Schizophrenia - Wikipedia

Schizophrenia is a mental disorder characterized by continuous or relapsing episodes of psychosis. ... Major symptoms include hallucinations (typically hearing ... Schizophrenia FromWikipedia,thefreeencyclopedia Jumptonavigation Jumptosearch Mentaldisordercharacterizedbypsychosis Forotheruses,seeSchizophrenia(disambiguation). MedicalconditionSchizophreniaClothembroideredbyapersondiagnosedwithschizophreniaPronunciation/ˌskɪtsəˈfriːniə/,UKalso/ˌskɪdzə-/,USalso/-ˈfrɛniə/[1]SpecialtyPsychiatrySymptomsHallucinations(usuallyhearingvoices),delusions,confusedthinking[2][3]ComplicationsSuicide,heartdisease,lifestylediseases[4]UsualonsetAges16to30[3]DurationChronic[3]CausesEnvironmentalandgeneticfactors[5]RiskfactorsFamilyhistory,cannabisuseinadolescence,problemsduringpregnancy,childhoodadversity,birthinlatewinterorearlyspring,olderfather,beingbornorraisedinacity[5][6]DiagnosticmethodBasedonobservedbehavior,reportedexperiences,andreportsofothersfamiliarwiththeperson[7]DifferentialdiagnosisSubstanceusedisorder,Huntington'sdisease,mooddisorders(bipolardisorder),autism,[8]borderlinepersonalitydisorder[9]ManagementCounseling,lifeskillstraining[2][5]MedicationAntipsychotics[5]Prognosis20–28yearsshorterlifeexpectancy[10][11]Deaths~17,000(2015)[12] Schizophreniaisamentaldisorder[13]characterizedbycontinuousorrelapsingepisodesofpsychosis.[5]Majorsymptomsincludehallucinations(typicallyhearingvoices),delusions,anddisorganizedthinking.[7]Othersymptomsincludesocialwithdrawal,decreasedemotionalexpression,andapathy.[5]Symptomstypicallydevelopgradually,beginduringyoungadulthood,andinmanycasesneverbecomeresolved.[3][7]Thereisnoobjectivediagnostictest;diagnosisisbasedonobservedbehavior,ahistorythatincludestheperson'sreportedexperiences,andreportsofothersfamiliarwiththeperson.[7]Tobediagnosedwithschizophrenia,symptomsandfunctionalimpairmentneedtobepresentforsixmonths(DSM-5)oronemonth(ICD-11).[7][14]Manypeoplewithschizophreniahaveothermentaldisorders,especiallysubstanceusedisorders,depressivedisorders,anxietydisorders,andobsessive–compulsivedisorder.[7] About0.3%to0.7%ofpeoplearediagnosedwithschizophreniaduringtheirlifetime.[15]In2017,therewereanestimated1.1millionnewcasesandin2022atotalof24millioncasesglobally.[2][16]Malesaremoreoftenaffectedandonaveragehaveanearlieronset.[2]Thecausesofschizophreniaincludegeneticandenvironmentalfactors.[5]Geneticfactorsincludeavarietyofcommonandraregeneticvariants.[17]Possibleenvironmentalfactorsincludebeingraisedinacity,cannabisuseduringadolescence,infections,theagesofaperson'smotherorfather,andpoornutritionduringpregnancy.[5][18] Abouthalfofthosediagnosedwithschizophreniawillhaveasignificantimprovementoverthelongtermwithnofurtherrelapses,andasmallproportionofthesewillrecovercompletely.[7][19]Theotherhalfwillhavealifelongimpairment.[20]Inseverecasespeoplemaybeadmittedtohospitals.[19]Socialproblemssuchaslong-termunemployment,poverty,homelessness,exploitation,andvictimizationarecommonlycorrelatedwithschizophrenia.[21][22]Comparedtothegeneralpopulation,peoplewithschizophreniahaveahighersuiciderate(about5%overall)andmorephysicalhealthproblems,[23][24]leadingtoanaveragedecreaseinlifeexpectancyby20[10]to28years.[11]In2015,anestimated17,000deathswerelinkedtoschizophrenia.[12] Themainstayoftreatmentisantipsychoticmedication,alongwithcounseling,jobtraining,andsocialrehabilitation.[5]Uptoathirdofpeopledonotrespondtoinitialantipsychotics,inwhichcaseclozapinemaybeused.[25]Inanetworkcomparativemeta-analysisof15antipsychoticdrugs,clozapinewassignificantlymoreeffectivethanallotherdrugs,althoughclozapine'sheavilymultimodalactionmaycausemoresideeffects.[26]Insituationswheredoctorsjudgethatthereisariskofharmtoselforothers,theymayimposeshortinvoluntaryhospitalization.[27]Long-termhospitalizationisusedonasmallnumberofpeoplewithsevereschizophrenia.[28]Insomecountrieswheresupportiveservicesarelimitedorunavailable,long-termhospitalstaysaremorecommon.[29] Contents 1Signsandsymptoms 1.1Positivesymptoms 1.2Negativesymptoms 1.3Cognitivesymptoms 1.4Onset 2Riskfactors 2.1Genetic 2.2Environmental 2.2.1Substanceuse 3Mechanism 4Diagnosis 4.1Criteria 4.2Comorbidities 4.3Differentialdiagnosis 5Prevention 6Management 6.1Medication 6.1.1Adverseeffects 6.2Psychosocialinterventions 6.3Other 7Prognosis 7.1Violence 8Epidemiology 9History 9.1Conceptualdevelopment 9.2Breadthofdiagnosis 9.3Historicaltreatment 9.4Politicalabuse 10Societyandculture 10.1Culturaldepictions 11Researchdirections 12Notes 13References 14Externallinks Signsandsymptoms MyEyesattheMomentoftheApparitionsbyGermanartistAugustNatterer,whohadschizophrenia Schizophreniaisamentaldisordercharacterizedbysignificantalterationsinperception,thoughts,mood,andbehavior.[30]Symptomsaredescribedintermsofpositive,negative,andcognitivesymptoms.[3][31]Thepositivesymptomsofschizophreniaarethesameforanypsychosisandaresometimesreferredtoaspsychoticsymptoms.Thesemaybepresentinanyofthedifferentpsychoses,andareoftentransientmakingearlydiagnosisofschizophreniaproblematic.Psychosisnotedforthefirsttimeinapersonwhoislaterdiagnosedwithschizophreniaisreferredtoasafirst-episodepsychosis(FEP).[32][33] Positivesymptoms Positivesymptomsarethosesymptomsthatarenotnormallyexperienced,butarepresentinpeopleduringapsychoticepisodeinschizophrenia.Theyincludedelusions,hallucinations,anddisorganizedthoughtsandspeech,typicallyregardedasmanifestationsofpsychosis.[32]Hallucinationsoccuratsomepointinthelifetimesof80%ofthosewithschizophrenia[34]andmostcommonlyinvolvethesenseofhearing(mostoftenhearingvoices)butcansometimesinvolveanyoftheothersensesoftaste,sight,smell,andtouch.[35]Thefrequencyofhallucinationsinvolvingmultiplesensesisdoubletherateofthoseinvolvingonlyonesense.[34]Theyarealsotypicallyrelatedtothecontentofthedelusionaltheme.[36]Delusionsarebizarreorpersecutoryinnature.Distortionsofself-experiencesuchasfeelingasifone'sthoughtsorfeelingsarenotreallyone'sown,tobelievingthatthoughtsarebeinginsertedintoone'smind,sometimestermedpassivityphenomena,arealsocommon.[37]Thoughtdisorderscanincludethoughtblocking,anddisorganizedspeech.[3]Positivesymptomsgenerallyrespondwelltomedication,[5]andbecomereducedoverthecourseoftheillness,perhapsrelatedtotheage-relateddeclineindopamineactivity.[7] Negativesymptoms Negativesymptomsaredeficitsofnormalemotionalresponses,orofotherthoughtprocesses.Thefiverecognizeddomainsofnegativesymptomsare:bluntedaffect–showingflatexpressionsorlittleemotion;alogia–apovertyofspeech;anhedonia–aninabilitytofeelpleasure;asociality–thelackofdesiretoformrelationships,andavolition–alackofmotivationandapathy.