第四章 心境障碍1

Historicoverview•Hippocrates:•Kahlbaum(1882):“Cyclothymia”,“Dysthymia”•Kraepelin(1886):“manic-depressivedisorder”Definition•Mooddisordersareagroupofmentaldisorderscharacterizedbyobviousandpersistentelationordepressionofmood.•Themooddisturbanceiscommonlyassociatedwithcognitiveandbehavioralchanges.•Inseverecases,psychoticsymptoms,suchashallucinationanddelusion,maybeobserved.•Thereisatendencyforthedisorderstorecur,butmostrecurrentepisodeswilleventuallyremit.Incertaincases,anepisodemaybecomechronicandresidualsymptomsareobserved.定义•以显著而持久的情绪障碍为主要症状的精神障碍，以心境高扬或低落为基本临床相，伴有相应的思维和行为改变。有反复发作的倾向，间歇期大都精神活动正常。少数病例可有残留症状或转为慢性。classificationMoodDisordersWithorWithoutpsychiatricsymptomsManicepisode(mania)Depression(unipolar)SingleepisodeRecurrentepisodeBipolardisordersBipolar-Ⅰ(withmania)Bipolar-Ⅱ(withhypomania)MixedtypeRapid-cyclingbipolardisorderCyclothymiadisorderDysthymia为一大类疾病情感性障碍躁狂发作(症)抑郁症单次发作反复发作激越性迟钝性精神病性双相障碍双相I型双相II型混合相快速循环型环性心境障碍心境恶劣障碍(抑郁性神经症)1.Manicepisode（unipolar）•Thedisorderischaracterizedbyelatedandexpansivemoodthatisoutofkeepingwiththeindividual’scircumstances.•Themooddisturbancemayvaryfromcarefreejovialitytouncontrollableexcitement.Sometimes,irritabilityisthepredominantpresentation.•Inmildcases,impairmentofsocialfunctionmaybeabsentorminimal.Psychoticsymptoms,suchasdelusionsandhallucinations,maybeobservedinseverecases.2.MajorDepressiveepisode（unipolar）•characterizedbydepressedmoodthatisoutofkeepingwiththecircumstances.Itmayvaryfromlowmoodtomelancholia,orevenstupor.•Inseverecases,psychoticsymptoms,suchasdelusionsandhallucinations,maybepresent.•Anxietyandmotoragitationmaybemoreprominentthandepressioninsomecases.3.Biopolardisorders•BipolarIdisorder:•consistingofepisodesofmaniacyclingwithdepressiveepisodes.•Experiencesamajordepressiveepisodeandhashadoneormoremanicepisodic.3.Biopolardisorders•BipolarIIdisorder:•consistingofepisodesofhypomaniacyclingwithdepressiveepisodes•Experiencesamajordepressiveepisodeandhashadoneormorehypomanicepisodic3.BiopolardisordersRapidcyclingBipolardisorder•PatientswithRapidcyclingBipolardisorderexperiencefourormoreaffectiveepisodesperyear.4.Cyclothymicdisorder•consistingofcyclingepisodesofhypomaniaandlesssevereepisodesofdepression.5.Dysthymia•Consistsofadepressedmood,andatlesstwootherdepressivesymptoms.•Notofsufficientseveritytomeetthecriteriaformajordepression.