STUDIES IN POST TRAUMATIC STRESS DISORDER (PTSD), PANIC DISORDER & SOCIAL PHOBIA

该项目由几个临床研究组成，旨在阐明创伤后应激障碍、恐慌症和社交恐惧症的神经生物学，并研究这些严重焦虑症的潜在新治疗方法。研究涉及神经内分泌和行为挑战与焦虑神经肽激动剂pentagastrin的目的是确定外周和中枢胆囊收缩素在正常和病理焦虑状态中的作用。迄今为止，我们已经确定静脉注射戊加司汀会导致社交恐惧症和恐慌症患者的焦虑和综合征特异性症状增加，并且患有这些焦虑症的患者对戊加司汀的焦虑效应比健康志愿者更敏感。早期数据表明，PTSD患者在静脉注射戊胃泌素后也会出现综合征特异性症状（即闪回）。昂丹司琼是一种5-HT3拮抗剂，在动物模型中阻断CCK激动剂的焦虑作用，并没有减弱pentagastrin对焦虑症患者的作用。一项正在进行的研究的早期结果也表明，选择性5 -羟色胺再摄取抑制剂（SSRIs）对恐慌症和社交恐惧症都有治疗作用，但SSRIs并不能减弱静脉注射戊胃泌素的效果。创伤后应激障碍患者的试验数据表明，加巴喷丁可能作为创伤后应激障碍慢性治疗的辅助药物。初步研究表明，右额叶1hz反复经颅磁刺激（rTMS）治疗创伤后应激障碍是有希望的，一项随机对照试验已经启动。1hz rTMS的数据显示，治疗两周后，正常志愿者的脑代谢急剧减少，抑郁症患者的血流量减少，初步数据显示，PTSD患者也有同样的效果。这些影响与PTSD症状改善的关系仍有待阐明。

This project is comprised of several clinical research studies designed to elucidate the neurobiology of PTSD, panic disorder, and social phobia, and to investigate potential new treatments for these serious anxiety disorders. Studies involving neuroendocrine and behavioral challenges with the anxiogenic neuropeptide agonist pentagastrin are aimed at determining the role of peripheral and central cholecystokinin in normal and pathological anxiety states. To date, we have determined that intravenous pentagastrin leads to increased anxiety and syndrome-specific symptoms in patients with social phobia and panic disorder, and that patients with these anxiety disorders are more sensitive to the anxiogenic effects of pentagastrin than healthy volunteers. Early data suggest that patients with PTSD also develop syndrome-specific symptoms (i.e., flashbacks) upon pharmacological challenge with intravenous pentagastrin. Ondansetron, a 5-HT3 antagonist that blocks the anxiogenic effects of CCK agonists in animal models, did not attenuate the effects of pentagastrin in patients with anxiety disorders. Early results from an ongoing study also suggest that treatment with selective serotonin reuptake inhibitors (SSRIs) is therapeutic in both panic disorder and social phobia, but that SSRIs do not attenuate the effects of intravenous pentagastrin. Pilot data in patients with PTSD suggest that gabapentin may have utility as an adjunctive medication in the chronic treatment of PTSD. Preliminary studies of right frontal 1 Hz repeated transcranial magnetic stimulation (rTMS) of the brain for the treatment of PTSD are promising, and a randomized, controlled trial has been initiated. Data with 1 Hz rTMS suggest that it acutely reduces cerebral metabolism in normal volunteers and reduces blood flow in depressed patients treated for two weeks, and preliminary data suggest the same effect in patients with PTSD. The relationship of these effects to improvement in PTSD symptoms remains to be elucidated.