[38][39]Avolitionandanhedoniaareseenasmotivationaldeficitsresultingfromimpairedrewardprocessing.[40][41]Rewardisthemaindriverofmotivationandthisismostlymediatedbydopamine.[41]Ithasbeensuggestedthatnegativesymptomsaremultidimensionalandtheyhavebeencategorisedintotwosubdomainsofapathyorlackofmotivation,anddiminishedexpression.[38][42]Apathyincludesavolition,anhedonia,andsocialwithdrawal;diminishedexpressionincludesbluntaffect,andalogia.[43]Sometimesdiminishedexpressionistreatedasbothverbalandnon-verbal.[44] Apathyaccountsforaround50percentofthemostoftenfoundnegativesymptomsandaffectsfunctionaloutcomeandsubsequentqualityoflife.Apathyisrelatedtodisruptedcognitiveprocessingaffectingmemoryandplanningincludinggoal-directedbehaviour.[45]Thetwosubdomainshavesuggestedaneedforseparatetreatmentapproaches.[46]Alackofdistress–relatingtoareducedexperienceofdepressionandanxietyisanothernotednegativesymptom.[47]Adistinctionisoftenmadebetweenthosenegativesymptomsthatareinherenttoschizophrenia,termedprimary;andthosethatresultfrompositivesymptoms,fromthesideeffectsofantipsychotics,substanceusedisorder,andsocialdeprivation–termedsecondarynegativesymptoms.[48]Negativesymptomsarelessresponsivetomedicationandthemostdifficulttotreat.[46]However,ifproperlyassessed,secondarynegativesymptomsareamenabletotreatment.[42] Scalesforspecificallyassessingthepresenceofnegativesymptoms,andformeasuringtheirseverity,andtheirchangeshavebeenintroducedsincetheearlierscalessuchasthePANNSthatdealswithalltypesofsymptoms.[46]ThesescalesaretheClinicalAssessmentInterviewforNegativeSymptoms(CAINS),andtheBriefNegativeSymptomScale(BNSS)alsoknownassecond-generationscales.[46][47][49]In2020,tenyearsafteritsintroduction,across-culturalstudyoftheuseofBNSSfoundvalidandreliablepsychometricevidenceforthefive-domainstructurecross-culturally.[47]TheBNSSisdesignedtoassessboththepresenceandseverityandchangeofnegativesymptomsofthefiverecognizeddomains,andtheadditionalitemofreducednormaldistress.[47]BNSScanregisterchangesinnegativesymptomsconcerningpsychosocialandpharmacologicalinterventiontrials.BNSShasalsobeenusedtostudyaproposednon-D2treatmentcalledSEP-363856.Findingssupportedthefavouringoffivedomainsoverthetwo-dimensionalproposition.[47] Cognitivesymptoms Seealso:Visualprocessingabnormalitiesinschizophrenia Anestimated70%ofthosewithschizophreniahavecognitivedeficits,andthesearemostpronouncedinearlyonsetandlate-onsetillness.[50][51]Theseareoftenevidentlongbeforetheonsetofillnessintheprodromalstage,andmaybepresentinearlyadolescence,orchildhood.[52][53]Theyareacorefeaturebutnotconsideredtobecoresymptoms,asarepositiveandnegativesymptoms.[54][55]However,theirpresenceanddegreeofdysfunctionistakenasabetterindicatoroffunctionalitythanthepresentationofcoresymptoms.[52]Cognitivedeficitsbecomeworseatfirstepisodepsychosisbutthenreturntobaseline,andremainfairlystableoverthecourseoftheillness.[56][57] Thedeficitsincognitionareseentodrivethenegativepsychosocialoutcomeinschizophrenia,andareclaimedtoequatetoapossiblereductioninIQfromthenormof100to70–85.[58][59]Cognitivedeficitsmaybeofneurocognition(nonsocial)orofsocialcognition.[50]Neurocognitionistheabilitytoreceiveandrememberinformation,andincludesverbalfluency,memory,reasoning,problemsolving,speedofprocessing,andauditoryandvisualperception.[57]Verbalmemoryandattentionareseentobethemostaffected.[59][60]Verbalmemoryimpairmentisassociatedwithadecreasedlevelofsemanticprocessing(relatingmeaningtowords).[61]Anothermemoryimpairmentisthatofepisodicmemory.[62]Animpairmentinvisualperceptionthatisconsistentlyfoundinschizophreniaisthatofvisualbackwardmasking.[57]Visualprocessingimpairmentsincludeaninabilitytoperceivecomplexvisualillusions.[63]Socialcognitionisconcernedwiththementaloperationsneededtointerpret,andunderstandtheselfandothersinthesocialworld.[57][50]Thisisalsoanassociatedimpairment,andfacialemotionperceptionisoftenfoundtobedifficult.[64][65]Facialperceptioniscriticalforordinarysocialinteraction.[66]Cognitiveimpairmentsdonotusuallyrespondtoantipsychotics,andthereareanumberofinterventionsthatareusedtotrytoimprovethem;cognitiveremediationtherapyisofparticularhelp.[55] Neurologicalsoftsignsofclumsinessandlossoffinemotormovementareoftenfoundinschizophrenia,whichmayresolvewitheffectivetreatmentofFEP.[14][67] Onset Furtherinformation:Basicsymptomsofschizophrenia Seealso:ChildhoodschizophreniaandAdolescence§ Changesinthebrain Onsettypicallyoccursbetweenthelateteensandearly30s,withthepeakincidenceoccurringinmalesintheearlytomidtwenties,andinfemalesinthelatetwenties.[3][7][14]Onsetbeforetheageof17isknownasearly-onset,[68]andbeforetheageof13,ascansometimesoccur,isknownaschildhoodschizophreniaorveryearly-onset.[7][69]Onsetcanoccurbetweentheagesof40and60,knownaslate-onsetschizophrenia.[50]Onsetovertheageof60,whichmaybedifficulttodifferentiateasschizophrenia,isknownasvery-late-onsetschizophrenia-likepsychosis.[50]Lateonsethasshownthatahigherrateoffemalesareaffected;theyhavelessseveresymptomsandneedlowerdosesofantipsychotics.[50]Thetendencyforearlieronsetinmalesislaterseentobebalancedbyapost-menopausalincreaseinthedevelopmentinfemales.Estrogenproducedpre-menopausehasadampeningeffectondopaminereceptorsbutitsprotectioncanbeoverriddenbyageneticoverload.[70]Therehasbeenadramaticincreaseinthenumbersofolderadultswithschizophrenia.[71] Onsetmayhappensuddenlyormayoccuraftertheslowandgradualdevelopmentofanumberofsignsandsymptoms,aperiodknownastheprodromalstage.[7]Upto75%ofthosewithschizophreniagothroughaprodromalstage.[72]ThenegativeandcognitivesymptomsintheprodromestagecanprecedeFEP(firstepisodepsychosis)bymanymonthsanduptofiveyears.[56][73]TheperiodfromFEPandtreatmentisknownasthedurationofuntreatedpsychosis(DUP)whichisseentobeafactorinfunctionaloutcome.Theprodromalstageisthehigh-riskstageforthedevelopmentofpsychosis.[57]Sincetheprogressiontofirstepisodepsychosisisnotinevitable,analternativetermisoftenpreferredofatriskmentalstate.[57]Cognitivedysfunctionatanearlyageimpactsayoungperson'susualcognitivedevelopment.[74]Recognitionandearlyinterventionattheprodromalstagewouldminimizetheassociateddisruptiontoeducationalandsocialdevelopmentandhasbeenthefocusofmanystudies.[56][73] Riskfactors Mainarticle:Riskfactorsofschizophrenia Schizophreniaisdescribedasaneurodevelopmentaldisorderwithnopreciseboundary,orsinglecause,andisthoughttodevelopfromgene–environmentinteractionswithinvolvedvulnerabilityfactors.