10.03.

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SchizophreniaWikipedia,thefreeencyclopedia

Schizophrenia
FromWikipedia,thefreeencyclopedia

Schizophreniaisamentaldisordercharacterizedbyabnormalsocialbehaviorand
failuretounderstandreality.[2]Commonsymptomsincludeauditoryhallucinations,
avolition,delusions,reducedsocialengagementandemotionalexpressionandthought
disorders.[2][3]Peopleoftenhaveadditionalmentalhealthproblemssuchasanxiety
disorders,majordepressiveillnessorsubstanceusedisorder.[4]Symptomstypically
comeongradually,begininyoungadulthood,andlastalongtime.[3][5]
Thecauseofschizophreniaisbelievedtobeacombinationofenvironmentaland
geneticfactors.[6]Possibleenvironmentalfactorsincludebeingraisedinacity,cannabis
use,certaininfections,parentalageandpoornutritionduringpregnancy.[6][7]Diagnosis
isbasedonobservedbehaviorandtheperson'sreportedexperiences.[5]During
diagnosisaperson'sculturemustalsobetakenintoaccount.[5]Asof2013thereisno
objectivetest.[5]Schizophreniadoesnotimplya"splitpersonality"or"multiple
personalitydisorder"aconditionwithwhichitisoftenconfusedinpublic
perception.[8]
Themainstayoftreatmentisantipsychoticmedicationalongwithjobtraining,
psychotherapyandsocialrehabilitation.[2][6]Itisuncleariftypicaloratypical
antipsychoticsarebetter.[9]Inthosewhodonotimprovewithotherantipsychotics,
clozapinemaybeused.[6]Inmoreseriouscaseswherethereisrisktoselforothers
involuntaryhospitalizationmaybenecessary,althoughhospitalstaysarenowshorter
andlessfrequentthantheyoncewere.[10]
About0.30.7%ofpeopleareaffectedbyschizophreniaduringtheirlifetime.[11]In
2013therewasestimatedtobe23.6millioncasesglobally.[12]Malesaremoreoften
affectedthanfemales.[2]About20%ofpeopledowellandafewrecovercompletely.[5]
Socialproblems,suchaslongtermunemployment,poverty,andhomelessnessare
common.[5][13]Theaveragelifeexpectancyofpeoplewiththedisorderistentotwenty
fiveyearslessthantheaverage.[14]Thisistheresultofincreasedphysicalhealth
problemsandahighersuiciderate(about5%).[11][15]In2013anestimated16,000
peoplediedfrombehaviorrelatedtoorcausedbyschizophrenia.[16]

Contents

Schizophrenia

Owen,MJ
Sawa,A
Mortensen,PB(14
January2016).
"Schizophrenia.".
Selfportraitofapersonwithschizophrenia,representingthatindividual's
Lancet(London,
England).
perceptionofthedistortedexperienceofrealityinthedisorder
doi:10.1016/S0140
6736(15)011216.
Classificationandexternalresources
PMID26777917.

Pronunciation /sktsfrini,skdz,o,frni/[1]
Specialty

Psychiatry

ICD10

F20
(http://apps.who.int/classifications/icd10/browse/2015/en#/F20)

ICD9CM

295(http://www.icd9data.com/getICD9Code.ashx?icd9=295)

OMIM

181500(http://omim.org/entry/181500)

DiseasesDB

11890(http://www.diseasesdatabase.com/ddb11890.htm)

MedlinePlus

000928
(http://www.nlm.nih.gov/medlineplus/ency/article/000928.htm)

eMedicine

med/2072(http://www.emedicine.com/med/topic2072.htm)
emerg/520(http://www.emedicine.com/emerg/topic520.htm#)

PatientUK

Schizophrenia(http://patient.info/doctor/schizophreniapro)

MeSH

F03.700.750
(https://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?
mode=&term=Schizophrenia&field=entry#TreeF03.700.750)

1 Symptoms
1.1 Positiveandnegative
1.2 Cognitivedysfunction
1.3 Onset
2 Causes
2.1 Genetic
2.2 Environment
3 Mechanisms
3.1 Psychological
3.2 Neurological
4 Diagnosis
4.1 Criteria
4.2 Subtypes
4.3 Differentialdiagnosis
5 Prevention
6 Management
6.1 Medication
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6.2 Psychosocial
7 Prognosis
8 Epidemiology
9 History
10 Societyandculture
10.1 Violence
11 Researchdirections
12 References
13 Externallinks

