抑郁症神经基础研究

Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,抑郁症的神经生物学,:,精神与躯体的关联,浙医二院 李惠春,内容,抑郁症,错综复杂的病情，兼有情感症状和躯体症状,1,慢性、持续、进展性病程,1,2,伴有大脑皮质的功能和结构改变,2,3,神经营养因子可能是介导这些改变的关键因素,4,抗抑郁药治疗可能恢复原有的生理特性,5,临床痊愈是治疗的首要目标,6,7,1,APA.,DSM-IV-TR,;2000:352,356.,2,Maletic V(2005),Prim Psychiatry 12(suppl 10):7-9;,3,Apkarian AV et al.(2004),J Neurosci 24(46):10410-10415;,4,Castrn et al.(2006),Curr Opin Pharmacol 6:1-4;,5,Duric V,McCarson KE(2005),Neuroscience 133(3):999-1006;,6,Keller MB et al.(1992),Arch Gen Psychiatry 49(10):809-816;,7,American Psychiatric Association(APA)(2000),Am J Psychiatry 157(4 suppl):1-45,多重核心症状和关联症状,情感症状,罪恶感,自杀意念,缺乏兴趣,悲伤,躯体症状,缺乏精力,注意力降低,食欲改变,睡眠改变,精神运动技能改变,关联症状,郁闷,强迫性穷思竭虑,易激惹,对躯体健康过度担忧,疼痛,易哭,焦虑或恐惧,APA.,DSM-IV-TR,;2000:352,356.,抑郁症患者的相关疼痛症状的患病率有多高,?,14,项有关抑郁症患者疼痛症状的专项研究中的平均患病率数据,Bair MJ,et al.,Arch Intern Med.,2003;163:2433-2445.,抑郁症不伴疼痛症状,35%,抑郁症伴疼痛症状,65%,精神科与通科的科室差别对患病率没有影响,抑郁患者,有一些研究同时探寻了抑郁症与下列疼痛症状,:,头痛,背痛,颈痛,肢端,/,关节痛,胸痛,骨盆痛,腹痛,全身痛,亚太地区疼痛症状的发生率,国家,/,地区,PPS+,PPS-,Total,PPS+Frequency(95%CI),全部,471,438,909,51.8%(48.5%-55.1%),中国,(,大陆,),105,194,299,35.1%(29.7%-40.8%),中国,(,香港,),66,24,90,73.3%(63.0%-82.1%),韩国,91,107,198,46.0%(38.9%-53.2%),马来西亚,63,35,98,64.3%(54.0%-73.7%),新加坡,12,18,30,40.0%(22.7%-59.4%),台湾,134,60,194,69.1%(62.1%-75.5%),虽然中国病人,PPS,的发生率高,但仍低于其它亚洲国家,/,地区,正常人群，完全没有抑郁,边缘抑郁,轻度抑郁,中度抑郁,重度抑郁,难治性抑郁,Fava M,et al.J Clin Psychiatry 2004;65:521-530,疼痛性躯体症状与抑郁的严重程度,疼痛的严重程度与抑郁的严重程度成正相关,痊愈,急性和持续性应激源,1,2,抑郁发作的严重程度和病程,1,2,既往治疗无效史,2,焦虑,1,躯体症状,3,人格障碍,2,物质滥用,4,内科疾病,4,复发,既往发作的严重程度、次数和病程,5,症状控制不充分,(,亚综合征症状,),5,共患焦虑症,和物质滥用,5,躯体症状,6,应激事件,7,应对策略不足,7,可能阻碍临床痊愈的因素对复发有预测作用,1,Parker G et al.(2000),Aust N Z J Psychiatry 34(1):56-64;,2,Rush AJ et al.(2006),Neuropsychopharmacology 31(9):1841-1853;,3,Fava M(2003),J Clin Psychiatry 64(suppl 7):24-28;,4,Keller MB(2005),J Clin Psychiatry 66(suppl 8):5-12;,5,Keller MB(1999),J Clin Psychiatry 60(suppl 17):41-48;,6,Ohayon MM(2004),J Clin Psychiatry 65(suppl 12):5-9;,7,Bockting CL et al.(2006),J Clin Psychiatry 67(5):747-755,躯体症状是妨碍获得临床治愈的主要障碍之一,抑郁症的残留症状中，,94%,是躯体症状,注：用,HAM-D,17,第,13,项,(,躯体症状,/,全身症状,),来评估躯体症状,Adapted from Paykel ES,et al.Psychol Med.1995;25(6):1171-1180,抑郁症的残留症状和发作次数可能影响病程,任一抑郁发作首次前瞻性复燃前的稳定周数,0.6,0.8,0.4,0.2,1.0,0,生存率分布函数,0,50,100,150,200,250,300,350,400,450,500,无症状康复,1-3,次发作,(N=121),224.0,无症状康复,3,次以上发作,(N=34),79.0,残留,SSD,康复,1-3,次发作,(N=57),34.0,残留,SSD,康复,3,次以上发作,(N=25),28.0,中位病稳,周数,SSD=,抑郁症的亚综合征症状,;,生存率分布函数,=,在给定的时间间隔中生存（病稳无复燃）的累计病例比例,.,Judd LL,et al.,J Affect Disord.,1998;50(2-3):97-108,.,抗抑郁药治疗对躯体症状和情感症状并不等效,基线,1,个月,3,个月,6,个月,9,个月,ARTIST,SSRI,治疗随机试验,改善,治疗效应指数,情感症状,躯体症状,自我感觉良好,非躯体性抑郁症状,非疼痛性躯体症状,疼痛性躯体症状,抑郁症和疼痛相关的神经生物学基础,“网络,”,层面,:,神经回路失调,功能改变,结构改变,神经内分泌、自主神经及免疫失调,细胞及亚细胞层面,对下列因素的影响,:,细胞内信号传递,基因转录,神经营养支持,遗传易患性,应激,损伤,神经精神症状,情感,认知,行为,躯体,全身表现,Sheline YI,et al.,Biol Psychiatry.,2001;50(9):651.,;,Raison CL,et al.,Trends Immunol.,2006;27(1):24.,;,Gatt JM,et al.,J Integr Neurosci.,2007;6(1):75.,;,Carlson PJ,et al.,NeuroRx.,2006;3(1):22.,;,Drevets WC.,Curr Opin Neurobiol.,2001;11(2):240.,Blackburn-Munro G,Blackburn-Munro RE.,J Neuroendocrinol.,2001;13(12):1009.;,APA.,DSM-IV-TR,.2000:352.,微观到宏观的效应,抑郁症患者的,DLPFC,和,dACC,活性减弱,与对照者相比，静息时抑郁症患者活性增强,(,红色,),和减弱,(,蓝色,),的脑区,.,活性增强,:LOPFC,VMPFC,杏仁核,丘脑,尾状核,活性减弱,:DLPFC,岛叶,前膝部 和,dACC,颞上回,.,Fitzgerald PB,et al.,Hum Brain Mapp.,Epub ahead of print,MArmstrong User:,DLPFC=,背外侧前额叶皮质,LOPFC=,外侧眶前额