[5][75][76]Theinteractionsoftheseriskfactorsarecomplex,asnumerousanddiverseinsultsfromconceptiontoadulthoodcanbeinvolved.[76]Ageneticpredispositiononitsown,withoutinteractingenvironmentalfactors,willnotgiverisetothedevelopmentofschizophrenia.[76][77]Thegeneticcomponentmeansthatprenatalbraindevelopmentisdisturbed,andenvironmentalinfluenceaffectsthepostnataldevelopmentofthebrain.[78]Evidencesuggeststhatgeneticallysusceptiblechildrenaremorelikelytobevulnerabletotheeffectsofenvironmentalriskfactors.[78] Genetic Estimatesoftheheritabilityofschizophreniaarebetween70%and80%,whichimpliesthat70%to80%oftheindividualdifferencesinrisktoschizophreniaisassociatedwithgenetics.[17][79]Theseestimatesvarybecauseofthedifficultyinseparatinggeneticandenvironmentalinfluences,andtheiraccuracyhasbeenqueried.[80][81]Thegreatestriskfactorfordevelopingschizophreniaishavingafirst-degreerelativewiththedisease(riskis6.5%);morethan40%ofidenticaltwinsofthosewithschizophreniaarealsoaffected.[82]Ifoneparentisaffectedtheriskisabout13%andifbothareaffectedtheriskisnearly50%.[79]However,theDSM-5indicatesthatmostpeoplewithschizophreniahavenofamilyhistoryofpsychosis.[7]Resultsofcandidategenestudiesofschizophreniahavegenerallyfailedtofindconsistentassociations,[83]andthegeneticlociidentifiedbygenome-wideassociationstudiesexplainonlyasmallfractionofthevariationinthedisease.[84] Manygenesareknowntobeinvolvedinschizophrenia,eachwithsmalleffectandunknowntransmissionandexpression.[17][85][86]Thesummationoftheseeffectsizesintoapolygenicriskscorecanexplainatleast7%ofthevariabilityinliabilityforschizophrenia.[87]Around5%ofcasesofschizophreniaareunderstoodtobeatleastpartiallyattributabletorarecopynumbervariations(CNVs);thesestructuralvariationsareassociatedwithknowngenomicdisordersinvolvingdeletionsat22q11.2(DiGeorgesyndrome)and17q12(17q12microdeletionsyndrome),duplicationsat16p11.2(mostfrequentlyfound)anddeletionsat15q11.2(Burnside–Butlersyndrome).[88]SomeoftheseCNVsincreasetheriskofdevelopingschizophreniabyasmuchas20-fold,andarefrequentlycomorbidwithautismandintellectualdisabilities.[88] ThegenesCRHR1andCRHBPareassociatedwiththeseverityofsuicidalbehavior.ThesegenescodeforstressresponseproteinsneededinthecontroloftheHPAaxis,andtheirinteractioncanaffectthisaxis.ResponsetostresscancauselastingchangesinthefunctionoftheHPAaxispossiblydisruptingthenegativefeedbackmechanism,homeostasis,andtheregulationofemotionleadingtoalteredbehaviors.[77] Thequestionofhowschizophreniacouldbeprimarilygeneticallyinfluenced,giventhatpeoplewithschizophreniahavelowerfertilityrates,isaparadox.Itisexpectedthatgeneticvariantsthatincreasetheriskofschizophreniawouldbeselectedagainstduetotheirnegativeeffectsonreproductivefitness.Anumberofpotentialexplanationshavebeenproposed,includingthatallelesassociatedwithschizophreniariskconfersafitnessadvantageinunaffectedindividuals.[89][90]Whilesomeevidencehasnotsupportedthisidea,[81]othersproposethatalargenumberofalleleseachcontributingasmallamountcanpersist.[91] Ameta-analysisfoundthatoxidativeDNAdamagewassignificantlyincreasedinschizophrenia.[92] Environmental Furtherinformation:Prenatalnutrition,Prenatalstress,andNeuroplasticeffectsofpollution Environmentalfactors,eachassociatedwithaslightriskofdevelopingschizophreniainlaterlifeincludeoxygendeprivation,infection,prenatalmaternalstress,andmalnutritioninthemotherduringprenataldevelopment.[93]Ariskisassociatedwithmaternalobesity,inincreasingoxidativestress,anddysregulatingthedopamineandserotoninpathways.[94]Bothmaternalstressandinfectionhavebeendemonstratedtoalterfetalneurodevelopmentthroughanincreaseofpro-inflammatorycytokines.[95]ThereisaslighterriskassociatedwithbeingborninthewinterorspringpossiblyduetovitaminDdeficiency[96]oraprenatalviralinfection.[82]OtherinfectionsduringpregnancyoraroundthetimeofbirththathavebeenlinkedtoanincreasedriskincludeinfectionsbyToxoplasmagondiiandChlamydia.[97]Theincreasedriskisaboutfivetoeightpercent.[98]Viralinfectionsofthebrainduringchildhoodarealsolinkedtoariskofschizophreniaduringadulthood.[99] Adversechildhoodexperiences(ACEs),severeformsofwhichareclassedaschildhoodtrauma,rangefrombeingbulliedorabused,tothedeathofaparent.[100]Manyadversechildhoodexperiencescancausetoxicstressandincreasetheriskofpsychosis.[100][101][102]Chronictraumacanpromotelastinginflammatorydysregulationthroughoutthenervoussystem.[103]Itissuggestedthatearlystressmaycontributetothedevelopmentofschizophreniathroughthesealterationsintheimmunesystem.[103]SchizophreniawasthelastdiagnosistobenefitfromthelinkmadebetweenACEsandadultmentalhealthoutcomes.[104] Livinginanurbanenvironmentduringchildhoodorasanadulthasconsistentlybeenfoundtoincreasetheriskofschizophreniabyafactoroftwo,[23][105]evenaftertakingintoaccountdruguse,ethnicgroup,andsizeofsocialgroup.[106]Apossiblelinkbetweentheurbanenvironmentandpollutionhasbeensuggestedtobethecauseoftheelevatedriskofschizophrenia.[107]Otherriskfactorsincludesocialisolation,immigrationrelatedtosocialadversityandracialdiscrimination,familydysfunction,unemployment,andpoorhousingconditions.[82][108]Havingafatherolderthan40years,orparentsyoungerthan20yearsarealsoassociatedwithschizophrenia.[5][109] Substanceuse Furtherinformation:Riskfactorsofschizophrenia§ Substanceuse,andSubstance-inducedpsychosis Abouthalfofthosewithschizophreniauserecreationaldrugs,includingcannabis,tobacco,andalcoholexcessively.[110][111]Useofstimulantssuchasamphetamineandcocainecanleadtoatemporarystimulantpsychosis,whichpresentsverysimilarlytoschizophrenia.Rarely,alcoholusecanalsoresultinasimilaralcohol-relatedpsychosis.[82][112]Drugsmayalsobeusedascopingmechanismsbypeoplewhohaveschizophrenia,todealwithdepression,anxiety,boredom,andloneliness.[110][113]Theuseofcannabisandtobaccoarenotassociatedwiththedevelopmentofcognitivedeficits,andsometimesareverserelationshipisfoundwheretheiruseimprovesthesesymptoms.[55]However,substanceusedisordersareassociatedwithanincreasedriskofsuicide,andapoorresponsetotreatment.[114] Cannabisusemaybeacontributoryfactorinthedevelopmentofschizophrenia,potentiallyincreasingtheriskofthediseaseinthosewhoarealreadyatrisk.[115][116][117]Theincreasedriskmayrequirethepresenceofcertaingeneswithinanindividual.[18]Itsuseisassociatedwithdoublingtherate.[118] Mechanism Mainarticle:MechanismsofschizophreniaSeealso:Aberrantsalience Themechanismsofschizophreniaareunknown,andanumberofmodelshavebeenputforwardtoexplainthelinkbetweenalteredbrainfunctionandschizophrenia.