Neurosteroid Levels in the Orbital Frontal Cortex of Subjects with PTSD and Controls: A Preliminary Report.
Neurosteroid Levels in the Orbital Frontal Cortex of Subjects with PTSD and Controls: A Preliminary Report.
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DOI：
10.1177/2470547019838570
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发表时间：
2019-01-01
期刊：
影响因子：
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通讯作者：
Williamson, Douglas E
中科院分区：
文献类型：
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作者：
Cruz, Dianne A;Glantz, Leisa A;Williamson, Douglas E
背景资料：神经甾体介导应激信号传导，并且在临床前和临床研究中均涉及创伤后应激障碍（PTSD）的发病机制。与对照组相比，PTSD受试者表现出外周血和脑脊液中神经类固醇水平的改变以及内侧眶额叶皮质（mOFC）的活动减退。因此，本研究的目的是比较PTSD受试者（n = 18）和对照组（n = 35）mOFC中的神经类固醇水平。从新鲜冷冻的mOFC中解剖灰质，并测定神经甾体双烯醇酮、别孕烯醇酮、孕烯醇酮、表别孕烯醇酮、表孕烯醇酮、四氢脱氧皮质酮、采用气相色谱-串联质谱法（GC-MS/MS）测定了结果：对未调整水平的分析显示，患有PTSD的男性的别孕烯醇酮水平显著降低，与对照组相比，患有PTSD的男性和女性具有显著增加的双烯醇酮水平（p = 0.03）。在控制了年龄、死亡时间和吸烟状况后，结果显示，患有创伤后应激障碍的男性的雄酮水平显著降低，（t46 = 2.37，p = 0.02）与对照相比，患有PTSD的男性和女性具有显著增加的孕烯醇酮水平。（t46 =-2.25，p = 0.03）相对于控制femines.Conclusions：据我们所知，这是第一次报告的神经类固醇水平在死后脑组织的受试者与创伤后应激障碍。虽然在其他脑区和更大的受试者队列中需要复制，但结果表明mOFC中PTSD男性和PTSD女性中的别孕烯醇酮和雄酮失调。
Background: Neurosteroids mediate stress signaling and have been implicated in the pathogenesis of post-traumatic stress disorder (PTSD) in both preclinical and clinical studies. Compared to controls, subjects with PTSD exhibit altered neurosteroid levels in peripheral blood and cerebrospinal fluid as well as hypoactivity in the medial orbital frontal cortex (mOFC). Therefore, the aim of this study was to compare neurosteroid levels in the mOFC of subjects with PTSD (n = 18) and controls (n = 35).Methods: Gray matter was dissected from fresh-frozen mOFC, and levels of the neurosteroids pregnenolone, allopregnanolone, pregnanolone, epiallopregnanolone, epipregnanolone, tetrahydrodeoxycorticosterone, and androsterone were determined by gas chromatography - tandem mass spectrometry (GC/MS/MS).Results: Analyses of unadjusted levels revealed that males with PTSD had significantly decreased levels of allopregnanolone (p = 0.03) compared to control males and females with PTSD had significantly increased levels of pregnenolone (p = 0.03) relative to control females. After controlling for age, postmortem interval, and smoking status, results showed that males with PTSD had significantly decreased levels of androsterone (t46 = 2.37, p = 0.02) compared to control males and females with PTSD had significantly increased levels of pregnanolone (t46 = -2.25, p = 0.03) relative to control females.Conclusions: To our knowledge, this is the first report of neurosteroid levels in postmortem brain tissue of subjects with PTSD. Although replication is required in other brain regions and in a larger cohort of subjects, the results suggest a dysregulation of allopregnanolone and androsterone in males with PTSD and pregnanolone in females with PTSD in the mOFC.