人体结构与功能 23-Schizophrenia学习资料

SCHIZOPHRENIA

Zhang,Bin

InstituteofPharmacology

SchoolofMedicine

ShandongUniversity

神经病：指神经系统发生的器质性疾病，一般都有神经组织结构的改变。主要表现是神经功能损害，如意识障碍、失语、瘫痪、抽搐、震颤、麻木、疼痛、大小便障碍、动作不稳、感觉减退或消失等。精神病：是大脑高级神经活动严重障碍的疾病，常表现为认知、情感、意志和行为的反常。有两大类：功能性精神病及器质性精神病。Prevalence:1%SlightlyincreasedprevalenceinurbanareasNoobviousdifferencebetweensexesNoinfluenceofculture,ethnicbackgroundTheaverageageofonsetisearlierinmenWHO10月10日--世界精神卫生日病例

Jane，22岁，两年前开始变得不合群,迷恋宗教,并说自己肩负着拯救国家的使命,有个internalvoices指导她。医生诊断其患有schizophrenia,开了neuroleptic。Jane的症状有所缓解，但感觉头晕乏力，体重也增加了，整个人怪怪的，未能规律服药，自觉mentallynumb,曾企图自杀，医生又给她添加了antidepressantdrug。一段时间后，Jane又来就诊，披头散发、衣着不整、不合时令、沉默少语、面无表情，并说internalvoices仍来光顾她。Thiscasegivesrisetothefollowingquestions:1.Whatistheexplanationforthesymptoms?Symptoms2.Whatmayhavecausedthisdisease?Aetiology3.Whataretheneurobiologicalmechanism?Neurobiology4.Isthispatientreceivingthemostappropriate?Treatment5.Whatisthelong-termprognosis?Symptoms

Formalthoughtdisorder(形式思维障碍)Emotionaldisorders(情感障碍)Motor,volitionalandbehaviouraldisorders(意志行为障碍)Abnormalperceptions(知觉异常)

Abnormalideas(思维内容障碍）Lackofinsight(自知力缺陷）Formalthoughtdisorder

(形式思维障碍)表现为思维联想过程缺乏连贯性和逻辑性

思维松弛思维破裂语词新作思维中断强制性思维Emotionaldisorders

(情感障碍)患者对周围事物情感反应缺失或不协调情感平淡情感淡漠情感与周围环境不协调Motor,volitionalandbehaviouraldisorders（意志行为障碍）孤僻离群、被动退缩、缺乏主动性，整日无所事事，生活懒散，意志减退，工作学习交往没有兴趣，能力明显下降，社会功能受损。还可出现愚蠢、幼稚、怪异行为。

刻板症(Stereotypy)装相(Mannerisms)紧张症(Catatonia)木僵症，蜡样屈曲(Catalepsy,

waxyflexibility)兴奋、冲动、行为杂乱（如破坏性行为、暴力、裸奔）Abnormalperceptions

(知觉异常)—hallucinations：指在客观现实中并不存在某种事物的情况下，患者却感知到他的存在。

幻听(Auditoryhallucinations)幻视(Visualhallucinations)幻嗅(Olfactoryhallucinations)幻味(Gustatoryhallucinations)Abnormalideas

（思维内容障碍）—delusion：是一种病理性的歪曲信念，这种信念与客观事实、所受教育水平、文化背景等不相符合，甚至荒谬离奇，但患者坚信不疑，无法被说服。

关系妄想(delusionsofreference)被害妄想(delusionsofpersecution)夸大妄想(grandiosedelusions)疑病妄想(hypochondriacaldelusions)妄想心境(delusionalmood)TypeⅠ(Positivesymptoms):

existenceofanabnormalphenomenondelusion,hallucination,thoughtdisorder,bizarrebehaviour,catatonia,etc.TypeⅡ(Negativesymptoms):

absenceordiminutionofnormalfunctionandreactions.

affective

apathy,socialwithdrawal,

poorinitiativeandmotivation,etc.ClassificationofschizophreniaAcuteepisodesChronicschizophreniaClinicalsubtypesofschizophrenia1.偏执型(妄想型):最常见，起病较慢，疗效较好2.青春型:较常见，起病快，疗效较好3.单纯型:较少见，起病较慢，疗效差4.紧张型:少见，起病快，疗效好5.末定型:6.其它:AetiologyGeneticaspects:

correlatedwiththedegreeofgeneticrelatednessSomato-biologicalfactors:

afterviralepidemicswintermonthsobstetriccomplicationsSocialenviromentfactors:

