Translational evidence for a role of endocannabinoids in the etiology and treatment of posttraumatic stress disorder.
Translational evidence for a role of endocannabinoids in the etiology and treatment of posttraumatic stress disorder.
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DOI：
10.1016/j.psyneuen.2014.10.012
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发表时间：
2015-01
影响因子：
3.7
通讯作者：
Pietrzak, Robert H.
中科院分区：
文献类型：
--
作者：
Neumeister, Alexander;Seidel, Jordan;Ragen, Benjamin J.;Pietrzak, Robert H.
创伤后应激障碍（PTSD）是一种普遍的、慢性的、致残的焦虑症，可能在暴露于创伤性事件后发展。尽管PTSD具有重要的公共卫生意义，但人们对其病因或病理生理学的了解相对较少，迄今为止的药物治疗发展主要是机会性的，而不是基于机制的。最近，越来越多的证据表明，内源性大麻素系统与PTSD的病因有关，并且该系统中的靶点被认为适合于治疗开发。在此，我们描述了来自转化研究的证据，证明内源性大麻素系统在PTSD病因学中的相关性。我们还展示了与治疗发展相关的机制。多项研究有令人信服的证据表明，PTSD患者内源性大麻素的可用性降低。脑成像研究表明，应激障碍与异常威胁处理和焦虑唤醒症状有关，其分子适应与大麻素1型（CB1）受体可用性升高有关。特别相关的证据显示创伤后应激障碍中内源性大麻素anandamide水平降低和CB1受体可获得性代偿性增加，以及创伤幸存者中杏仁核中CB1受体可获得性增加与异常威胁处理以及高觉醒严重程度增加之间的关联，但没有烦躁症状。鉴于高觉醒症状是PTSD致残方面的关键驱动因素，如情绪麻木或自杀，针对PTSD患者这一特定症状群的新型、基于机制的药物治疗可能有助于减轻该疾病的慢性和发病率。
Posttraumatic stress disorder (PTSD) is a prevalent, chronic, and disabling anxiety disorder that may develop following exposure to a traumatic event. Despite the public health significance of PTSD, relatively little is known about the etiology or pathophysiology of this disorder, and pharmacotherapy development to date has been largely opportunistic instead of mechanism-based. Recently, an accumulating body of evidence has implicated the endocannabinoid system in the etiology of PTSD, and targets within this system are believed to be suitable for treatment development. Herein, we describe evidence from translational studies arguing for the relevance of the endocannabinoid system in the etiology of PTSD. We also show mechanisms relevant for treatment development. There is convincing evidence from multiple studies for reduced endocannabinoid availability in PTSD. Brain imaging studies show molecular adaptations with elevated cannabinoid type 1 (CB1) receptor availability in PTSD which is linked to abnormal threat processing and anxious arousal symptoms. Of particular relevance is evidence showing reduced levels of the endocannabinoid anandamide and compensatory increase of CB1 receptor availability in PTSD, and an association between increased CB1 receptor availability in the amygdala and abnormal threat processing, as well as increased severity of hyperarousal, but not dysphoric symptomatology, in trauma survivors. Given that hyperarousal symptoms are the key drivers of more disabling aspects of PTSD such as emotional numbing or suicidality, novel, mechanism-based pharmacotherapies that target this particular symptom cluster in patients with PTSD may have utility in mitigating the chronicity and morbidity of the disorder.
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影响因子：
3.7
作者：
Ditlevsen DN;Elklit A
通讯作者：
Elklit A
影响因子：
--
作者：
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通讯作者：
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4.6
作者：
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通讯作者：
Whiteside, Garth T.
影响因子：
4.4
作者：
Cornelius, Jack R.;Kirisci, Levent;Tarter, Ralph
通讯作者：
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