焦虑障碍生化基础120206_Herbert120217PPT课件.ppt

焦虑障碍 神经生化基础与临床实践;神经递质及其受体作用与 焦虑障碍发病机制;焦虑形成是体质因素和环境因素共同作用的结果，焦虑表型－恐惧和忧虑分别在大脑有两个环路：恐惧与杏仁核环路相关；忧虑与皮层－纹状体－丘脑－皮层环路相关。神经递质如GABA、5-HT、NE、DA、皮质醇等参与了焦虑的发病机制 ;;Stephen M.Stahl. Stahl’s Essential Psychopharmacology Neuroscientific Basis and Practical Applications.New York,Cambridge University Press,2008:732-741.;GABA受体 ;焦虑与GABA水平降低相关;惊恐障碍与GABA水平降低相关;BDZ-GABAA受体参与PD的发病机制;Gregor Hasler; Altered cerebral gamma-aminobutyric acid type A-benzodiazepine receptor binding in panic disorder determined by [11C]flumazenil positron emission tomography. Arch Gen Psychiatry. 2008;65(10):1166-1175;受体水平降低区域包括：双侧额上回、右中央前回、双侧额中回、双侧额内侧叶、双侧颞中回、右钩回、右梭状回、左侧颞下回、左侧海马、右侧顶上小叶、左楔叶、双侧枕中回、左侧枕下回、左侧尾状核、双侧丘脑 （SPM和手动ROI法检测）;其它焦虑障碍与GABA-BZ受体水平的关系;苯二氮卓类药物作用机制;病理性焦虑可能由于杏仁核环路的过度激活引起;;;;;;动物学研究： 5-HT1A受体基因敲除小鼠发生焦虑 (Elena Akimova, et al. Biol Psychiatry 2009; 66: 627-635) 5-HT1A受体结合率降低，应激相关的神经精神障碍易损性增加 (Spinelli S et al. Effects of early-life stress on serotonin(1A) receptors in juvenile Rhesus monkeys measured by positron emission tomography. Biol Psychiatry 2010; 67(12): 1146-53) 人体学研究： 健康志愿者脑内5-HT1A 受体水平与其焦虑水平负相关 (Tauscher et al. Am J Psychiat. 2001,158(8):1326-1328) 眶额叶5-HT1A受体亲和力与攻击性负相关(Parsey RV, Oquendo MA, Simpson NR, et al. Effects of sex, age, and aggressive traits in man on brain serotonin 5-HT1A receptor binding potential measured by PET using [C-11]WAY-100635. Brain Res. 2002, 954(2):173-82.) PD患者脑内5-HT1A受体结合率降低 (Neumeister A et al. Reduced serotonin type 1A receptor binding in panic disorder. J Neurosci 2004; 24(3): 589-91) 惊恐障碍患者在有效治疗前，其5-HT1A受体结合力下降 (Nash, Grasby, Nutt Br J Psychiatry 2008;193(3):229-34) SAD患者5-HT1A受体结合力下降 (Lanzenberger RR, Mitterhauser M, Spindelegger C, et al. Biol Psychiatry 2007; 61: 1081-1089);;脑5-HT1A受体亲和力与焦虑程度负相关---健康人;注：以Brown Goodwin量表评价攻击性指数。;Neumeister A et al. Reduced serotonin type 1A receptor binding in panic disorder. J Neurosci 2004; 24(3): 589-91;惊恐障碍大脑焦虑环路5-HT1A受体降低;Lanzenberger RR, , Mitterhauser M, Spindelegger C, et al. Biol Psychiatry 2007; 61: 10