“schizophrenogenicmother”badlifeeventseconomicstatuscharacterNeurobiologyPathomorphologyresearchBiochemistrymetabolismresearch

Themolecularbasisforschizophreniaconcernswiththeabnormalitiesofsomeneurotransmitterfunction,especiallydopamine.NeurotransmittersofschizophreniaDopamine(DA)5-hydroxytryptamine(5-HT)Glutamate(Glu)

-aminobutyricacid(GABA)DopaminetheoryMostantipsychoticdrugsstronglyblockpostsynapticD2receptorsinthemesolimbic-mesocorticalsystemDrugsthatincreasedopaminergicactivity,suchaslevodopa,amphetamines,eitheraggravateschizophreniaorproducepsychosisinsomepatientsDopaminereceptordensityhasbeenfound,postmortem,tobeincreasedinthebrainsofschizophremicswhohavenotbeentreatedwithantipsychoticdrugsDopaminetheory

Mesocortical(中脑-皮层)DAsystemandMesolimbic(中脑-边缘)DAsystemactivity↑1.Nigrosubstantia-striatalDAsystem:

Regulateextrapyramidalfunction2.MesocorticalDAsystem3.MesolimbicDAsystem

Regulatecognition,thinking,emotion,feeling4.Tubero-infundibularDAsystem

RegulatepituitaryhormonereleaseTheSubtypesofDAReceptorD1，D2，D3，D4，D5subtypesDAreceptorclassifiedD1-likereceptors:D1andD5

D2-likereceptors:D2,D3,D4Nigro-striatalsystem：

D1-likereceptorsD2-likereceptors(D2、D3)Mesocorticalandmesolimbicsystem:D2-likereceptors(D2、D3、D4)Tubero-infundibularD2-likereceptors(D2)AntipsychoticdrugsPsychosocialinterventioninsulinshocktherapy,electricshocktherapyTreatmentAntipsychoticagents

(Neuroleptics)

(Majortranquilizers)TheMechanisms

ofAntipsychoticDrugs1.BlockD2–likereceptorinthemesolimbicandmesocorticalpathwaysofbrain.2.Block5-HTreceptors

Typicalantipsychotics

Phenothiazines(吩噻嗪类):

chlorpromazine,fluphenazine,trifluoperazine

Thioxanthenes(硫杂蒽类):flupenthixol

Butyrophenones(丁酰苯类):haloperidol

Atypicalantipsychoticssulpiride,amisulpride,clozapine,olanzapine,risperidone,seroquelClassification

ofAntipsychoticDrugs

Chlorpromazine

（氯丙嗪，wintermine,冬眠灵）In1952,chlorpromazinewasusedtotreatschizophreniaPharmacologicalEffectsBlockingDA-RCentralnervoussystemBlockingα-RandM-R

AutonomicnervoussystemBlockingDA-REndocrinesystemCentralnervoussystemAntipsychoticeffectsExtrapyramidalreactionsAntiemeticeffectsEffectsoftemperatureregulation(1)Antipsychoticeffect(neurolepticeffect):a.

Sedation：inducetosleepinnormalperson.

easytowake,noanesthesia,toleranceb.Antipsychoticeffectinschizophreniapatients.

notolerance

Mechanism:BlockD2likereceptorinmesolimbicandmesocorticalpathways.