•Notanymanicorhypomanicepisodic.6.OtherMoodDisorders•MooddisorderduetoageneralmedicalconditionAnalgesics(eg,indomethacin,opiates)Antibiotics(eg,ampicillin)Antihypertensiveagents(eg,propranolol,reserpine,α-methyldopa,clonidine)Antineoplasticagents(eg,cycloserine,vincristine,vinblastine)CimetidineL-Dopa•Substance-inducedmooddisorderAlcoholCocaineOpiatesEpidemiology人类前十位功能障碍性(disability)疾病:(CJLMurray等,1995)*①单相重性抑郁10.7%②缺铁性贫血4.7%③跌伤4.6%*④酒精滥用3.3%⑤慢阻肺3.1%*⑥双相情感障碍3.0%⑦先天性疾病2.9%⑧骨关节炎2.8%*⑨精神分裂症2.6%*⑩强迫症2.2%Prevalence（患病率）America•男性终身患病率4.8％•女性终身患病率9%•平均7%•双相障碍1.6%•恶劣心境3.3%•抑郁症13~20%Prevalence（患病率）影响因素•女性高于男性约为2~3:1•双相低于单相•国内报道低于国外•发病年龄：20－25岁病因和发病机制(一)遗传研究临床表现—家系调查－寄养子研究－双生子研究－遗传模式分析－连锁分析－候选基因－基因组扫描遗传研究家系调查：（1924-1954）躁郁症亲属患病率父母：３.２％～２３.４％，平均１４.６％兄弟、姐妹：２.７％～23％，平均１０.９％遗传研究Gorshon（1982）：单相、双相患者一级亲属患病率为15－20％双相家属抑郁症患病率１４.２％抑郁症家属抑郁症患病率１６.６％为对照组３倍多心境障碍的单卵双生与双卵双生的同病率单卵双生双卵双生references同病的双生子对数/总双生子对数同病率(%)同病的双生子对数/总双生子对数同病率(%)Luxenberger(1930)3/475.00/130.0Rosanoffetal(1935)16/2369.611/6716.4Slater(1953)4/757.14/1723.5Kallman(1954)25/2792.615/5523.6HarvaldandHauge(1965)10/1566.72/405.0Allenetal(1974)5/1533.30/340.0Bertelsen(1979)32/5558.30/5217.3总平均95/14665.039/27814.0数据未经年龄校正，诊断包括了双相和单相障碍遗传研究双生子研究总结(McGuffin)：双相障碍主要由遗传决定单相障碍可能主要源于遗传和环境的共同作用遗传研究寄养子研究：双相障碍生物学亲属中情感障碍患病率为31%对照组患病率为2%被收养和未被收养的双相障碍先证者的亲属患病率类似(26%)遗传研究寄养子研究总结：遗传因素而不是寄养关系，影响ＢＰ的家庭患病率分子遗传学研究双相障碍与18号染色体联锁21号染色体联锁与X染色体长臂末端连锁与5-HT受体基因多态性可能关联研究结果不一致——疾病的遗传异质性遗传研究家系研究小结：1.在情感障碍家系中，发生疾病的机率远较一般人口高；血缘关系越近，发病机率越高2.双生子和寄养子研究显示,遗传因素与发病有密切关系3.双相遗传倾向似较单相型明显.4.遗传传递方式不明5.分子遗传研究结果不一致，难以定论(二)生化机理去甲肾上腺素（Norepinephrine,NE)抑郁症尿MHPG（3-甲氧-4-苯酚糖，NE的中枢代谢产物）减少抗抑郁剂使NE受体敏感性降低电休克使NE受体敏感性降低抗抑郁剂使受体介导作用延迟NE受体敏感性增高→抑郁5-羟色胺（Serotonin,5-HT)抑郁症血浆色氨酸水平降低抑郁症CSF中5-HIAA降低三环类、SSRI类抑制5-HT重摄取发挥抗抑郁作用胆碱能、多巴胺能和GABA能系统1.胆碱能假说：抑郁症存在过度的胆碱能活动2.多巴胺能活动抑制脑脊液HVA浓度降低L-多巴及DA受体激动剂有一定抗抑郁作用3.GABA系统作用：抗抑郁药影响GABA受体抗癫痫药卡巴西平等影响GABA含量的调控，对抑郁起作用抑郁症发病的主要生化机理总结中枢ＮＥ和/或５－ＨＴ功能不足突触前受体（α2肾上腺素受体）数目增多或受体敏感性增加（ＮＥ释放减少或功能下降）（三）神经内分泌研究1.内分泌疾病如甲状腺功能低下，柯兴氏综合征等有明显抑郁症状2.ＤＳＴ：下丘脑－垂体－肾上腺轴（HPA）功能障碍半数患者皮质醇分泌增加对地塞米松（dexamethasone）不产生抑制反应(DST阳性)3.ＴＲＨ：下丘脑－垂体－甲状腺轴（HPT）功能障碍15%的患者甲状腺自身抗体增高抗抑郁药+T3对部分难治性患者有效(四)器质性因素MRI：额叶和颞叶皮质散在高密度影像增多fMRI：左额叶和左颞叶局部血流低灌注PET：左扣带回前部和额叶背外侧有血流量减少(五)心理社会因素负性的认知方式（Negativecognitivestyle）•Beck’scognitivetheory(AaronBeck,1967)•Oneofthemostinfluentialtheoriesofdepression•NegativecognitionsarecentraltodepressionEarlyexperienceDepressionFormationofdysfunctionalbeliefsCriticalincidentsBeliefsactivatedNegativeautomaticthoughtssymptomsofdepressionBehavioralMotivationalAffectivecognitiveSomaticNegativecognitivetriad(抑郁症的认知三联征)：Negativethoughtabouttheself(负性的自我反省):“Iamugly”“Iamworthless”“Iamfailure”Negativethoughtaboutone’sexperienceandthesurroundingworl