molecular changes occurring in patients with PTSD. These findings indicate that the pathophysiology of PTSD includes disruption of glucocorticoid signaling and inflammatory systems and occurs at the level of altered gene expression. We will assess the impact of these findings on the future of PTSD molecular research.
创伤后应激障碍（PTSD）的特征是在经历情感创伤事件后出现过度警觉和反复出现的应激性记忆。人们已经进行了广泛的研究，以确定PTSD病理生理学背后的神经生物学决定因素。在本综述中，我们研究了关于PTSD分子和细胞病理生理学的证据，重点关注两个主要脑区：腹内侧前额叶皮质（vmPFC）和杏仁核。
本次讨论包括对与PTSD相关的分子改变的综述，主要关注糖皮质激素受体信号传导的变化。我们还研究了迄今为止进行的尸检基因表达研究以及在PTSD患者外周血研究中观察到的分子变化。在人体研究中很难获得因果关系和机制性证据，因此我们也综述了PTSD的临床前模型。将外周血和尸检研究与PTSD临床前模型相结合，已开始揭示PTSD患者发生的分子变化。这些发现表明，PTSD的病理生理学包括糖皮质激素信号传导和炎症系统的破坏，并且发生在基因表达改变的水平。我们将评估这些发现对PTSD分子研究未来的影响。
