抑郁癥影像遺傳學(xué)研究淺談-課件

1、抑郁癥的影像遺傳學(xué)研究淺談抑郁癥的影像遺傳學(xué)研究淺談抑郁癥影像遺傳學(xué)研究淺談-課件1.抑郁癥概念2.抑郁癥病因探究3.抑郁癥的影像遺傳學(xué)研究4.小結(jié)1.抑郁癥概念抑郁癥心靈殺手一種常見的心境障礙，典型癥狀：情緒低落 思維遲緩 意志活動(dòng)減退認(rèn)知障礙全球抑郁癥患者：3.5億WHO預(yù)計(jì)：2020年，人類第二大疾患(13)Suicide抑郁癥心靈殺手一種常見的心境障礙，典型癥狀：Suicid為什么會(huì)得抑郁癥？生物神經(jīng)行為環(huán)境影像心理遺傳Mattay et al Biol Psychol 2019為什么會(huì)得抑郁癥？生物神經(jīng)行為環(huán)境影像心理遺傳Mattay 研究局限性遺傳學(xué)研究:人格問卷臨床評(píng)估神經(jīng)電生理

2、測(cè)驗(yàn)(7)關(guān)聯(lián)性背后的機(jī)制？Mattay et al Biol Psychol 2019研究局限性遺傳學(xué)研究:Mattay et al Biol P影像學(xué)研究：海馬（認(rèn)知記憶）杏仁核（負(fù)性信息調(diào)節(jié)）扣帶回前部（情感整合）前額葉皮層（信息加工）（811）受試者的遺傳背景？研究局限性影像學(xué)研究：研究局限性影像遺傳學(xué)神經(jīng)科學(xué)遺傳學(xué)信息/工程學(xué)科影像學(xué)放射科醫(yī)生精神神經(jīng)科醫(yī)生計(jì)算機(jī)圖像處理專家遺傳學(xué)專家統(tǒng)計(jì)學(xué)專家新思路影像遺傳學(xué)Mattay et al Biol Psychol 2019影像遺傳學(xué)神經(jīng)科學(xué)遺傳學(xué)信息/工程學(xué)科影像學(xué)放射科醫(yī)生新思路抑郁癥影像遺傳學(xué)的主要發(fā)現(xiàn)5-HT相關(guān)的基因（色氨酸羥化

3、酶(TPH)基因、5-HTT基因、5-HTTLPR 、5-HT受體基因和單胺氧化酶基因等）兒茶酚氧位甲基轉(zhuǎn)移酶（COMT）基因腦源性神經(jīng)營養(yǎng)因子(BDNF)基因精神分裂癥斷裂-l型(DISC1)基因載脂蛋白E（APOE）基因大麻素受體1(CNRl)基因 （7）抑郁癥影像遺傳學(xué)的主要發(fā)現(xiàn)5-HT相關(guān)的基因（色氨酸羥化酶(抑郁癥影像遺傳學(xué)的主要發(fā)現(xiàn)(Frodl，et,al. Acta Psychiatry,2019)5-HTTLPR5-HTTLPR抑郁癥影像遺傳學(xué)的主要發(fā)現(xiàn)(Frodl，et,al. Act5-羥色胺轉(zhuǎn)運(yùn)基因啟動(dòng)序列5-HT：生理和行為的調(diào)控因子5-HTT：重?cái)z取突觸間隙的5-HT

4、5-HTTLPR ：短等位基因(S)，長等位基因(L) 5-HT 5-HTT 5-HTTLPR5-羥色胺轉(zhuǎn)運(yùn)基因啟動(dòng)序列5-HT：生理和行為的調(diào)控因子（1）結(jié)構(gòu)影像： Hickie等: 攜帶S等位基因-尾狀核、扣帶回、 杏仁核體積減小(1214)Frodl等: 純合L等位基因-灰質(zhì)體積明顯減小如背側(cè)額前葉皮質(zhì)、前扣帶回皮質(zhì)、杏仁核、海馬前部等(15) Taylor等: 海馬體積減小 早發(fā) (發(fā)病年 齡55歲) -S等位基因 抑郁癥晚期發(fā)作的年齡-L等位基因(12)（1）結(jié)構(gòu)影像：Hariri(16), Heinz(17) 等: 負(fù)性刺激 S等位基因攜帶者杏仁核的活性更高,杏仁核與腹內(nèi)側(cè)前額皮質(zhì)

5、聯(lián)系增強(qiáng)5-HTTLPR基因多態(tài)性可能是情緒障礙的典型易患因素 . Hariri, et al. Science, 2019（2）功能影像：Hariri, et al. Science, 2019（2選擇性5-羥色胺再攝取抑制劑(SSRIs) ：藥物對(duì)5-HTT的占有率在 LL等位基因攜帶者中較高，從而對(duì)抗抑郁劑治療反應(yīng)較好（18） 抑郁癥個(gè)體化治療提供依據(jù)（2）藥物治療反應(yīng)：抑郁癥個(gè)體化治療提供依據(jù)（2）藥物治療反應(yīng)：小結(jié) 1現(xiàn)狀：抑郁癥嚴(yán)重危害人類的身心健康，3.5億患者只是冰山一角；抑郁癥的影像遺傳學(xué)研究尚處于初步階段；抑郁癥發(fā)病與大腦改變的因果關(guān)系；候選基因選擇，研究結(jié)論各異。小結(jié) 1

6、現(xiàn)狀：展望：多學(xué)科密切合作前瞻性的隨訪研究?單個(gè)候選基因多基因全基因組并聯(lián)分析（GWAS）高危險(xiǎn)個(gè)體識(shí)別個(gè)體化治療小結(jié) 2展望：小結(jié) 21.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.顧牛范.抑郁癥全科醫(yī)生診療中的誤區(qū)J.中國新藥與臨床雜志,2019,24(8);592-584.4.Good

7、man 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: 38-595.Tairyan K, Illes J. Imaging genetics and the power of combined technologies: a perspective from neuroethicsJ.

8、 Neuroscience, 2009, 164(1):7-15.6.盧恬，屠潔，王立平.抑郁癥的發(fā)病機(jī)制研究進(jìn)展，先進(jìn)技術(shù)研究通報(bào)，2009，3（1）7.Douglas F, Levinso. The Genetics of depression: a review. Biol Psychiat, 2019, 60(2):84-928.Andres M. Is major depression a neurologic disorder with psychiatric symptoms. Epilepsy Behavior, 2019, 5:634-644.9.Frodl T, Schau

9、b A, Banac S, et al. Reduced hippocampal volume correlates with executive dys- functioning in major depressionJ. Psychiatry Neurosci.2019,31:316-323.10.Greicius, Flores, Menon, et al. Resting-state functional connectivity in major depression: abnormally increased contributions from subgenual cingula

10、te 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, 57:1079-1088.參考文獻(xiàn)1.Nestler EJ, M Barrot, RJ DiL12.Taylor WD, S

11、teffens 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

12、or hippocampal volumes in older persons with major drepressionJ .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

13、.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 depressionJ .Affec Disord, 2019, 98:137-142.16.Hariri AR, Drabant EM, Munoz KE, et al. A susceptibility gene for affective disorders and the res

14、ponse 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.羅松，張龍江，盧光明基于功能MRI的影像遺傳學(xué)研究進(jìn)展，中華放射學(xué)雜志，2019，48 （1）20. Mat