Symptoms
Individualswithschizophreniamayexperiencehallucinations(mostreportedarehearingvoices),delusions(oftenbizarre
orpersecutoryinnature),anddisorganizedthinkingandspeech.Thelastmayrangefromlossoftrainofthought,to
sentencesonlylooselyconnectedinmeaning,tospeechthatisnotunderstandableknownaswordsalad.Socialwithdrawal,
sloppinessofdressandhygiene,andlossofmotivationandjudgmentareallcommoninschizophrenia.[17]Thereisoftenan
observablepatternofemotionaldifficulty,forexamplelackofresponsiveness.[18]Impairmentinsocialcognitionis
associatedwithschizophrenia,[19]asaresymptomsofparanoia.Socialisolationcommonlyoccurs.[20]Difficultiesin
workingandlongtermmemory,attention,executivefunctioning,andspeedofprocessingalsocommonlyoccur.[11]Inone
uncommonsubtype,thepersonmaybelargelymute,remainmotionlessinbizarrepostures,orexhibitpurposeless
agitation,allsignsofcatatonia.[21]About30to50%ofpeoplewithschizophreniafailtoacceptthattheyhaveanillnessor
theirrecommendedtreatment.[22]Treatmentmayhavesomeeffectoninsight.[23]Peoplewithschizophreniaoftenfind
facialemotionperceptiontobedifficult.[24]

Videoexplanationofschizophrenia

Peoplewithschizophreniamayhaveahighrateofirritablebowelsyndromebuttheyoftendonotmentionitunless
specificallyasked.[25]

Positiveandnegative
Schizophreniaisoftendescribedintermsofpositiveandnegative(ordeficit)symptoms.[26]Positivesymptomsarethose
thatmostindividualsdonotnormallyexperiencebutarepresentinpeoplewithschizophrenia.Theycanincludedelusions,
disorderedthoughtsandspeech,andtactile,auditory,visual,olfactoryandgustatoryhallucinations,typicallyregardedas
manifestationsofpsychosis.[27]Hallucinationsarealsotypicallyrelatedtothecontentofthedelusionaltheme.[28]Positive
symptomsgenerallyrespondwelltomedication.[28]

Myeyesatthemomentofthe
apparitionsbyGermanartistAugust
Nattererwhohadschizophrenia

Negativesymptomsaredeficitsofnormalemotionalresponsesorofotherthoughtprocesses,andarelessresponsivetomedication.[17]Theycommonlyinclude
flatexpressionsorlittleemotion,povertyofspeech,inabilitytoexperiencepleasure,lackofdesiretoformrelationships,andlackofmotivation.Negative
symptomsappeartocontributemoretopoorqualityoflife,functionalability,andtheburdenonothersthandopositivesymptoms.[29]Peoplewithgreaternegative
symptomsoftenhaveahistoryofpooradjustmentbeforetheonsetofillness,andresponsetomedicationisoftenlimited.[17][30]

Cognitivedysfunction
Deficitsincognitiveabilitiesarewidelyrecognizedasacorefeatureofschizophrenia.[31][32][33]Theextentofthecognitivedeficitsanindividualexperiencesisa
predictorofhowfunctionalanindividualwillbe,thequalityofoccupationalperformance,andhowsuccessfultheindividualwillbeinmaintainingtreatment.[34]
Thepresenceanddegreeofcognitivedysfunctioninindividualswithschizophreniahasbeenreportedtobeabetterindicatoroffunctionalitythanthepresentation
ofpositiveornegativesymptoms.[31]Thedeficitsimpactingthecognitivefunctionarefoundinalargenumberofareas:workingmemory,longterm
memory,[35][36]verbaldeclarativememory,[37]semanticprocessing,[38]episodicmemory,[34]attention,learning(particularlyverballearning).[35]Deficitsinverbal
memoryarethemostpronouncedinindividualswithschizophrenia,andarenotaccountedforbydeficitinattention.Verbalmemoryimpairmenthasbeenlinked
toadecreasedabilityinindividualswithschizophreniatosemanticallyencode(processinformationrelatingtomeaning),whichiscitedasacauseforanother
knowndeficitinlongtermmemory.[35]Whengivenalistofwords,healthyindividualsrememberpositivewordsmorefrequently(knownasthePollyanna
principle)however,individualswithschizophreniatendtorememberallwordsequallyregardlessoftheirconnotations,suggestingthattheexperienceof
anhedoniaimpairsthesemanticencodingofthewords.[35]Thesedeficitshavebeenfoundinindividualsbeforetheonsetoftheillnesstosomeextent.[31][33][39]
Firstdegreefamilymembersofindividualswithschizophreniaandotherhighriskindividualsalsoshowadegreeofdeficitincognitiveabilities,andspecifically
inworkingmemory.[39]Areviewoftheliteratureoncognitivedeficitsinindividualswithschizophreniashowthatthedeficitsmaybepresentinearly
adolescence,orasearlyaschildhood.[31]Thedeficitswhichanindividualwithschizophreniapresentstendtoremainthesameovertimeinmostpatients,or
followanidentifiablecoursebaseduponenvironmentalvariables.[31][35]
Althoughtheevidencethatcognitivedeficitsremainstableovertimeisreliableandabundant,[34][35]muchoftheresearchinthisdomainfocusesonmethodsto
improveattentionandworkingmemory[35][36]Effortstoimprovelearningabilityinindividualswithschizophreniausingahighvs.lowrewardconditionandan
instructionabsentorinstructionpresentconditionrevealedthatincreasingrewardleadstopoorerperformancewhileprovidinginstructionleadstoimproved
performance,highlightingthatsometreatmentsmayexisttoincreasecognitiveperformance.[35]Trainingindividualswithschizophreniatoaltertheirthinking,
attention,andlanguagebehaviorsbyverbalizingtasks,engagingincognitiverehearsal,givingselfinstructions,givingcopingstatementstotheselftohandle
failure,andprovidingselfreinforcementforsuccess,significantlyimprovesperformanceonrecalltasks.[35]Thistypeoftraining,knownasselfinstructional(SI)
training,producedbenefitssuchaslowernumberofnonsenseverbalizationsandimprovedrecallwhiledistracted.[35]

