schizophrenia,depression and anxiety 精神分裂,焦虑和抑郁

Chapter17，19，20

Schizophrenia,AnxietyandDepressionSchizophrenia,AnxietyandDepressionPsychologicalDisordersMentalDisordersPsychologicalDisordersSchizophrenia,AnxietyandDepressionPsychologicalDisordersMentalDisorders(PsychologicalDisorders)Disturbanceofthought,mood,perceptionAdiagnosisofamentaldisordershouldbereservedforpeoplewithproblemsthatseriouslyinterferewiththeirlivesAffectsaperson’sbehaviorinvoluntarily,causingbizarreand/orinappropriatebehavior.MentalDisordersandPhysicalDisordersMentaldisorderseemsdifferentfrom

physicaldisordersbecausethepersonoftenlooksthesame.Whatchangesisthewaythepersonthinks,feelsandbehaves.WhatcausesMentalDisorders?CausesofMentalDisordersCausesofMentalDisorders?Features?MentalDisordertendstobe

‘Episodic’Whensomeonehasamentaldisorderitdoesn’tmeantheyaredisturbedallofthetime.Mostpeoplehaverelativelyshort,‘acute’episodesofdisorder.

Therestofthetimetheycanfunctionatanindividuallypredictablelevel.

CausesofMentalDisorders?FeaturesTypes?TypesMentaldisordersThereisawidevarietyofpsychologicaldisorders.Classifyingthemisaprerequisitetodiagnosisandtreatment.CognitiveDisordersPsychoticDisordersAffectiveDisordersAnxietyDisordersOtherDisordersDeliriumDementiaAmnesicSchizo-phreniaSchizo-affectiveDelusionalPsychoticMajorDepressionDysthymiaBipolarIBipolarIICyclothymiaPanicAgarophobiaPhobiasOCDPTSDAcuteStressGeneralizedAnxietyD/OsSubstancerelatedSomatoformFactitiousDissociativeSexualEatingSleepImpulseAdjustmentD/OsTypesMentaldisordersCognitiveDisordersPsychoticDisordersAffectiveDisordersAnxietyDisordersOtherDisordersDeliriumDementiaAmnesicSchizo-phreniaSchizo-affectiveDelusionalPsychoticMajorDepressionDysthymiaBipolarIBipolarIICyclothymiaPanicAgarophobiaPhobiasOCDPTSDAcuteStressGeneralizedAnxietyD/OsSubstancerelatedSomatoformFactitiousDissociativeSexualEatingSleepImpulseAdjustmentD/OsTypesMentaldisordersCauses,FeaturesTypes?Mechanism?MentalDisordersCauses,MentalDisordersMechanism?Structure,FunctionsandDisordersBrainSchizophreniaAnxietyDepressionPrefrontalcortexSchizophreniaSchizophreniaSchizophreniaisachronic,severebraindisease.Peoplewithschizophreniaoftensufferterrifyingsymptomssuchashearinginternalvoicesnotheardbyothers,orbelievingthatotherpeoplearereadingtheirminds,controllingtheirthoughts,orplottingtoharmthem.Thesesymptomsmayleavethemfearfulandwithdrawn.Theirspeechandbehaviorcanbesodisorganizedthattheymaybeincomprehensibleorfrighteningtoothers.Schizophrenia1、Positivesymptoms

Symptomssuchashearinginternalvoicesnotheardbyothers,orbelievingthatotherpeoplearereadingtheirminds,controllingtheirthoughts,orplottingtoharmthem.2、Negativesymptoms

Thesesymptomsmayleavethemfearfulandwithdrawn.

