Elevated brain cannabinoid CB1 receptor availability in post-traumatic stress disorder: a positron emission tomography study.
Elevated brain cannabinoid CB1 receptor availability in post-traumatic stress disorder: a positron emission tomography study.
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DOI：
10.1038/mp.2013.61
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发表时间：
2013-09
影响因子：
11
通讯作者：
Huang, Y.
中科院分区：
文献类型：
--
作者：
Neumeister, A.;Normandin, M. D.;Pietrzak, R. H.;Piomelli, D.;Zheng, M. Q.;Gujarro-Anton, A.;Potenza, M. N.;Bailey, C. R.;Lin, S. F.;Najafzadeh, S.;Ropchan, J.;Henry, S.;Corsi-Travali, S.;Carson, R. E.;Huang, Y.
内源性大麻素及其参与的 1 型大麻素受体 (CB1) 与创伤后应激障碍 (PTSD) 的动物模型有关。然而，它们的具体作用尚未在创伤后应激障碍患者中进行研究。在此，我们提出了一项使用正电子发射断层扫描 (PET) 和 CB1 选择性放射性配体 [11C]OMAR 对 PTSD 个体、有终生创伤史的健康对照（创伤对照 [TC]）和没有此类历史的健康对照（健康对照 [HC]）进行的体内成像研究。具有非战斗创伤史的未经治疗的 PTSD 个体 (N=25)、TC (N=12) 和 HC (N=23) 参加了磁共振 (MR) 成像扫描和使用 CB1 受体拮抗剂放射性示踪剂 [11C]OMAR 的静息 PET 扫描，该扫描测量与 CB1 受体可用性线性相关的分布体积 (VT)。还评估了花生四烯酸乙醇胺、2-花生四烯酰甘油 (2-AG)、油酰乙醇酰胺 (OEA)、棕榈酰乙醇酰胺 (PEA) 和皮质醇的外周水平。在 PTSD 组中，相对于 HC 和 TC 组，我们发现全脑 [11C]OMAR VT 值升高（F(2,53)=7.96，p=.001；分别高出 19.5% 和 14.5%），这在女性中最为明显（F(1,53)=5.52，p=.023）。相对于 TC 组（降低 53.1%）和 HC 组（降低 58.2%），PTSD 组的 Anandamide 浓度降低。相对于 HC 组，PTSD 组和 TC 组的皮质醇水平较低。共同检查的三种生物标志物——OMAR VT、anandamide 和皮质醇——正确分类了近 85% 的 PTSD 病例。这些结果表明，异常的 CB1 受体介导的 anandamide 信号传导与 PTSD 的病因学有关，并为开发针对这种疾病的新型循证药物疗法提供了一个有前途的神经生物学模型。
Endocannabinoids and their attending cannabinoid type 1 receptor (CB1) have been implicated in animal models of posttraumatic stress disorder (PTSD). However, their specific role has not been studied in people with PTSD. Herein, we present an in vivo imaging study using positron emission tomography (PET) and the CB1-selective radioligand [11C]OMAR in individuals with PTSD, and healthy controls with lifetime histories of trauma (trauma controls [TC]) and those without such histories (healthy controls [HC]). Untreated individuals with PTSD (N=25) with non-combat trauma histories, and TC (N=12) and HC (N=23) participated in a magnetic resonance (MR) imaging scan and a resting PET scan with the CB1 receptor antagonist radiotracer [11C]OMAR, which measures volume of distribution (VT) linearly related to CB1 receptor availability. Peripheral levels of anandamide, 2-arachidonoylglycerol (2-AG), oleoylethanolamide (OEA), palmitoylethanolamide (PEA), and cortisol were also assessed. In the PTSD group, relative to the HC and TC groups, we found elevated brain-wide [11C]OMAR VT values (F(2,53)=7.96, p=.001; 19.5% and 14.5% higher, respectively) which were most pronounced in women (F(1,53)=5.52, p=.023). Anandamide concentrations were reduced in the PTSD relative to the TC (53.1% lower) and HC (58.2% lower) groups. Cortisol levels were lower in the PTSD and TC groups relative to the HC group. Three biomarkers examined collectively—OMAR VT, anandamide, and cortisol—correctly classified nearly 85% of PTSD cases. These results suggest that abnormal CB1 receptor-mediated anandamide signaling is implicated in the etiology of PTSD, and provide a promising neurobiological model to develop novel, evidence-based pharmacotherapies for this disorder.
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DOI：
10.1523/jneurosci.4283-10.2010
发表时间：
2010-11-10
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Hill MN;Patel S;Campolongo P;Tasker JG;Wotjak CT;Bains JS
通讯作者：
Bains JS
影响因子：
3.5
作者：
de Jong, Hugo W. A. M.;van Velden, Floris H. P.;Lammertsma, Adriaan A.
通讯作者：
Lammertsma, Adriaan A.
影响因子：
3.8
作者：
GANDELMAN, MS;BALDWIN, RM;INNIS, RB
通讯作者：
INNIS, RB
影响因子：
6.1
作者：
Beyer, Chad E.;Dwyer, Jason M.;Whiteside, Garth T.
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：
Tarter, Ralph