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单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,*,*,抑郁症的影像遗传学研究浅谈,抑郁症的影像遗传学研究浅谈,1,抑郁症影像遗传学研究浅谈-课件,2,1.抑郁症概念,2.抑郁症病因探究,3.抑郁症的影像遗传学研究,4.小结,1.抑郁症概念,3,抑郁症,心灵杀手,一种常见的心境障碍,典型症状:,情绪低落,思维迟缓,意志活动减退,认知障碍,全球抑郁症患者:3.5亿,WHO预计:2020年,人类第二大疾患,(13),Suicide,抑郁症心灵杀手一种常见的心境障碍,典型症状:Suicid,4,为什么会得抑郁症?,生物,神经,行为,环境,影像,心理,遗传,Mattay,et al,Biol Psychol 2019,为什么会得抑郁症?生物神经行为环境影像心理遗传Mattay,5,研究局限性,遗传学研究:,人格问卷,临床评估,神经电生理测验,(7),关联性背后的机制?,Mattay,et al,Biol Psychol 2019,研究局限性遗传学研究:Mattay et al Biol P,6,影像学研究:,海马(认知记忆),杏仁核(负性信息调节),扣带回前部(情感整合),前额叶皮层(信息加工),(8,11,),受试者的遗传背景?,研究局限性,影像学研究:研究局限性,7,影像遗传学,神经科学,遗传学,信息,/,工程学科,影像学,放射科医生,精神神经科医生,计算机图像处理专家,遗传学专家,统计学专家,新思路,影像遗传学,Mattay,et al,Biol Psychol 2019,影像遗传学神经科学遗传学信息/工程学科影像学放射科医生新思路,8,抑郁症影像遗传学的主要发现,5-HT相关的基因(色氨酸羟化酶(TPH)基因、5-HT,T,基因、5-HTTLPR、5-HT受体基因和单胺氧化酶基因等),儿茶酚氧位甲基转移酶(COMT)基因,脑源性神经营养因子(BDNF)基因,精神分裂症断裂-l型(DISC1)基因,载脂蛋白E(APOE)基因,大麻素受体1(CNRl)基因,(7),抑郁症影像遗传学的主要发现5-HT相关的基因(色氨酸羟化酶(,9,抑郁症影像遗传学的主要发现,(Frodl,,,et,al,.Acta Psychiatry,2019),5-HTTLPR,5-HTTLPR,抑郁症影像遗传学的主要发现(Frodl,et,al.Act,10,5-羟色胺转运基因启动序列,5-HT:生理和行为的调控因子,5-HTT:重摄取突触间隙的5-HT,5-HTTLPR:短等位基因(S),长等位基因(L),5-HT 5-HTT,5-HTTLPR,5-羟色胺转运基因启动序列5-HT:生理和行为的调控因子,11,(1)结构影像:,Hickie等,:,携带S等位基因-尾状核、扣带回、杏仁核体积减小,(1214),Frodl等,:,纯合L等位基因-灰质体积明显减小如背侧额前叶皮质、前扣带回皮质、杏仁核、海马前部等,(15),Taylor等:海马体积减小,早发(发病年 龄55岁)-S等位基因,抑郁症晚期发作的年龄-L等位基因,(12),(1)结构影像:,12,Hariri,(16),Heinz,(17),等:,负性刺激 S等位基因携带者杏仁核的活性更高,杏仁核与腹内侧前额皮质联系增强,5-HTTLPR基因多态性可能是情绪障碍的典型易患因素,.,Hariri,et al,.Science,2019,(,2,),功能,影像:,Hariri,et al.Science,2019(2,13,选择性5-羟色胺再摄取抑制剂(SSRIs):药物对5-HTT的占有率在 LL等位基因携带者中较高,从而对抗抑郁剂治疗反应较好,(18),抑郁症个体化治疗提供依据,(,2,),药物治疗反应,:,抑郁症个体化治疗提供依据(2)药物治疗反应:,14,小结 1,现状:,抑郁症严重危害人类的身心健康,3.5亿患者只是冰山一角;,抑郁症的影像遗传学研究尚处于初步阶段;,抑郁症发病与大脑改变的因果关系;,候选基因选择,研究结论各异。,小结 1现状:,15,展望:,多学科密切合作,前瞻性的随访研究,?,单个候选基因,多基因,全基因组并联分析(GWAS),高危险个体识别,个体化治疗,小结,2,展望:小结 2,16,1.Nestler EJ,M Barrot,RJ DiLeone,et al,.,Neurobiology of depression,.Neuron,2019,34(1):13-25.,2.Belmaer R H,Agam G.,Major depressive disorderJ,.,N Engl J Med,2019,358:55-68.,3.顾牛范.,抑郁症全科医生诊疗中的误区J.,中国新药与临床杂志,2019,24(8);592-584.,4.Goodman M,New AS,Triebwasser J,et,al.Phenotype,endophenotype,and genotype comparisons,between borderline personality disorder and major depressive disorderJ.,J Pers Disord,2019,24:38-59,5.Tairyan K,Illes J.,Imaging genetics and the power of combined technologies:a perspective from neuroethicsJ.,Neuroscience,2009,164(1):7-15,.,6.