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Onset
Lateadolescenceandearlyadulthoodarepeakperiodsfortheonsetofschizophrenia,[11]criticalyearsinayoungadult'ssocialandvocationaldevelopment.[40]In
40%ofmenand23%ofwomendiagnosedwithschizophrenia,theconditionmanifesteditselfbeforetheageof19.[41]Tominimizethedevelopmentaldisruption
associatedwithschizophrenia,muchworkhasrecentlybeendonetoidentifyandtreattheprodromal(preonset)phaseoftheillness,whichhasbeendetectedupto
30monthsbeforetheonsetofsymptoms.[40]Thosewhogoontodevelopschizophreniamayexperiencetransientorselflimitingpsychoticsymptoms[42]andthe
nonspecificsymptomsofsocialwithdrawal,irritability,dysphoria,[43]andclumsiness[44]duringtheprodromalphase.

Causes
Acombinationofgeneticandenvironmentalfactorsplayaroleinthedevelopmentofschizophrenia.[8][11]Peoplewithafamilyhistoryofschizophreniawhohave
atransientpsychosishavea2040%chanceofbeingdiagnosedoneyearlater.[45]

Genetic
Estimatesofheritabilityvarybecauseofthedifficultyinseparatingtheeffectsofgeneticsandtheenvironment[46]averagesof0.80havebeengiven.[47]The
greatestriskfordevelopingschizophreniaishavingafirstdegreerelativewiththedisease(riskis6.5%)morethan40%ofmonozygotictwinsofthosewith
schizophreniaarealsoaffected.[8]Ifoneparentisaffectedtheriskisabout13%andifbothareaffectedtheriskisnearly50%.[47]
ManygenesarebelievedtobeinvolvedinSchizophrenia,eachofsmalleffectandunknowntransmissionandexpression.[8]Manypossiblecandidateshavebeen
proposed,includingspecificcopynumbervariations,NOTCH4,andhistoneproteinloci.[48]Anumberofgenomewideassociationssuchaszincfingerprotein
804Ahavealsobeenlinked.[49]Thereappearstobeoverlapinthegeneticsofschizophreniaandbipolardisorder.[50]Evidenceisemergingthatthegenetic
architectureofschizophreniainvolvedbothcommonandrareriskvariation.[51]
Assumingahereditarybasis,onequestionfromevolutionarypsychologyiswhygenesthatincreasethelikelihoodofpsychosisevolved,assumingthecondition
wouldhavebeenmaladaptivefromanevolutionarypointofview.Oneideaisthatgenesareinvolvedintheevolutionoflanguageandhumannature,buttodate
suchideasremainlittlemorethanhypotheticalinnature.[52][53]