(2)AntiemeticactionLowdoseblocksD2receptorofCTZLargedoseinhibitthevomitingcenterdirectlyNoeffectonvomitingcausedbyvestibularstimulusItiseffectiveinstubbornhiccup

(3)Effectontemperatureregulation

a.Thetemperaturechangeddependentwithenvironmenttemperature.(poikilothermia,变温)b.Hypothermiaisnotonlyinfeverpatients,butalsoinnormalindividuals.Mechanisms:inhibittemperature-regulatingcenterinhypothalamus.(4)ExtrapyramidalreactionExtrapyramidalreactionsoccurringearlyduringtreatmentwithchlorpromazineincludeParkinson'ssyndrome,akathisia,acutedystonicreactions.TardivedyskinesiaisalateoccurringsyndromeAutonomicnervoussystem(1)Blockingα-RvesseldilationPeripheralresistance↓OrthostatichypotensionHeartrate↑NotsuitableforthetreatmentofhypertensionAutonomicnervoussystem(2)BlockingM-RParalysisofaccommodationDrymouthDifficultyurinatingConstipationUroschesisParalyticileus尿潴留

麻痹性肠梗阻EndocrinesystemProlactinrelease-inhibitingfactor(PIF)↓PRL↑Amenorrhea-galactorrheaInfertilityGonadotropin-releasehormone(GnRH)↓FSH,LH↓DelayedovulationCorticotropin(ACTH)↓GSH↓Growthhormone(GH)↓treatGiantism催乳素乳腺肿大、泌乳FSH、LH延迟排卵催乳素抑制因子促性腺激素生长激素糖皮质激素抑制对内分泌系统的作用促肾上腺皮质激素治疗巨人症ClinicalApplicationSchizophreniaVomiting＆IntractablehiccupsHypothermiaanesthesia＆ArtificialhibernationSchizophreniaSchizophreniaistheprimaryindicationofchlorpromazine.(Ⅰtype,acute)Themanicepisodeinbipolaraffectivedisorderoftenrequirestreatmentwithchlorpromazine.Chlorpromazineiseffectiveindysphoria,hallucination,delusioncausedbyotherpsychoses.VomitingandIntractablehiccupsVomitingcausedbydrugsanddiseases.Chlorpromazinehasamarkedcurativeeffectinintractablehiccups.Noeffectonvomitingcausedbymotionsicknessintractablehiccups:Aspasmofthediaphragmthatcausesasuddeninhalationfollowedbyrapidclosureoftheglottiswhichproducesasound.chlorpromazinedeepsleepLyticcocktail

dolantintemperature↓

promethazinebasalmetabolism↓tolerance↑

Artificialhibernationreaction↓seriousinjuryIndicationhyperpyrexiashockhyperthyroidismcrisis…

Hypothermiaanesthesiaand

Artificialhibernation42

WhatisthedifferencebetweenNSAIDsandchlorpromazineinbodytemperatureregulation?Question43比较NSAIDs与氯丙嗪对体温的影响

NSAIDs氯丙嗪

机制抑制COX,抑制下丘脑体温减少PGs生成调节中枢作用特点降低高热体温，使体温随环境温不降低正常体温度变化应用炎性发热人工冬眠44

Comparisonbetween

NSAIDsandChlorpromazine

NSAIDsChlorpromazineMechanism

inhibitCOXin

inhibit

thermoregulatorCNS→

PGs↓makeitoutoffunction

Effect

setpoint

↓BTalterswiththeBT↓environmentaltemperatureClinicalusesfeverartificialhibernation

rheumaticfeverAdversereactions1.Commonadversereactions

(1)Excessivesedation(2)M-RBlockade(3)α-RBlockade2.Extrapyramidalreactions

(1)Parkinson’ssyndrome(2)Akathisia(3)Acutedystonia:Reason:blockDAreceptorsinthenigrostriatumTreatment:

(4)Tardivedyskinesia:

suckingandlickingofthelips(吸吮、舔舌、咀嚼三联征),abnormalchoreoathetoidmovements(舞蹈手足徐动症)Reason:

cholinergicdeficiencysecondarytosupersensitivityofDA-R(DAreceptorUp-regulation,presynapticDArelease)Treatment:Clozapine,olanzapine,risperidoneandseroquel3.Convulsionandepilepsy4.Psychosis5.Neurolepticmalignantsyndrome

6.Endocrinesystem7.Others:

hepatotoxicity:obstructivejaundicehaematologicaleffects:agranulocytosiscutaneouseffects:

pigmentationandphotosensitivityweightincrease镇静抗幻觉妄想锥体外系对阴性症状降压急性慢性氯丙嗪+++++++-+++

-氟奋乃静三氟拉嗪-+++++++++

奋乃静++++++-+

-氟哌啶醇-++++++++

Clozapine(氯氮平)atypicalantipsychoticagent