[23]Theprevailingmodelofschizophreniaisthatofaneurodevelopmentaldisorder,andtheunderlyingchangesthatoccurbeforesymptomsbecomeevidentareseenasarisingfromtheinteractionbetweengenesandtheenvironment.[119]Extensivestudiessupportthismodel.[72]Maternalinfections,malnutritionandcomplicationsduringpregnancyandchildbirthareknownriskfactorsforthedevelopmentofschizophrenia,whichusuallyemergesbetweentheagesof18–25,aperiodthatoverlapswithcertainstagesofneurodevelopment.[120]Gene-environmentinteractionsleadtodeficitsintheneuralcircuitrythataffectsensoryandcognitivefunctions.[72] Thecommondopamineandglutamatemodelsproposedarenotmutuallyexclusive;eachisseentohavearoleintheneurobiologyofschizophrenia.[121]Themostcommonmodelputforwardwasthedopaminehypothesisofschizophrenia,whichattributespsychosistothemind'sfaultyinterpretationofthemisfiringofdopaminergicneurons.[122]Thishasbeendirectlyrelatedtothesymptomsofdelusionsandhallucinations.[123][124][125]Abnormaldopaminesignalinghasbeenimplicatedinschizophreniabasedontheusefulnessofmedicationsthataffectthedopaminereceptorandtheobservationthatdopaminelevelsareincreasedduringacutepsychosis.[126][127]AdecreaseinD1receptorsinthedorsolateralprefrontalcortexmayalsoberesponsiblefordeficitsinworkingmemory.[128][129] Theglutamatehypothesisofschizophrenialinksalterationsbetweenglutamatergicneurotransmissionandtheneuraloscillationsthataffectconnectionsbetweenthethalamusandthecortex.[130]Studieshaveshownthatareducedexpressionofaglutamatereceptor–NMDAreceptor,andglutamateblockingdrugssuchasphencyclidineandketaminecanmimicthesymptomsandcognitiveproblemsassociatedwithschizophrenia.[130][131][132]Post-mortemstudiesconsistentlyfindthatasubsetoftheseneuronsfailtoexpressGAD67(GAD1),[133]inadditiontoabnormalitiesinbrainmorphometry.Thesubsetsofinterneuronsthatareabnormalinschizophreniaareresponsibleforthesynchronizingofneuralensemblesneededduringworkingmemorytasks.Thesegivetheneuraloscillationsproducedasgammawavesthathaveafrequencyofbetween30and80hertz.Bothworkingmemorytasksandgammawavesareimpairedinschizophrenia,whichmayreflectabnormalinterneuronfunctionality.[133][134][135][136]Animportantprocessthatmaybedisruptedinneurodevelopmentisastrogenesis–theformationofastrocytes.Astrocytesarecrucialincontributingtotheformationandmaintenanceofneuralcircuitsanditisbelievedthatdisruptioninthisrolecanresultinanumberofneurodevelopmentaldisordersincludingschizophrenia.[137]EvidencesuggeststhatreducednumbersofastrocytesindeepercorticallayersareassocociatedwithadiminishedexpressionofEAAT2,aglutamatetransporterinastrocytes;supportingtheglutamatehypothesis.[137] Deficitsinexecutivefunctions,suchasplanning,inhibition,andworkingmemory,arepervasiveinschizophrenia.Althoughthesefunctionsareseparable,theirdysfunctioninschizophreniamayreflectanunderlyingdeficitintheabilitytorepresentgoalrelatedinformationinworkingmemory,andtoutilizethistodirectcognitionandbehavior.[138][139]Theseimpairmentshavebeenlinkedtoanumberofneuroimagingandneuropathologicalabnormalities.Forexample,functionalneuroimagingstudiesreportevidenceofreducedneuralprocessingefficiency,wherebythedorsolateralprefrontalcortexisactivatedtoagreaterdegreetoachieveacertainlevelofperformancerelativetocontrolsonworkingmemorytasks.Theseabnormalitiesmaybelinkedtotheconsistentpost-mortemfindingofreducedneuropil,evidencedbyincreasedpyramidalcelldensityandreduceddendriticspinedensity.Thesecellularandfunctionalabnormalitiesmayalsobereflectedinstructuralneuroimagingstudiesthatfindreducedgreymattervolumeinassociationwithdeficitsinworkingmemorytasks.[140] Positivesymptomshavebeenlinkedtocorticalthinninginthesuperiortemporalgyrus.[141]Severityofnegativesymptomshasbeenlinkedtoreducedthicknessintheleftmedialorbitofrontalcortex.[142]Anhedonia,traditionallydefinedasareducedcapacitytoexperiencepleasure,isfrequentlyreportedinschizophrenia.However,alargebodyofevidencesuggeststhathedonicresponsesareintactinschizophrenia,[143]andthatwhatisreportedtobeanhedoniaisareflectionofdysfunctioninotherprocessesrelatedtoreward.[144]Overall,afailureofrewardpredictionisthoughttoleadtoimpairmentinthegenerationofcognitionandbehaviorrequiredtoobtainrewards,despitenormalhedonicresponses.[145] Anothertheorylinksabnormalbrainlateralizationtothedevelopmentofbeingleft-handedwhichissignificantlymorecommoninthosewithschizophrenia.[146]Thisabnormaldevelopmentofhemisphericasymmetryisnotedinschizophrenia.[147]Studieshaveconcludedthatthelinkisatrueandverifiableeffectthatmayreflectageneticlinkbetweenlateralizationandschizophrenia.[146][148] Bayesianmodelsofbrainfunctioninghavebeenutilizedtolinkabnormalitiesincellularfunctioningtosymptoms.[149][150]Bothhallucinationsanddelusionshavebeensuggestedtoreflectimproperencodingofpriorexpectations,therebycausingexpectationtoexcessivelyinfluencesensoryperceptionandtheformationofbeliefs.Inapprovedmodelsofcircuitsthatmediatepredictivecoding,reducedNMDAreceptoractivation,couldintheoryresultinthepositivesymptomsofdelusionsandhallucinations.[151][152][153] Diagnosis Mainarticle:Diagnosisofschizophrenia Criteria SchizophreniaisdiagnosedbasedoncriteriaineithertheDiagnosticandStatisticalManualofMentalDisorders(DSM)publishedbytheAmericanPsychiatricAssociationortheInternationalStatisticalClassificationofDiseasesandRelatedHealthProblems(ICD)publishedbytheWorldHealthOrganization(WHO).Thesecriteriausetheself-reportedexperiencesofthepersonandreportedabnormalitiesinbehavior,followedbyapsychiatricassessment.Thementalstatusexaminationisanimportantpartoftheassessment.[154]AnestablishedtoolforassessingtheseverityofpositiveandnegativesymptomsisthePositiveandNegativeSyndromeScale(PANSS).[155]Thishasbeenseentohaveshortcomingsrelatingtonegativesymptoms,andotherscales–theClinicalAssessmentInterviewforNegativeSymptoms(CAINS),andtheBriefNegativeSymptomsScale(BNSS)havebeenintroduced.[46]TheDSM-5,publishedin2013,givesaScaletoAssesstheSeverityofSymptomDimensionsoutliningeightdimensionsofsymptoms.[54] DSM-5statesthattobediagnosedwithschizophrenia,twodiagnosticcriteriahavetobemetovertheperiodofonemonth,withasignificantimpactonsocialoroccupationalfunctioningforatleastsixmonths.Oneofthesymptomsneedstobeeitherdelusions,hallucinations,ordisorganizedspeech.Asecondsymptomcouldbeoneofthenegativesymptoms,orseverelydisorganizedorcatatonicbehaviour.[7]Adifferentdiagnosisofschizophreniformdisordercanbemadebeforethesixmonthsneededforthediagnosisofschizophrenia.[7] InAustraliatheguidelinefordiagnosisisforsixmonthsormorewithsymptomssevereenoughtoaffectordinaryfunctioning.