Environment
Environmentalfactorsassociatedwiththedevelopmentofschizophreniaincludethelivingenvironment,druguseandprenatalstressors.[11]
Parentingstyleseemstohavenomajoreffect,althoughpeoplewithsupportiveparentsdobetterthanthosewithcriticalorhostileparents.[8]Childhoodtrauma,
deathofaparent,andbeingbulliedorabusedincreasetheriskofpsychosis.[54]Livinginanurbanenvironmentduringchildhoodorasanadulthasconsistently
beenfoundtoincreasetheriskofschizophreniabyafactoroftwo,[8][11]evenaftertakingintoaccountdruguse,ethnicgroup,andsizeofsocialgroup.[55]Other
factorsthatplayanimportantroleincludesocialisolationandimmigrationrelatedtosocialadversity,racialdiscrimination,familydysfunction,unemployment,
andpoorhousingconditions.[8][56]
Ithasbeenhypothesisedthatinsomepeople,developmentofschizophreniaisrelatedtointestinaltractdysfunctionsuchasseenwithnonceliacglutensensitivity
orabnormalitiesintheintestinalflora.[57]Asubgroupofpersonswithschizophreniapresentanimmuneresponsetogluten,differentfromthatfoundinpeople
withceliac,withelevatedlevelsofcertainserumbiomarkersofglutensensitivitysuchasantigliadinIgGorantigliadinIgAantibodies.[58]
Substanceuse
Abouthalfofthosewithschizophreniausedrugsoralcoholexcessively.[59]Amphetamine,cocaine,andtoalesserextentalcohol,canresultinpsychosisthat
presentsverysimilarlytoschizophrenia.[8][60]Althoughitisnotgenerallybelievedtobeacauseoftheillness,peoplewithschizophreniausenicotineatmuch
greaterratesthanthegeneralpopulation.[61]
Alcoholabusecanoccasionallycausethedevelopmentofachronicsubstanceinducedpsychoticdisorderviaakindlingmechanism.[62]Alcoholuseisnot
associatedwithanearlieronsetofpsychosis.[63]
Cannabiscanbeacontributoryfactorinschizophrenia,[7][64][65]potentiallycausingthediseaseinthosewhoarealreadyatrisk.[65]Theincreasedriskmayrequire
thepresenceofcertaingeneswithinanindividual[65]ormayberelatedtopreexistingpsychopathology.[7]Earlyexposureisstronglyassociatedwithanincreased
risk.[7]Thesizeoftheincreasedriskisnotclear[66]butappearstobeintherangeoftwotothreetimesgreaterforpsychosis.[64]Higherdosageandgreater
frequencyofuseareindicatorsofincreasedriskofchronicpsychoses.[64]
Otherdrugsmaybeusedonlyascopingmechanismsbyindividualswhohaveschizophreniatodealwithdepression,anxiety,boredom,andloneliness.[59][67]
Developmentalfactors
Factorssuchashypoxiaandinfection,orstressandmalnutritioninthemotherduringfetaldevelopment,mayresultinaslightincreaseintheriskofschizophrenia
laterinlife.[11]Peoplediagnosedwithschizophreniaaremorelikelytohavebeenborninwinterorspring(atleastinthenorthernhemisphere),whichmaybea
resultofincreasedratesofviralexposuresinutero.[8]Theincreasedriskisabout5to8%.[68]Otherinfectionsduringpregnancyoraroundthetimeofbirththat
mayincreasetheriskincludeToxoplasmagondiandChlamydia.[69]

Mechanisms
Anumberofattemptshavebeenmadetoexplainthelinkbetweenalteredbrainfunctionandschizophrenia.[11]Oneofthemostcommonisthedopamine
hypothesis,whichattributespsychosistothemind'sfaultyinterpretationofthemisfiringofdopaminergicneurons.[11]

Psychological
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Manypsychologicalmechanismshavebeenimplicatedinthedevelopmentandmaintenanceofschizophrenia.Cognitive
biaseshavebeenidentifiedinthosewiththediagnosisorthoseatrisk,especiallywhenunderstressorinconfusing
situations.[70]Somecognitivefeaturesmayreflectglobalneurocognitivedeficitssuchasmemoryloss,whileothersmaybe
relatedtoparticularissuesandexperiences.[71][72]

Clothembroideredbyaperson
diagnosedwithschizophrenia

Despiteademonstratedappearanceofbluntedaffect,recentfindingsindicatethatmanyindividualsdiagnosedwith
schizophreniaareemotionallyresponsive,particularlytostressfulornegativestimuli,andthatsuchsensitivitymaycause
vulnerabilitytosymptomsortothedisorder.[73][74]Someevidencesuggeststhatthecontentofdelusionalbeliefsand
psychoticexperiencescanreflectemotionalcausesofthedisorder,andthathowapersoninterpretssuchexperiencescan
influencesymptomatology.[75][76][77]Theuseof"safetybehaviors"(actssuchasgesturesortheuseofwordsinspecific
contexts)toavoidorneutralizeimaginedthreatsmayactuallycontributetothechronicityofdelusions.[78]Furtherevidence
fortheroleofpsychologicalmechanismscomesfromtheeffectsofpsychotherapiesonsymptomsofschizophrenia.[79]

Neurological
Schizophreniaisassociatedwithsubtledifferencesinbrainstructures,foundin40to50%ofcases,andinbrainchemistry
duringacutepsychoticstates.[11]StudiesusingneuropsychologicaltestsandbrainimagingtechnologiessuchasfMRIand
PETtoexaminefunctionaldifferencesinbrainactivityhaveshownthatdifferencesseemtomostcommonlyoccurinthe
frontallobes,hippocampusandtemporallobes.[80]Reductionsinbrainvolume,smallerthanthosefoundinAlzheimer's
disease,havebeenreportedinareasofthefrontalcortexandtemporallobes.Itisuncertainwhetherthesevolumetric
changesareprogressiveorexistpriortotheonsetofthedisease.[44]Thesedifferenceshavebeenlinkedtothe
neurocognitivedeficitsoftenassociatedwithschizophrenia.[81]Becauseneuralcircuitsarealtered,ithasalternativelybeen
suggestedthatschizophreniashouldbethoughtofasacollectionofneurodevelopmentaldisorders.[82]Therehasbeen
debateonwhethertreatmentwithantipsychoticscanitselfcausereductionofbrainvolume.[83]
Particularattentionhasbeenpaidtothefunctionofdopamineinthemesolimbicpathwayofthebrain.Thisfocuslargely
resultedfromtheaccidentalfindingthatphenothiazinedrugs,whichblockdopaminefunction,couldreducepsychotic
symptoms.Itisalsosupportedbythefactthatamphetamines,whichtriggerthereleaseofdopamine,mayexacerbatethe
psychoticsymptomsinschizophrenia.[84]Theinfluentialdopaminehypothesisofschizophreniaproposedthatexcessive
activationofD2receptorswasthecauseof(thepositivesymptomsof)schizophrenia.Althoughpostulatedforabout

Functionalmagneticresonance
imaging(fMRI)showingtwolevels
ofthebrainareasinorangewere
moreactiveinhealthycontrolsthan
inmedicatedpeoplewith
schizophrenia.