3、Disorganizedsymptoms

Theirspeechandbehaviorcanbesodisorganizedthattheymaybeincomprehensibleorfrighteningtoothers.SymptomsPositivesymptomsHallucinations:Sensoryexperiencesintheabsenceofexternalstimulation.Delusions:Falsebeliefsaboutrealitythathavenobasisinfact.(Excess)“Ihearvoicestellingmetodoevilthings.”“Mydoctorremovedallmyinternalorgansandreplacedthemwithsomebodyelse’s.”Negativesymptoms(Deficit)Weaksocialinteractions(Socialwithdrawal）LittleemotionalexpressionorspeechLossofmotivationandinterestWorkingmemorydeficitsThesetendtobestableovertime,hardtotreat.SchizophreniaSymptoms+Perception:Hallucinations+Cognition:Delusions+Emotion:Bluntedaffectandsocialwithdrawal+Behaviour:BizarrebehaviourSchizophrenia-disturbancesofthought,emotions,andbehavior.Ofallthementaldisorders,schizophreniaisthemostbizarreandprobablythemostpuzzling.bygeneticsbyavirusbyachemicalbybirthdamagebystressWhatCausesSchizophrenia?(Etiology)Despiteyearsofresearchthereisnoconsensusonasingleetiologyforthisdisorder.ItappearsthatschizophreniacouldbecausedbyKH2F090509_05BrainstructuresandfunctionBrainchemistryWhatOccursintheBrainofSomeonewithSchizophrenia?StructuralandfunctionalchangesinbrainSchizophrenia

Decreasedsizeof:cerebralcortex,thalamus,temporal

lobesandhippocampus

Enlargementofbasalganglia

Enlargedventricles(reflectinglossofbraincells)

ReducedmetabolicactivitywithinprefrontalcortexNeuroimagingDisorderedneuronsinhippocampusReducedmetabolicactivitywithinprefrontalcortexNeurochemicalchanges

inbrainSchizophreniaLevelsofneurotransmittersAbnormalNeurotransmitter“imbalances”maytriggersymptomsofschizophrenia.DopamineSerotoninGlutamateNeurochemicalchanges

inbrainSchizophreniaLevelsofneurotransmittersAbnormalNeurotransmitter“imbalances”maytriggersymptomsofschizophrenia.DopamineSerotoninGlutamateSchizophreniaToomuchdopamineDopamineabnormalitiesSchizophreniaDopamineabnormalitiesToomuchdopamineDopamineantagonistscanbeusedtotreatschizophrenia.OriginaltheoryproposedthatanoveractivationofDAledtoschizophrenicsymptoms.Drugs,suchasamphetamines,thatreleaseDAatsynapsescancauseshizophrenicsymptomsinpeoplewhodonothaveschizophrenia.Abreakthroughintherapy:Reserpine,depletingdopamineinthebrain,wasusedtotreatschizophrenia.Chlorpromazine,aDAantagonist,wasusedtoalleviatethesymptomsofschizophrenia.ProlongeduseofthesedrugsproducedParkinson’slikesymptoms.Abreakthroughintheory:DopaminehypothesisofschizophreniaThepsychoticsymptomsofschizophreniaarerelatedtodopaminergichyperactivityinthebrain.HyperactivityofdopaminergicsystemsduringschizophreniaisresultoftheincreaseddopamineandtheincreasedsensitivitydopamineD2receptors.Abreakthroughintheory:DopaminehypothesisofschizophreniaSchizophreniaDopamineabnormalitiesToomuchdopaminedoesnotcauseallsymptomsofschizophreniaAmphetaminesdonotworsenallpatientsSomeactuallygetbetter:Positivesymptomsworsen,butnegativesymptomsgetbetterAntipsychoticsonlyamelioratesomesymptomsMorerecentlyithasbeenhypothesizedthatDopamineabnormalitiesPositivesymptomsarecausedbyanoveractivationofspecificDApathwaysNegativesymptomsarisefromandunderactivationofdifferentDApathwaysDifferindifferentDApathwaysSchizophreniaIndifferentDApathwaysThenigrostriatalsystemrunsfromthesubstantianigra(A9)forwardstothestriatum.Themesolimbicocorticalsystemrunfromtheventraltegmentalarea(A10)forwardstothenucleusaccumbensandfrontalcortex.AbnormalDAactivitiesinthemesolimbicocorticalhasbeenimplicatedinschizophrenia.ThenigrostriatalsystemisdamagedinParkinson'sdisease.DopamineabnormalitiesDopamineabnormalitiesInthemesolimbicocorticalsystemSchizophreniaNucleusaccumbensVentraltegmentumPrefrontalcortexUnderactivityofdopamineneuronsinthemesocorticalpathwayintheprefrontalcortexthatmaycausenegativesymptomsOveractivityofdopamineneuronsinthemesolimbicpathwaythatmaycausepositivesymptoms.DopamineabnormalitiesInthemesolimbicocorticalsystemSchizophreniaNucleusaccumbensVentraltegmentumPrefrontalcortex-UnderactivityofdopamineneuronsinthemesocorticalpathwayintheprefrontalcortexthatmaycausenegativesymptomsDopamineabnormalitiesInthemesolimbicocorticalsystemSchizophreniaNucleusaccumbensVentraltegmentumPrefrontalcortexExcessivedopaminergictransmissioninthemesolimbicsystem=positivesymptomsDecreasedactivityinthemesocorticalconnectionsofprefrontalcortex=negativesymptomsUnderactivityofdopamineneuronsinthemesocorticalpathwayintheprefrontalcortexthatmaycausenegativesymptomsOveractivityofdopamineneuronsinthemesolimbicpathwaythatmaycausepositivesymptoms.NucleusaccumbensVentraltegmentumPrefrontalcortexNormalSchizophreniaPositivesymptomsNegativesymptomsDopamineabnormalitiesInthemesolimbicocorticalsystemSchizophreniaNucleusaccumbensVentraltegmentumPrefrontalcortexDopamineDA1receptors:DA1,D1BDA2receptors:D2,D3andD4AbnormalitiesNeurochemicalchanges