卢恬,屠洁,王立平.,抑郁症的发病机制研究进展,,先进技术研究通报,2009,3(1),7.Douglas F,Levinso.,The Genetics of depression:a review,.Biol Psychiat,2019,60(2):84-92,8.Andres M.,Is major depression a neurologic disorder with psychiatric symptoms,.Epilepsy,Behavior,2019,5:634-644,.,9.Frodl T,Schaub A,Banac S,et al,.,Reduced hippocampal volume correlates with executive dys,-,functioning in major depression,J,.,Psychiatry Neurosci.2019,31:316-323,.,10.Greicius,Flores,Menon,et al,.,Resting-state functional connectivity in major depression:,abnormally increased contributions from subgenual cingulate cortex and thalamusJ.,Biol Psy-,chiatry,2019,62:429-437,.,11.Amit Anand,Yu Li,Yang Wang,et al,.,Activity and connectivity of brain mood regulating circuit,in depression:a functional magnetic resonance studyJ.,Biol Psychiatry,2019,57:1079-1088,.,参考文献,1.Nestler EJ,M Barrot,RJ DiL,17,12.Taylor WD,Steffens DC,Payne ME,et,al,.,Influence of serotonin transporter promoter region polymorphisms on hippocampal volumes in late-life depression,.Arch Gen Psychiatry,2019,62:537-544.,13.Hickie IB,Naismith SL,Ward PB,et al,.,Serotonin transporter gene status predicts caudate nucleus but not amygdale or hippocampal volumes in older persons with major drepression,J,.,Affect Disord,2019,98:137-142.,14.Pezawas L,Meyer-Lindenberg A,Drebant EM,et al.5-HTTLPR polymorphism impacts human cingulated-amygdala interactions:a genetic susceptibility mechanism for depression,.,Nat Neuro-sci,2019,8:328-334.,15.Frodl T,Koutsouleris N,Bottlender R,et al,.,Reduced gray matter brain volumes are associated with variants of the serotonin transporter gene in major depression,J,.,Affec Disord,2019,98:137-142.,16.Hariri AR,Drabant EM,Munoz KE,et al,.,A susceptibility gene for affective disorders and the response of the human,amydala,.Arch Gen Psychiatry,2019,62:146-152.,17.Heinz A,Braus DF,Smolka MN,et al,.,Amygdala-perfrontal coupling depends on a genetic variation of the serotonin transporter.,Nat Neurosci,2019,8:20-21.,18.Ruh HG,Ooteman W,et al,.,Serotonin transporter gene promoter polymorphisms modify the association between paroxetine serotonin transporter occupancy and clinical response in major depressive disorder,J,.,Pharmacogenet Genomics,2009,19:67-76.,19.罗松,张龙江,卢光明,基于功能MRI的影像遗传学研究进展,,中华放射学杂志,2019,48(1),20.Mattay VS,Goldberg TE,Sambataro F,et al,.,Neurobiology of cognitive aging:insights from imaging genetics,.Biol Psychol,2019,79(1):9-22.,参考文献,12.Taylor WD,Steffens DC,Pay,18,抑郁症影像遗传学研究浅谈-课件,19,抑郁症影像遗传学研究浅谈-课件,20,抑郁症影像遗传学研究浅谈-课件,21,抑郁症影像遗传学研究浅谈-课件,22,
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