20yearsbasedontheD2blockadeeffectcommontoallantipsychotics,itwasnotuntilthemid1990sthatPETandSPET
imagingstudiesprovidedsupportingevidence.Thedopaminehypothesisisnowthoughttobesimplistic,partlybecause
newerantipsychoticmedication(atypicalantipsychoticmedication)canbejustaseffectiveasoldermedication(typical
antipsychoticmedication),butalsoaffectsserotoninfunctionandmayhaveslightlylessofadopamineblockingeffect.[85]
InteresthasalsofocusedontheneurotransmitterglutamateandthereducedfunctionoftheNMDAglutamatereceptorin
Schizophreniaisassociatedwith
schizophrenia,largelybecauseoftheabnormallylowlevelsofglutamatereceptorsfoundinthepostmortembrainsofthose
enlargedlateralventriclesinthe
diagnosedwithschizophrenia,[86]andthediscoverythatglutamateblockingdrugssuchasphencyclidineandketaminecan
brain.
mimicthesymptomsandcognitiveproblemsassociatedwiththecondition.[87]Reducedglutamatefunctionislinkedto
poorperformanceontestsrequiringfrontallobeandhippocampalfunction,andglutamatecanaffectdopaminefunction,bothofwhichhavebeenimplicatedin
schizophrenia,havesuggestedanimportantmediating(andpossiblycausal)roleofglutamatepathwaysinthecondition.[88]Butpositivesymptomsfailtorespond
toglutamatergicmedication.[89]

Diagnosis
SchizophreniaisdiagnosedbasedoncriteriaineithertheAmericanPsychiatricAssociation'sfiftheditionoftheDiagnosticand
StatisticalManualofMentalDisorders(DSM5),ortheWorldHealthOrganization'sInternationalStatisticalClassificationof
DiseasesandRelatedHealthProblems(ICD10).Thesecriteriausetheselfreportedexperiencesofthepersonandreported
abnormalitiesinbehavior,followedbyaclinicalassessmentbyamentalhealthprofessional.Symptomsassociatedwith
schizophreniaoccuralongacontinuuminthepopulationandmustreachacertainseveritybeforeadiagnosisismade.[8]Asof
2013thereisnoobjectivetest.[5]

Criteria
In2013,theAmericanPsychiatricAssociationreleasedthefiftheditionoftheDSM(DSM5).Tobediagnosedwithschizophrenia,
twodiagnosticcriteriahavetobemetovermuchofthetimeofaperiodofatleastonemonth,withasignificantimpactonsocialor
occupationalfunctioningforatleastsixmonths.Thepersonhadtobesufferingfromdelusions,hallucinationsordisorganized
speech.Asecondsymptomcouldbenegativesymptomsorseverelydisorganizedorcatatonicbehaviour.[90]Thedefinitionof
schizophreniaremainedessentiallythesameasthatspecifiedbythe2000versionofDSM(DSMIVTR),butDSM5makesa
numberofchanges.

JohnNash,anAmerican
mathematicianandjoint
winnerofthe1994Nobel
PrizeforEconomics,who
hadschizophrenia.Hislife
wasthesubjectofthe2001
AcademyAwardwinning
filmABeautifulMind.

Subtypeclassificationssuchascatatonicandparanoidschizophreniaareremoved.Thesewereretainedinprevious
revisionslargelyforreasonsoftradition,buthadsubsequentlyprovedtobeoflittleworth.[91]
Catatoniaisnolongersostronglyassociatedwithschizophrenia.[92]
Indescribingaperson'sschizophrenia,itisrecommendedthatabetterdistinctionbemadebetweenthecurrentstateofthe
conditionanditshistoricalprogress,toachieveacleareroverallcharacterization.[91]
SpecialtreatmentofSchneider'sfirstranksymptomsisnolongerrecommended.[91]
Schizoaffectivedisorderisbetterdefinedtodemarcateitmorecleanlyfromschizophrenia.[91]
Anassessmentcoveringeightdomainsofpsychopathologysuchaswhetherhallucinationormaniaisexperiencedisrecommendedtohelpclinical
decisionmaking.[93]