inbrainSchizophreniaLevelsofneurotransmittersAbnormalNeurotransmitter“imbalances”maytriggersymptomsofschizophrenia.DopamineSerotoninGlutamateSchizophreniaSerotoninInvolvement5-HTagonistscauseastatesimilartoschizophrenia.Abnormalities5-HTantagonistshaveatherapeuticefficacy.SchizophreniaSerotoninInvolvementAbnormalitiesNeurochemicalchanges

inbrainSchizophreniaLevelsofneurotransmittersAbnormalNeurotransmitter“imbalances”maytriggersymptomsofschizophrenia.DopamineSerotoninGlutamateSchizophreniaGlutamateabnormalityInsufficientglutamateTheglutamatefunctionsarehypoactiveinthebrainsofpeoplediagnosedwithschizophreniaandthisisthoughttocausethesymptomsassociatedwiththedisorder.SchizophreniaGlutamateabnormalityPhencyclidine(PCP):(GlutamateNMDAantagonist)AnestheticAuditoryhallucinationsDelusionsRelapseinpreviouslyrecoveredschizophrenicsInsufficientglutamateIfaglutamateANTAGONISTmimicsschizophrenia,whynotgiveaglutamateAGONISTastreatment?Seizures!!(alsoexcitotoxicity)SchizophreniaGlutamateabnormalityInsufficientglutamateWhichglutamatergicpathwaysinthebrainarehypoactiveinschizophrenia?Neurochemicalchanges