[156]IntheUKdiagnosisisbasedonhavingthesymptomsformostofthetimeforonemonth,withsymptomsthatsignificantlyaffecttheabilitytowork,study,ortocarryonordinarydailyliving,andwithothersimilarconditionsruledout.[157] TheICDcriteriaaretypicallyusedinEuropeancountries;theDSMcriteriaareusedpredominantlyintheUnitedStatesandCanada,andareprevailinginresearchstudies.Inpractice,agreementbetweenthetwosystemsishigh.[158]ThecurrentproposalfortheICD-11criteriaforschizophreniarecommendsaddingself-disorderasasymptom.[37] AmajorunresolveddifferencebetweenthetwodiagnosticsystemsisthatoftherequirementinDSMofanimpairedfunctionaloutcome.WHOforICDarguesthatnotallpeoplewithschizophreniahavefunctionaldeficitsandsothesearenotspecificforthediagnosis.[54] Comorbidities Manypeoplewithschizophreniamayhaveoneormoreothermentaldisorders,suchaspanicdisorder,obsessive–compulsivedisorder,orsubstanceusedisorder.Theseareseparatedisordersthatrequiretreatment.[7]Whencomorbidwithschizophrenia,substanceusedisorderandantisocialpersonalitydisorderbothincreasetheriskforviolence.[159]Comorbidsubstanceusedisorderalsoincreasesriskforsuicide.[114] Sleepdisordersoftenco-occurwithschizophrenia,andmaybeanearlysignofrelapse.[160]Sleepdisordersarelinkedwithpositivesymptomssuchasdisorganizedthinkingandcanadverselyaffectcorticalplasticityandcognition.[160]Theconsolidationofmemoriesisdisruptedinsleepdisorders.[161]Theyareassociatedwithseverityofillness,apoorprognosis,andpoorqualityoflife.[162][163]Sleeponsetandmaintenanceinsomniaisacommonsymptom,regardlessofwhethertreatmenthasbeenreceivedornot.[162]Geneticvariationshavebeenfoundassociatedwiththeseconditionsinvolvingthecircadianrhythm,dopamineandhistaminemetabolism,andsignaltransduction.[164]Limitedpositiveevidencehasbeenfoundfortheuseofacupunctureasanadd-on.[165] Differentialdiagnosis Seealso:DualdiagnosisandComparisonofbipolardisorderandschizophrenia Tomakeadiagnosisofschizophreniaotherpossiblecausesofpsychosisneedtobeexcluded.[166]: 858 Psychoticsymptomslastinglessthanamonthmaybediagnosedasbriefpsychoticdisorder,orasschizophreniformdisorder.PsychosisisnotedinOtherspecifiedschizophreniaspectrumandotherpsychoticdisordersasaDSM-5category.Schizoaffectivedisorderisdiagnosedifsymptomsofmooddisorderaresubstantiallypresentalongsidepsychoticsymptoms.Psychosisthatresultsfromageneralmedicalconditionorsubstanceistermedsecondarypsychosis.[7] Psychoticsymptomsmaybepresentinseveralotherconditions,includingbipolardisorder,[8]borderlinepersonalitydisorder,[9]substanceintoxication,substance-inducedpsychosis,andanumberofdrugwithdrawalsyndromes.Non-bizarredelusionsarealsopresentindelusionaldisorder,andsocialwithdrawalinsocialanxietydisorder,avoidantpersonalitydisorderandschizotypalpersonalitydisorder.Schizotypalpersonalitydisorderhassymptomsthataresimilarbutlessseverethanthoseofschizophrenia.[7]Schizophreniaoccursalongwithobsessive–compulsivedisorder(OCD)considerablymoreoftenthancouldbeexplainedbychance,althoughitcanbedifficulttodistinguishobsessionsthatoccurinOCDfromthedelusionsofschizophrenia.[167]Therecanbeconsiderableoverlapwiththesymptomsofpost-traumaticstressdisorder.[168] Amoregeneralmedicalandneurologicalexaminationmaybeneededtoruleoutmedicalillnesseswhichmayrarelyproducepsychoticschizophrenia-likesymptoms,suchasmetabolicdisturbance,systemicinfection,syphilis,HIV-associatedneurocognitivedisorder,epilepsy,limbicencephalitis,andbrainlesions.Stroke,multiplesclerosis,hyperthyroidism,hypothyroidism,anddementiassuchasAlzheimer'sdisease,Huntington'sdisease,frontotemporaldementia,andtheLewybodydementiasmayalsobeassociatedwithschizophrenia-likepsychoticsymptoms.[169]Itmaybenecessarytoruleoutadelirium,whichcanbedistinguishedbyvisualhallucinations,acuteonsetandfluctuatinglevelofconsciousness,andindicatesanunderlyingmedicalillness.Investigationsarenotgenerallyrepeatedforrelapseunlessthereisaspecificmedicalindicationorpossibleadverseeffectsfromantipsychoticmedication.Inchildrenhallucinationsmustbeseparatedfromtypicalchildhoodfantasies.[7]Itisdifficulttodistinguishchildhoodschizophreniafromautism.[69] Prevention Preventionofschizophreniaisdifficultastherearenoreliablemarkersforthelaterdevelopmentofthedisorder.[170]Itisunclearasof2011whethertreatingpatientsintheprodromephaseofschizophreniaprovidesbenefits.[needsupdate][171]: 43 Thereisadiscrepancybetweenthegrowthintheimplementationofearlyinterventionprogrammesforpsychosisandtheunderlyingempiricalevidence.[171]: 44  Thereissomeevidenceasof2009thatearlyinterventioninthosewithfirst-episodepsychosismayimproveshort-termoutcomes,butthereislittlebenefitfromthesemeasuresafterfiveyears.[needsupdate][23]Cognitivebehavioraltherapymayreducetheriskofpsychosisinthoseathighriskafterayear[172]andisrecommendedinthisgroup,bytheNationalInstituteforHealthandCareExcellence(NICE).[30]Anotherpreventivemeasureistoavoiddrugsthathavebeenassociatedwithdevelopmentofthedisorder,includingcannabis,cocaine,andamphetamines.[82] Antipsychoticsareprescribedfollowingafirst-episodepsychosis,andfollowingremissionapreventivemaintenanceuseiscontinuedtoavoidrelapse.However,itisrecognizedthatsomepeopledorecoverfollowingasingleepisodeandthatlong-termuseofantipsychoticswillnotbeneededbutthereisnowayofidentifyingthisgroup.[173] Management Mainarticle:Managementofschizophrenia Theprimarytreatmentofschizophreniaistheuseofantipsychoticmedications,oftenincombinationwithpsychosocialinterventionsandsocialsupports.[23][174]Communitysupportservicesincludingdrop-incenters,visitsbymembersofacommunitymentalhealthteam,supportedemployment,[175]andsupportgroupsarecommon.Thetimebetweentheonsetofpsychoticsymptomstobeinggiventreatment–thedurationofuntreatedpsychosis(DUP)–isassociatedwithapooreroutcomeinboththeshorttermandthelongterm.[176] Voluntaryorinvoluntaryadmissiontohospitalmaybeimposedbydoctorsandcourtswhodeemapersontobehavingasevereepisode.IntheUK,largementalhospitalstermedasylumsbegantobecloseddowninthe1950swiththeadventofantipsychotics,andwithanawarenessofthenegativeimpactoflong-termhospitalstaysonrecovery.[21]Thisprocesswasknownasdeinstitutionalization,andcommunityandsupportiveservicesweredevelopedinordertosupportthischange.ManyothercountriesfollowedsuitwiththeUSstartinginthe60s.[177]Therestillremainasmallergroupofpeoplewhodonotimproveenoughtobedischarged.[21][28]Insomecountriesthatlackthenecessarysupportiveandsocialservices,long-termhospitalstaysaremoreusual.