TheICD10criteriaaretypicallyusedinEuropeancountries,whiletheDSMcriteriaareusedintheUnitedStatesandtovaryingdegreesaroundtheworld,and
areprevailinginresearchstudies.TheICD10criteriaputmoreemphasisonSchneiderianfirstranksymptoms.Inpractice,agreementbetweenthetwosystemsis
high.[94]
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Ifsignsofdisturbancearepresentformorethanamonthbutlessthansixmonths,thediagnosisofschizophreniformdisorderisapplied.Psychoticsymptoms
lastinglessthanamonthmaybediagnosedasbriefpsychoticdisorder,andvariousconditionsmaybeclassedaspsychoticdisordernototherwisespecified,while
schizoaffectivedisorderisdiagnosedifsymptomsofmooddisorderaresubstantiallypresentalongsidepsychoticsymptoms.Ifthepsychoticsymptomsarethe
directphysiologicalresultofageneralmedicalconditionorasubstance,thenthediagnosisisoneofapsychosissecondarytothatcondition.[90]Schizophreniais
notdiagnosedifsymptomsofpervasivedevelopmentaldisorderarepresentunlessprominentdelusionsorhallucinationsarealsopresent.[90]

Subtypes
WiththepublicationofDSM5,theAPAremovedallsubclassificationsofschizophrenia.[95]ThefivesubclassificationsincludedinDSMIVTRwere:[96][97]
Paranoidtype:Delusionsorauditoryhallucinationsarepresent,butthoughtdisorder,disorganizedbehavior,oraffectiveflatteningarenot.Delusionsare
persecutoryand/orgrandiose,butinadditiontothese,otherthemessuchasjealousy,religiosity,orsomatizationmayalsobepresent.(DSMcode295.3/ICD
codeF20.0)
Disorganizedtype:NamedhebephrenicschizophreniaintheICD.Wherethoughtdisorderandflataffectarepresenttogether.(DSMcode295.1/ICDcode
F20.1)
Catatonictype:Thesubjectmaybealmostimmobileorexhibitagitated,purposelessmovement.Symptomscanincludecatatonicstuporandwaxy
flexibility.(DSMcode295.2/ICDcodeF20.2)
Undifferentiatedtype:Psychoticsymptomsarepresentbutthecriteriaforparanoid,disorganized,orcatatonictypeshavenotbeenmet.(DSMcode
295.9/ICDcodeF20.3)
Residualtype:Wherepositivesymptomsarepresentatalowintensityonly.(DSMcode295.6/ICDcodeF20.5)
TheICD10definestwoadditionalsubtypes:[96]
Postschizophrenicdepression:Adepressiveepisodearisingintheaftermathofaschizophrenicillnesswheresomelowlevelschizophrenicsymptomsmay
stillbepresent.(ICDcodeF20.4)
Simpleschizophrenia:Insidiousandprogressivedevelopmentofprominentnegativesymptomswithnohistoryofpsychoticepisodes.(ICDcodeF20.6)
SluggishschizophreniaisintheRussianversionoftheICD10."Sluggishschizophrenia"isinthecategoryof"schizotypal"disorderinsectionF21ofchapter
V.[98]

Differentialdiagnosis
Psychoticsymptomsmaybepresentinseveralothermentaldisorders,includingbipolardisorder,[99]borderlinepersonalitydisorder,[100]drugintoxicationand
druginducedpsychosis.Delusions("nonbizarre")arealsopresentindelusionaldisorder,andsocialwithdrawalinsocialanxietydisorder,avoidantpersonality
disorderandschizotypalpersonalitydisorder.Schizotypalpersonalitydisorderhassymptomsthataresimilarbutlessseverethanthoseofschizophrenia.[5]
Schizophreniaoccursalongwithobsessivecompulsivedisorder(OCD)considerablymoreoftenthancouldbeexplainedbychance,althoughitcanbedifficultto
distinguishobsessionsthatoccurinOCDfromthedelusionsofschizophrenia.[101]Afewpeoplewithdrawingfrombenzodiazepinesexperienceasevere
withdrawalsyndromewhichmaylastalongtime.Itcanresembleschizophreniaandbemisdiagnosedassuch.[102]
Amoregeneralmedicalandneurologicalexaminationmaybeneededtoruleoutmedicalillnesseswhichmayrarelyproducepsychoticschizophrenialike
symptoms,suchasmetabolicdisturbance,systemicinfection,syphilis,HIVinfection,epilepsy,limbicencephalitis,andbrainlesions.Stroke,multiplesclerosis,
hyperthyroidism,hypothyroidismanddementiassuchasAlzheimer'sdisease,Huntington'sdisease,frontotemporaldementiaandLewyBodydementiamayalso
beassociatedwithschizophrenialikepsychoticsymptoms.[103]Itmaybenecessarytoruleoutadelirium,whichcanbedistinguishedbyvisualhallucinations,
acuteonsetandfluctuatinglevelofconsciousness,andindicatesanunderlyingmedicalillness.Investigationsarenotgenerallyrepeatedforrelapseunlessthereis
aspecificmedicalindicationorpossibleadverseeffectsfromantipsychoticmedication.Inchildrenhallucinationsmustbeseparatedfromtypicalchildhood
fantasies.[5]