inbrainSchizophreniaLevelsofneurotransmittersAbnormalNeurotransmitter“imbalances”maytriggersymptomsofschizophrenia.DopamineSerotoninGlutamateThebrainofaschizophrenicmayproduceahallucinogen-likechemicalthatcausestheschizophrenia.SchizophreniaTherapiesAcombinationofinterventionsarerequiredwithhospitalizationduringactivephaseofdisorderPsychosurgeryPsychotherapyDrugtherapiesDrugtherapiesaremainstayoftreatment.SchizophreniaDrugtherapiesDrugmedicationshavebeenavailablesincethemid-1950s.Theyhavegreatlyimprovedtheoutlookforindividualpatients.Thesemedicationsreducethepsychoticsymptomsofschizophreniaandusuallyallowthepatienttofunctionmoreeffectivelyandappropriately.Drugtherapiesarethebesttreatmentnowavailable,buttheydonot“cure”schizophreniaorensurethattherewillbenofurtherpsychoticepisodes.SchizophreniaDrugtherapiesDrugsthatcanbeusedtotreatschizophrenia.AntipsychoticDrugs.(Neuroleptics)(Tranquilisers)TraditionalantipsychoticsAtypicalantipsychoticsClassificationofAntipsychoticsgroupexamplesTraditionalantipsychotics(classicalneuroleptics)basal(sedative)antipsychoticschlorpromazine,chlorprotixene,clopenthixole,levopromazine,periciazine,thioridazineincisiveantipsychoticsdroperidole,flupentixol,fluphenazine,fluspirilene,haloperidol,melperone,oxyprothepine,penfluridol,perphenazine,pimozide,prochlorperazine,trifluoperazineAtypicalantipsychotics(antipsychoticsof2ndgeneration)amisulpiride,clozapine,olanzapine,quetiapine,risperidone,sertindole,sulpirideSchizophreniaTraditionalandatypicalantipsychoticsTraditionalAntipsychoticsonlyalleviatethepositivesymptoms;theytendtocauseextrapyrimidaleffectsalongwiththeirantipsychoticeffects.Atypicaldrugs,however,treatboththepositiveandnegativesymptomsLowerextrapyrimidaleffectsActon5HT2aswellasD2MoreexpensiveExtrapyrimidaleffectsLowerextrapyrimidaleffectsMechanismsofActionofAntipsychoticsTraditionalantipsychoticsD2receptorblockadeofpostsynapticinthe

mesolimbicpathwayAtypicalantipsychoticsD2receptorblockadeofpostsynapticin

themesolimbicpathwaytoreducepositivesymptoms;enhanceddopaminereleaseand5-HT2Areceptorblockadeinthe

mesocorticalpathwaytoreducenegativesymptoms;otherreceptor-bindingpropertiesmaycontributetoefficacyintreatingcognitivesymptoms,aggressivesymptomsanddepressioninschizophreniaReceptorSubtypesAffectedbyAtypicalAntipsychoticsrisperidoneD2,5-HT2A,5-HT7,1,2sertindoleD2,5-HT2A,5-HT2C,5-HT6,5-HT7,D3,1ziprasidoneD2,5-HT2A,5-HT1A,5-HT1D,5-HT2C,5-HT7,D3,1,NRI,SRIloxapineD2,5-HT2A,5-HT6,5-HT7,D1,D4,1,M1,H1,NRIzotepineD2,5-HT2A,5-HT2C,5-HT6,5-HT7,D1,D3,D4,1,H1,NRIclozapineD2,5-HT2A,5-HT1A,5-HT2C,5-HT3,5-HT6,5-HT7,D1,D3,D4,1,2,M1,H1olanzapineD2,5-HT2A,5-HT2C,5-HT3,5-HT6,D1,D3,D4,D5,1,M1-5,H1quetiapineD2,5-HT2A,5-HT6,5-HT7,1,2,H1SchizophreniaEtiologyMechanismTherapiesAnxietyAnxietyEveryonegetsanxiousorworriedsometimes.Butwhentoomuchanxietyinterfereswithnormalliving,thepersonmighthaveanAnxiety.PersistentanxietyforatleastonemonthCannotspecifythereasonsforanxietyOutofproportionstoanyrealisticconcernsaboutfamily,work,financesorhealthThataffectssociallifeManifestationsAnxietyAffectivesymptoms(feelingsofedginess,“losingcontrol”,“goingtodie”)Physicalsymptoms(tachycardia,tachypnea,diarrhea,diaphoresis,dizziness)Behavior(compulsions)Cognitions(worry,obsessions)Whatcausesanxiety?PsychologicalExternalCuesInternalCuesPhysicalExternalCuesInternalCuesStressfullifeeventsinduceanoveractiveneurobiologicalresponseWhatchangesinbrain?