[29] Medication Risperidone(tradenameRisperdal)isacommonatypicalantipsychoticmedication. Thefirst-linetreatmentforschizophreniaisanantipsychotic.Thefirst-generationantipsychotics,nowcalledtypicalantipsychotics,aredopamineantagoniststhatblockD2receptors,andaffecttheneurotransmissionofdopamine.Thosebroughtoutlater,thesecond-generationantipsychoticsknownasatypicalantipsychotics,canalsohaveeffectonanotherneurotransmitter,serotonin.Antipsychoticscanreducethesymptomsofanxietywithinhoursoftheirusebutforothersymptomstheymaytakeseveraldaysorweekstoreachtheirfulleffect.[32][178]Theyhavelittleeffectonnegativeandcognitivesymptoms,whichmaybehelpedbyadditionalpsychotherapiesandmedications.[179]Thereisnosingleantipsychoticsuitableforfirst-linetreatmentforeveryone,asresponsesandtolerancesvarybetweenpeople.[180]Stoppingmedicationmaybeconsideredafterasinglepsychoticepisodewheretherehasbeenafullrecoverywithnosymptomsfortwelvemonths.Repeatedrelapsesworsenthelong-termoutlookandtheriskofrelapsefollowingasecondepisodeishigh,andlong-termtreatmentisusuallyrecommended.[181][182] Abouthalfofthosewithschizophreniawillrespondfavourablytoantipsychotics,andhaveagoodreturnoffunctioning.[183]However,positivesymptomspersistinuptoathirdofpeople.Followingtwotrialsofdifferentantipsychoticsoversixweeks,thatalsoproveineffective,theywillbeclassedashavingtreatmentresistantschizophrenia(TRS),andclozapinewillbeoffered.[184][25]Clozapineisofbenefittoaroundhalfofthisgroupalthoughithasthepotentiallyserioussideeffectofagranulocytosis(loweredwhitebloodcellcount)inlessthan4%ofpeople.[23][82][185] About30to50percentofpeoplewithschizophreniadonotacceptthattheyhaveanillnessorcomplywiththeirrecommendedtreatment.[186]Forthosewhoareunwillingorunabletotakemedicationregularly,long-actinginjectionsofantipsychoticsmaybeused,[187]whichreducetheriskofrelapsetoagreaterdegreethanoralmedications.[188]Whenusedincombinationwithpsychosocialinterventions,theymayimprovelong-termadherencetotreatment.[189] Adverseeffects Furtherinformation:Antipsychotic§ Adverseeffects Extrapyramidalsymptoms,includingakathisia,areassociatedwithallcommerciallyavailableantipsychotictovaryingdegrees.[190]: 566 Thereislittleevidencethatsecondgenerationantipsychoticshavereducedlevelsofextrapyramidicalsymptomscomparedtotypicalantipsychotics.[190]: 566 Tardivedyskinesiacanoccurduetolong-termuseofantipsychotics,developingaftermonthsoryearsofuse.[191]Theantipsychoticclozapineisalsoassociatedwiththromboembolism(includingpulmonaryembolism),myocarditis,andcardiomyopathy. Psychosocialinterventions Furtherinformation:Managementofschizophrenia§ Psychosocial Anumberofpsychosocialinterventionsthatincludeseveraltypesofpsychotherapymaybeusefulinthetreatmentofschizophreniasuchas:familytherapy,[192]grouptherapy,cognitiveremediationtherapy(CRT),[193]cognitivebehavioraltherapy(CBT),andmetacognitivetraining.[194]Skillstraining,andhelpwithsubstanceuse,andweightmanagement–oftenneededasasideeffectofanantipsychotic–arealsooffered.[195]IntheUS,interventionsforfirstepisodepsychosishavebeenbroughttogetherinanoverallapproachknownascoordinatedspecialitycare(CSC)andalsoincludessupportforeducation.[32]IntheUKcareacrossallphasesisasimilarapproachthatcoversmanyofthetreatmentguidelinesrecommended.[30]Theaimistoreducethenumberofrelapsesandstaysinhospital.[192] Othersupportservicesforeducation,employment,andhousingareusuallyoffered.Forpeoplewithsevereschizophrenia,anddischargedfromastayinhospital,theseservicesareoftenbroughttogetherinanintegratedapproachtooffersupportinthecommunityawayfromthehospitalsetting.Inadditiontomedicinemanagement,housing,andfinances,assistanceisgivenformoreroutinematterssuchashelpwithshoppingandusingpublictransport.Thisapproachisknownasassertivecommunitytreatment(ACT)andhasbeenshowntoachievepositiveresultsinsymptoms,socialfunctioningandqualityoflife.[196][197]Anothermoreintenseapproachisknownasintensivecaremanagement(ICM).ICMisastagefurtherthanACTandemphasisessupportofhighintensityinsmallercaseloads,(lessthantwenty).Thisapproachistoprovidelong-termcareinthecommunity.StudiesshowthatICMimprovesmanyoftherelevantoutcomesincludingsocialfunctioning.[198] SomestudieshaveshownlittleevidencefortheeffectivenessofCBTineitherreducingsymptomsorpreventingrelapse.[199][200]However,otherstudieshavefoundthatCBTdoesimproveoverallpsychoticsymptoms(wheninusewithmedication)andithasbeenrecommendedinCanada,buthasbeenseentohavenoeffectonsocialfunction,relapse,orqualityoflife.[201]IntheUKitisrecommendedasanadd-ontherapyinthetreatmentofschizophrenia.[178][200]Artstherapiesareseentoimprovenegativesymptomsinsomepeople,andarerecommendedbyNICEintheUK.[178]Thisapproachiscriticisedashavingnotbeenwell-researched,[202][203]andartstherapiesarenotrecommendedinAustralianguidelinesforexample.[204]Peersupport,inwhichpeoplewithpersonalexperienceofschizophrenia,providehelptoeachother,isofunclearbenefit.[205] Other Exerciseincludingaerobicexercisehasbeenshowntoimprovepositiveandnegativesymptoms,cognition,workingmemory,andimprovequalityoflife.[206][207]Exercisehasalsobeenshowntoincreasethevolumeofthehippocampusinthosewithschizophrenia.Adecreaseinhippocampalvolumeisoneofthefactorslinkedtothedevelopmentofthedisease.[206]However,therestillremainstheproblemofincreasingmotivationfor,andmaintainingparticipationinphysicalactivity.[208]Supervisedsessionsarerecommended.[207]IntheUKhealthyeatingadviceisofferedalongsideexerciseprograms.[209] Aninadequatedietisoftenfoundinschizophrenia,andassociatedvitamindeficienciesincludingthoseoffolate,andvitaminDarelinkedtotheriskfactorsforthedevelopmentofschizophreniaandforearlydeathincludingheartdisease.[210][211]Thosewithschizophreniapossiblyhavetheworstdietofallthementaldisorders.LowerlevelsoffolateandvitaminDhavebeennotedassignificantlylowerinfirstepisodepsychosis.[210]Theuseofsupplementalfolateisrecommended.[212]Azincdeficiencyhasalsobeennoted.[213]VitaminB12isalsooftendeficientandthisislinkedtoworsesymptoms.SupplementationwithBvitaminshasbeenshowntosignificantlyimprovesymptoms,andtoputinreversesomeofthecognitivedeficits.[210]Itisalsosuggestedthatthenoteddysfunctioningutmicrobiotamightbenefitfromtheuseofprobiotics.[213] Prognosis Mainarticle:PrognosisofschizophreniaSeealso:Physicalhealthinschizophrenia Disability-adjustedlifeyearslostduetoschizophreniaper100,000 inhabitantsin2004  nodata  ≤ 185  185–197  197–207  207–218  218–229  229–240  240–251  251–262  262–273  273–284  284–295  ≥ 295 Schizophreniahasgreathumanandeconomiccosts.[5]Itdecreaseslifeexpectancybybetween20[10]and28years.[11]Thisisprimarilybecauseofitsassociationwithheartdisease,[214]diabetes,[11]obesity,poordiet,asedentarylifestyle,andsmoking,withanincreasedrateofsuicideplayingalesserrole.