Prevention
Preventionofschizophreniaisdifficultastherearenoreliablemarkersforthelaterdevelopmentofthedisorder.[104]Thereistentativeevidenceforthe
effectivenessofearlyinterventionstopreventschizophrenia.[105]Whilethereissomeevidencethatearlyinterventioninthosewithapsychoticepisodemay
improveshorttermoutcomes,thereislittlebenefitfromthesemeasuresafterfiveyears.[11]Attemptingtopreventschizophreniaintheprodromephaseisof
uncertainbenefitandthereforeasof2009isnotrecommended.[106]Cognitivebehavioraltherapymayreducetheriskofpsychosisinthoseathighriskaftera
year[107]andisrecommendedbytheNationalInstituteforHealthandCareExcellence(NICE)inthisgroup.[108]Anotherpreventativemeasureistoavoiddrugs
thathavebeenassociatedwithdevelopmentofthedisorder,includingcannabis,cocaine,andamphetamines.[8]

Management
Theprimarytreatmentofschizophreniaisantipsychoticmedications,oftenincombinationwithpsychologicalandsocialsupports.[11]Hospitalizationmayoccur
forsevereepisodeseithervoluntarilyor(ifmentalhealthlegislationallowsit)involuntarily.Longtermhospitalizationisuncommonsincedeinstitutionalization
beginninginthe1950s,althoughitstilloccurs.[10]Communitysupportservicesincludingdropincenters,visitsbymembersofacommunitymentalhealthteam,
supportedemployment[109]andsupportgroupsarecommon.Someevidenceindicatesthatregularexercisehasapositiveeffectonthephysicalandmentalhealth
ofthosewithschizophrenia.[110]

Medication
Thefirstlinepsychiatrictreatmentforschizophreniaisantipsychoticmedication,[111]whichcanreducethepositivesymptomsofpsychosisinabout7to14days.
Antipsychotics,however,failtosignificantlyimprovethenegativesymptomsandcognitivedysfunction.[30][112]Inthoseonantipsychotics,continueduse
decreasestheriskofrelapse.[113][114]Thereislittleevidenceregardingeffectsfromtheirusebeyondtwoorthreeyears.[114]
Thechoiceofwhichantipsychotictouseisbasedonbenefits,risks,andcosts.[11]Itisdebatablewhether,asaclass,typicaloratypicalantipsychoticsare
better.[9][115]Amisulpride,olanzapine,risperidoneandclozapinemaybemoreeffectivebutareassociatedwithgreatersideeffects.[116]Typicalantipsychotics
haveequaldropoutandsymptomrelapseratestoatypicalswhenusedatlowtomoderatedosages.[117]Thereisagoodresponsein4050%,apartialresponsein
3040%,andtreatmentresistance(failureofsymptomstorespondsatisfactorilyaftersixweekstotwoorthreedifferentantipsychotics)in20%ofpeople.[30]
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Clozapineisaneffectivetreatmentforthosewhorespondpoorlytootherdrugs("treatmentresistant"or"refractory"
schizophrenia),[118]butithasthepotentiallyserioussideeffectofagranulocytosis(loweredwhitebloodcellcount)inlessthan4%
ofpeople.[8][11][119]
Mostpeopleonantipsychoticshavesideeffects.Peopleontypicalantipsychoticstendtohaveahigherrateofextrapyramidalside
effectswhilesomeatypicalsareassociatedwithconsiderableweightgain,diabetesandriskofmetabolicsyndromethisismost
pronouncedwitholanzapine,whilerisperidoneandquetiapinearealsoassociatedwithweightgain.[116]Risperidonehasasimilar
rateofextrapyramidalsymptomstohaloperidol.[116]Itremainsunclearwhetherthenewerantipsychoticsreducethechancesof
developingneurolepticmalignantsyndromeortardivedyskinesia,ararebutseriousneurologicaldisorder.[120]

Risperidone(tradename
Risperdal)isacommon
atypicalantipsychotic
medication.

Forpeoplewhoareunwillingorunabletotakemedicationregularly,longactingdepotpreparationsofantipsychoticsmaybeused
toachievecontrol.[121]Theyreducetheriskofrelapsetoagreaterdegreethanoralmedications.[113]Whenusedincombination
withpsychosocialinterventionstheymayimprovelongtermadherencetotreatment.[121]TheAmericanPsychiatricAssociation
suggestsconsideringstoppingantipsychoticsinsomepeopleiftherearenosymptomsformorethanayear.[114]

Psychosocial

Anumberofpsychosocialinterventionsmaybeusefulinthetreatmentofschizophreniaincluding:familytherapy,[122]assertivecommunitytreatment,supported
employment,cognitiveremediation,[123]skillstraining,tokeneconomicinterventions,andpsychosocialinterventionsforsubstanceuseandweight
management.[124]Familytherapyoreducation,whichaddressesthewholefamilysystemofanindividual,mayreducerelapsesandhospitalizations.[122]Evidence
fortheeffectivenessofcognitivebehavioraltherapy(CBT)ineitherreducingsymptomsorpreventingrelapseisminimal.[125][126]Artordramatherapyhavenot
beenwellresearched.[127][128]Musictherapyhasbeenshowntoimprovementalstateandsocialfunctioningwhenpairedwithregularcare.[129]