electricalchanges

psychological physical changes

chemicalchanges BrainEventsHowdoesanxietyoccur?AnxiogenicstimulationStimulationNEand5-HTpathwaySeptohippocampalsystem(Anticipatedsignal)SeptumandhippocampusComparatorNormalstimulationBehavioralinhibitionIncreasedarousalandvigilanceActivationHypothalamusCentralgrayInhibitionAnxietyAmygdalaInhibitionInduceTherapiesAnxietyDrugtherapy(Anti-anxietydrugs)BenzodiazepinesOthersPsychotherapyAnti-anxietydrugsFirstlineforallanxietydisordersEffectiveandgenerallymorerapidactingthanotheranxiolyticsRiskforabuse,especiallyinpatientswithhistoryofsubstanceabuse(monitorclosely)Lowriskoflethalityinoverdose,exceptwhencombinedwithotherCNSdepressants(alcohol,barbiturates)Bindingtotheirreceptor-conformationalchange–increaseGABAreceptorchlorideinfluxandhyperpolarizationBenzodiazepinesAnti-anxietydrugsBenzodiazepinesUltrashortacting:Midazolam(Versed)Triazolam(Halcion)Shortacting:Alprazolam(Xanax)–greaterriskofabuseandwithdrawalOxazepam(Serax)Intermediateacting:Lorazepam(Ativan)Temazepam(Restoril)Longacting:Clonazepam(Klonopin)Diazepam(Valium)Chlordiazepoxide(Librium)Clorazepate(Tranxene)Flurazepam(Dalmane)DepressionDepressionEveryonefeelsloworsadsometimes,especiallyifthingsaren’tgoingwellforthem.Althoughpeoplemightsaytheyarefeelingdepressedthesefeelingsdon’tusuallylasttoolong.Whensomeonegets

DepressivedisorderorClinicalDepressionthesesadfeelingsaremuchstrongerthannormalandlastformuchlonger.Evenwhenthingsaregoingwellforthemtheystillfeelveryunhappy.DepressionWhenpeoplehavedepressivedisordertheyoften:Looksadandthinkeverythingishopeless.Cryalot.Sleepbadly.Don’tfeelhungryFeelmoreguiltyaboutthings.Thinkabouthurtingthemselves.Alwaysaskaboutsuicide!DepressionMajororUnipolarGeneralfeelingofsadness/“down”Negativeviewofself,worldandfutureBipolarManicstatewithperiodsofextreme“down”BiologicalCausesNegativeLifeExperiencesDepressionSocialRejectionWhatcausesdepression?CausesofDepressionSevereLifeEventsLossofimportantpeople(death,separation)Lossofimportantroles(job,promotion)PsychologicalFactorsCognitiveresponses(negativeselfview)LearnedhelplessnessBiologicalFactorsAbnormalneuraltransmissioninthebrain;hormonallevelsTwinstudiesshowhighheritabilityGenderDifferencesinDepressionTheviciouscycleofdepressioncanbebrokenatanypoint1Stressfulexperiences4Cognitiveandbehavioralchanges2Negativeexplanatorystyle3DepressedmoodTheviciouscycleofdepressionManicDepressionBipolarPETscansshowthatmanicdepressionbipolarstateDepressedstateManicstateDepressedstate(Unipolardepression)MechanismofdepressionDepressionisbelievedtoresultfromachemicalimbalanceinthebrain.Antidepressantdrugtherapymayhelprestorethatchemicalbalanceandrelievedepression.Whenapersonisdepressed,theirserotoninand/ornoradrenalinelevelarelow.Reserpine,whichcausesNAand5-HTtoleakoutofsynapticvesicleswheretheyaredestroyedbyenzymes,causesdepression.Lowerconcentrationsof5-H1AAinthebrainsofsuicidesMechanismofdepressionDepressionwasduetoadeficiencyofmonoamineneurotransmitters,norepinephrineandserotonin.Monoamineoxidaseinhibitors(MAOI)actasantidepressantsbyblockingofenzymeMAO,thusallowingpresynapticaccumulationofmonoamineneurotransmitters.Tricyclicantidepressantsactasantidepressantsbyblockingmembranetransportersensuringreuptakeof5-HTorNE,thuscausingincreasedextracellularneurotransmitterconcentrations.MechanismofdepressionCortisolisoftenincreasedindepressedpeople.IncreasedbloodflowtofrontallobesandamygdalaMedicationMAOIsincreasetheamount