[10][215]Sideeffectsofantipsychoticsmayalsoincreasetherisk.[10] Almost40%ofthosewithschizophreniadiefromcomplicationsofcardiovasculardiseasewhichisseentobeincreasinglyassociated.[211]AnunderlyingfactorofsuddencardiacdeathmaybeBrugadasyndrome(BrS)–BrSmutationsthatoverlapwiththoselinkedwithschizophreniaarethecalciumchannelmutations.[211]BrSmayalsobedrug-inducedfromcertainantipsychoticsandantidepressants.[211]Primarypolydipsia,orexcessivefluidintake,isrelativelycommoninpeoplewithchronicschizophrenia.[216][217]Thismayleadtohyponatremiawhichcanbelife-threatening.Antipsychoticscanleadtoadrymouth,butthereareseveralotherfactorsthatmaycontributetothedisorder;itmayreducelifeexpectancyby13percent.[217]Barrierstoimprovingthemortalityrateinschizophreniaarepoverty,overlookingthesymptomsofotherillnesses,stress,stigma,andmedicationsideeffects.[218] Schizophreniaisamajorcauseofdisability.In2016,itwasclassedasthe12thmostdisablingcondition.[219]Approximately75%ofpeoplewithschizophreniahaveongoingdisabilitywithrelapses.[220]Somepeopledorecovercompletelyandothersfunctionwellinsociety.[221]Mostpeoplewithschizophrenialiveindependentlywithcommunitysupport.[23]About85%areunemployed.[5]Inpeoplewithafirstepisodeofpsychosisinschizophreniaagoodlong-termoutcomeoccursin31%,anintermediateoutcomein42%andapooroutcomein31%.[222]Malesareaffectedmoreoftenthanfemales,andhaveaworseoutcome.[223]Studiesshowingthatoutcomesforschizophreniaappearbetterinthedevelopingthanthedevelopedworld[224]havebeenquestioned.[225]Socialproblems,suchaslong-termunemployment,poverty,homelessness,exploitation,stigmatizationandvictimizationarecommonconsequences,andleadtosocialexclusion.[21][22] Thereisahigherthanaveragesuiciderateassociatedwithschizophreniaestimatedat5%to6%,mostoftenoccurringintheperiodfollowingonsetorfirsthospitaladmission.[14][24]Severaltimesmore(20to40%)attemptsuicideatleastonce.[7][96]Thereareavarietyofriskfactors,includingmalegender,depression,ahighIQ,[226]heavysmoking,[227]andsubstanceuse.[114]Repeatedrelapseislinkedtoanincreasedriskofsuicidalbehavior.[173]Theuseofclozapinecanreducetheriskofsuicide,andofaggression.[228] Astrongassociationbetweenschizophreniaandtobaccosmokinghasbeenshowninworldwidestudies.[229][230]Smokingisespeciallyhighinthosediagnosedwithschizophrenia,withestimatesrangingfrom80to90%beingregularsmokers,ascomparedto20%ofthegeneralpopulation.[230]Thosewhosmoketendtosmokeheavily,andadditionallysmokecigaretteswithhighnicotinecontent.[36]Someproposethatthisisinanefforttoimprovesymptoms.[231]Amongpeoplewithschizophreniauseofcannabisisalsocommon.[114] Schizophrenialeadstoanincreasedriskofdementia.[232] Violence Mostpeoplewithschizophreniaarenotaggressive,andaremorelikelytobevictimsofviolenceratherthanperpetrators.[7]Peoplewithschizophreniaarecommonlyexploitedandvictimizedbyviolentcrimeaspartofabroaderdynamicofsocialexclusion.[21][22]Peoplediagnosedwithschizophreniaarealsosubjecttoforceddruginjections,seclusion,andrestraintathighrates.[27][28] Theriskofviolencebypeoplewithschizophreniaissmall.Thereareminorsubgroupswheretheriskishigh.[159]Thisriskisusuallyassociatedwithacomorbiddisordersuchasasubstanceusedisorder–inparticularalcohol,orwithantisocialpersonalitydisorder.[159]Substanceusedisorderisstronglylinked,andotherriskfactorsarelinkedtodeficitsincognitionandsocialcognitionincludingfacialperceptionandinsightthatareinpartincludedintheoryofmindimpairments.[233][234]Poorcognitivefunctioning,decision-making,andfacialperceptionmaycontributetomakingawrongjudgementofasituationthatcouldresultinaninappropriateresponsesuchasviolence.[235]Theseassociatedriskfactorsarealsopresentinantisocialpersonalitydisorderwhichwhenpresentasacomorbiddisordergreatlyincreasestheriskofviolence.[236][237] Epidemiology Mainarticle:Epidemiologyofschizophrenia Deathspermillionpersonsduetoschizophreniain2012  0–0  1–1  2–2  3–3  4–6  7–20 In2017,[needsupdate]theGlobalBurdenofDiseaseStudyestimatedtherewere1.1millionnewcases;[16]in2022theWorldHealthOrganization(WHO)reportedatotalof24millioncasesglobally.[2]Schizophreniaaffectsaround0.3–0.7%ofpeopleatsomepointintheirlife.[15][11]Inareasofconflictthisfigurecanrisetobetween4.0and6.5%.[238]Itoccurs1.4 timesmorefrequentlyinmalesthanfemalesandtypicallyappearsearlierinmen.[82] Worldwide,schizophreniaisthemostcommonpsychoticdisorder.[51]Thefrequencyofschizophreniavariesacrosstheworld,[7]withincountries,[239]andatthelocalandneighborhoodlevel;[240]thisvariationinprevalencebetweenstudiesovertime,acrossgeographicallocations,andbygenderisashighasfivefold.[5] Schizophreniacausesapproximatelyonepercentofworldwidedisabilityadjustedlifeyears[needsupdate][82]andresultedin17,000deathsin2015.[12] In2000,[needsupdate]WHOfoundthepercentageofpeopleaffectedandthenumberofnewcasesthatdevelopeachyearisroughlysimilararoundtheworld,withage-standardizedprevalenceper100,000rangingfrom343inAfricato544inJapanandOceaniaformen,andfrom378inAfricato527inSoutheasternEuropeforwomen.[241] History Mainarticle:Historyofschizophrenia Conceptualdevelopment Mainarticle:Historyofschizophrenia§ Conceptualdevelopment Furtherinformation:Dementiapraecox Theterm"schizophrenia"wascoinedbyEugenBleuler. Accountsofaschizophrenia-likesyndromearerareinrecordsbeforethe19thcentury;theearliestcasereportswerein1797and1809.[242]Dementiapraecox,meaningprematuredementia,wasusedbyGermanpsychiatristHeinrichSchülein1886,andthenin1891byArnoldPickinacasereportofhebephrenia.In1893EmilKraepelinusedtheterminmakingadistinction,knownastheKraepeliniandichotomy,betweenthetwopsychoses–dementiapraecox,andmanicdepression(nowcalledbipolardisorder).[10]Whenitbecameevidentthatthedisorderwasnotadegenerativedementia,itwasrenamedschizophreniabyEugenBleulerin1908.[243] Thewordschizophreniatranslatesas'splittingofthemind'andisModernLatinfromtheGreekwordsschizein(σχίζειν,'tosplit')andphrēn,(φρήν,'mind')[244]Itsusewasintendedtodescribetheseparationoffunctionbetweenpersonality,thinking,memory,andperception.[243] Intheearly20thcentury,thepsychiatristKurtSchneidercategorizedthepsychoticsymptomsofschizophreniaintotwogroups–hallucinationsanddelusions.Thehallucinationswerelistedasspecifictoauditoryandthedelusionsincludedthoughtdisorders.Thesewereseenasimportantsymptoms,termedfirst-rank.Themostcommonfirst-ranksymptomwasfoundtobelongtothoughtdisorders.[page needed][245][page needed][246]In2013thefirst-ranksymptomswereexcludedfromtheDSM-5criteria;[247]whiletheymaynotbeusefulindiagnosingschizophrenia,theycanassistindifferentialdiagnosis.[248] Subtypesofschizophrenia–classifiedasparanoid,disorganized,catatonic,undifferentiated,andresidual–weredifficulttodistinguishandarenolongerrecognizedasseparateconditionsbyDSM-5(2013)orICD-11.[249][250][251] Breadthofdiagnosis Beforethe1960s,nonviolentpettycriminalsandwomenweresometimesdiagnosedwithschizophrenia,categorizingthelatterasillfornotperformingtheirdutieswithinpatriarchyaswivesandmothers.[252]Inthemid-to-late1960s,blackmenwerecategorizedas"hostileandaggressive"anddiagnosedasschizophrenicatmuchhigherrates,theircivilrightsandBlackPoweractivismlabeledasdelusions.[252][253] Intheearly1970sintheUS,thediagnosticmodelforschizophreniawasbroadandclinicallybasedusingDSMII.SchizophreniawasdiagnosedfarmoreintheUSthaninEuropewhichusedtheICD-9criteria.TheUSmodelwascriticisedforfailingtodemarcateclearlythosepeoplewithamentalillness.In1980DSMIIIwaspublishedandshowedashiftinfocusfromtheclinicallybasedbiopsychosocialmodeltoareason-basedmedicalmodel.[254]DSMIVbroughtanincreasedfocusonanevidence-basedmedicalmodel.[255] Historicaltreatment Mainarticle:Historyofschizophrenia§ Developmentoftreatmentsinthe20thcentury Amoleculeofchlorpromazine,thefirstantipsychoticdevelopedinthe1950s Inthe1930sanumberofshockprocedureswhichinducedseizures(convulsions)orcomaswereusedtotreatschizophrenia.[256]Insulinshockinvolvedinjectinglargedosesofinsulintoinducecomas,whichinturnproducedhypoglycemiaandconvulsions.[256][257]Theuseofelectricitytoinduceseizureswasinuseaselectroconvulsivetherapy(ECT)by1938.[258] Psychosurgery,includingthelobotomyandfrontallobotomy–carriedoutfromthe1930suntilthe1970sintheUnitedStates,anduntilthe1980sinFrance–arerecognizedasahumanrightsabuse.[259][260]Inthemid-1950sthefirsttypicalantipsychotic,chlorpromazine,wasintroduced,[261]followedinthe1970sbythefirstatypicalantipsychotic,clozapine.[262] Politicalabuse Furtherinformation:Politicalabuseofpsychiatry Fromthe1960suntil1989,psychiatristsintheUSSRandEasternBlocdiagnosedthousandsofpeoplewithsluggishschizophrenia,[263][264]withoutsignsofpsychosis,basedon"theassumptionthatsymptomswouldlaterappear".[265]Nowdiscredited,thediagnosisprovidedaconvenientwaytoconfinepoliticaldissidents.[266] Societyandculture Seealso:Socialconstructionofschizophrenia,Listofpeoplewithschizophrenia,andReligionandschizophrenia JohnNash,anAmericanmathematicianandjointrecipientofthe1994NobelMemorialPrizeinEconomicSciences,hadschizophrenia.Hislifewasthesubjectofthe1998book,ABeautifulMindbySylviaNasar. In2002,thetermforschizophreniainJapanwaschangedfromseishin-bunretsu-byō(精神分裂病,lit.'mind-splitdisease')totōgō-shitchō-shō(統合失調症,lit.'integration–dysregulationsyndrome')toreducestigma.[267]Thenewname,alsointerpretedas"integrationdisorder",wasinspiredbythebiopsychosocialmodel.[268]AsimilarchangewasmadeinSouthKoreain2012toattunementdisorder.[269] IntheUnitedStates,theannualcostofschizophrenia–includingdirectcosts(outpatient,inpatient,drugs,andlong-termcare)andnon-healthcarecosts(lawenforcement,reducedworkplaceproductivity,andunemployment)–wasestimatedat$62.7billionfortheyear2002.[270][a]IntheUKthecostin2016wasputat£11.8billionperyearwithathirdofthatfiguredirectlyattributabletothecostofhospital,socialcareandtreatment.[5] Culturaldepictions ThebookABeautifulMindchronicledthelifeofJohnForbesNashwhohadbeendiagnosedwithschizophreniaandwontheNobelMemorialPrizeinEconomicSciences.Thebookwasmadeintoafilmwiththesamename;anearlierdocumentaryfilmwasABrilliantMadness. In1964acasestudyofthreemalesdiagnosedwithschizophreniawhoeachhadthedelusionalbeliefthattheywereJesusChristwaspublishedasTheThreeChristsofYpsilanti;afilmwiththetitleThreeChristswasreleasedin2020.[273][274] Mediacoveragereinforcespublicperceptionofanassociationbetweenschizophreniaandviolence;[275]infilm,peoplewithschizophreniaarehighlylikelytobeportrayedasadangertoothers.[276]IntheUKguidelinesforreportingconditionsandawardcampaignshaveshownareductioninnegativereportingsince2013.[277] Researchdirections Seealso:Animalmodelsofschizophrenia A2015Cochranereviewfoundunclearevidenceofbenefitfrombrainstimulationtechniquestotreatthepositivesymptomsofschizophrenia,inparticularauditoryverbalhallucinations(AVHs).[278]Moststudiesfocusontranscranialdirect-currentstimulation(tDCM),andrepetitivetranscranialmagneticstimulation(rTMS).[279]TechniquesbasedonfocusedultrasoundfordeepbrainstimulationcouldprovideinsightforthetreatmentofAVHs.[279] Thestudyofpotentialbiomarkersthatwouldhelpindiagnosisandtreatmentofschizophreniaisanactiveareaofresearchasof2020.Possiblebiomarkersincludemarkersofinflammation,[95]neuroimaging,[280]brain-derivedneurotrophicfactor(BDNF),[281]andspeechanalysis.SomemarkerssuchasC-reactiveproteinareusefulindetectinglevelsofinflammationimplicatedinsomepsychiatricdisordersbuttheyarenotdisorder-specific.Otherinflammatorycytokinesarefoundtobeelevatedinfirstepisodepsychosisandacuterelapsethatarenormalizedaftertreatmentwithantipsychotics,andthesemaybeconsideredasstatemarkers.[282]Deficitsinsleepspindlesinschizophreniamayserveasamarkerofanimpairedthalamocorticalcircuit,andamechanismformemoryimpairment.[161]MicroRNAsarehighlyinfluentialinearlyneuronaldevelopment,andtheirdisruptionisimplicatedinseveralCNSdisorders;circulatingmicroRNAs(cimiRNAs)arefoundinbodyfluidssuchasbloodandcerebrospinalfluid,andchangesintheirlevelsareseentorelatetochangesinmicroRNAlevelsinspecificregionsofbraintissue.ThesestudiessuggestthatcimiRNAshavethepotentialtobeearlyandaccuratebiomarkersinanumberofdisordersincludingschizophrenia.[283][284] Notes ^A2007reviewstatedthatthe2002estimatewasstillthebestavailable,[271]anda2018reviewcitedthesame$62.7 billion.[272] References ^JonesD(2003)[1917].RoachP,HartmannJ,SetterJ(eds.).EnglishPronouncingDictionary.CambridgeUniversityPress.ISBN 978-3-12-539683-8. ^abcde"SchizophreniaFactsheet".WorldHealthOrganization.10January2022.Retrieved23August2022. ^abcdefg"Schizophrenia".Healthtopics.USNationalInstituteofMentalHealth.April2022.Retrieved22August2022. ^"Medicinaltreatmentofpsychosis/schizophrenia".SwedishAgencyforHealthTechnologyAssessmentandAssessmentofSocialServices(SBU).21November2012.Archivedfromtheoriginalon29June2017.Retrieved26June2017. ^abcdefghijklmnopOwenMJ,SawaA,MortensenPB(July2016)."Schizophrenia".Lancet.388(10039):86–97.doi:10.1016/S0140-6736(15)01121-6.PMC 4940219.PMID 26777917. ^GruebnerO,RappMA,AdliM,et al.(February2017)."Citiesandmentalhealth".DeutschesÄrzteblattInternational.114(8):121–127.doi:10.3238/arztebl.2017.0121.PMC 5374256.PMID 28302261. 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