Prognosis
Schizophreniahasgreathumanandeconomiccosts.[11]Itresultsinadecreasedlifeexpectancyby1025years.[14]Thisisprimarilybecauseofitsassociationwith
obesity,poordiet,sedentarylifestyles,andsmoking,withanincreasedrateofsuicideplayingalesserrole.[11][14][130]Antipsychoticmedicationsmayalsoincrease
therisk.[14]Thesedifferencesinlifeexpectancyincreasedbetweenthe1970sand1990s.[131]
Schizophreniaisamajorcauseofdisability,withactivepsychosisrankedasthethirdmostdisablingconditionafterquadriplegiaanddementiaandaheadof
paraplegiaandblindness.[132]Approximatelythreefourthsofpeoplewithschizophreniahaveongoingdisabilitywithrelapses[30]and16.7millionpeopleglobally
aredeemedtohavemoderateorseveredisabilityfromthecondition.[133]Somepeopledorecovercompletelyandothersfunctionwellinsociety.[134]Mostpeople
withschizophrenialiveindependentlywithcommunitysupport.[11]About85%areunemployed.[6]Inpeoplewithafirstepisodeofpsychosisagoodlongterm
outcomeoccursin42%,anintermediateoutcomein35%andapooroutcomein27%.[135]Outcomesforschizophreniaappearbetterinthedevelopingthanthe
developedworld.[136]Theseconclusions,however,havebeenquestioned.[137][138]
Thereisahigherthanaveragesuiciderateassociatedwithschizophrenia.Thishasbeencitedat10%,butamorerecentanalysisrevisestheestimateto4.9%,most
oftenoccurringintheperiodfollowingonsetorfirsthospitaladmission.[15][139]Severaltimesmore(20to40%)attemptsuicideatleastonce.[5][140]Therearea
varietyofriskfactors,includingmalegender,depression,andahighintelligencequotient.[140]
Schizophreniaandsmokinghaveshownastrongassociationinstudiesworldwide.[141][142]Useofcigarettesisespeciallyhighinindividualsdiagnosedwith
schizophrenia,withestimatesrangingfrom80to90%beingregularsmokers,ascomparedto20%ofthegeneralpopulation.[142]Thosewhosmoketendtosmoke
heavily,andadditionallysmokecigaretteswithhighnicotinecontent.[143]Someevidencesuggeststhatparanoidschizophreniamayhaveabetterprospectthan
othertypesofschizophreniaforindependentlivingandoccupationalfunctioning.[144]Amongpeoplewithschizophreniauseofcannabisisalsocommon.[59]

Epidemiology
Schizophreniaaffectsaround0.30.7%ofpeopleatsomepointintheirlife,[11]or24millionpeopleworldwideasof
2011.[145]Itoccurs1.4timesmorefrequentlyinmalesthanfemalesandtypicallyappearsearlierinmen[8]thepeakages
ofonsetare25yearsformalesand27yearsforfemales.[146]Onsetinchildhoodismuchrarer,[147]asisonsetinmiddleor
oldage.[148]
Despitethepriorbeliefthatschizophreniaoccursatsimilarratesworldwide,itsfrequencyvariesacrosstheworld,[5][149]
withincountries,[150]andatthelocalandneighborhoodlevel.[151]Thisvariationhasbeenestimatedtobefivefold.[6]It
causesapproximately1%ofworldwidedisabilityadjustedlifeyears[8]andresultedin20,000deathsin2010.[152]Therate
ofschizophreniavariesuptothreefolddependingonhowitisdefined.[11]
In2000,theWorldHealthOrganizationfoundthepercentageofpeopleaffectedandthenumberofnewcasesthatdevelop
eachyearisroughlysimilararoundtheworld,withagestandardizedprevalenceper100,000rangingfrom343inAfricato
544inJapanandOceaniaformenandfrom378inAfricato527inSoutheasternEuropeforwomen.[153]About1.1%of
adultshaveschizophreniaintheUnitedStates.[154]

History

Disabilityadjustedlifeyearslostdue
toschizophreniaper
100,000inhabitantsin2004.
nodata

240251

185

251262

185197

262273

197207

273284

207218

284295

218229

295

229240

Intheearly20thcentury,thepsychiatristKurtSchneiderlistedtheformsofpsychoticsymptomsthathethought
distinguishedschizophreniafromotherpsychoticdisorders.ThesearecalledfirstranksymptomsorSchneider'sfirstranksymptoms.Theyincludedelusionsof
beingcontrolledbyanexternalforcethebeliefthatthoughtsarebeinginsertedintoorwithdrawnfromone'sconsciousmindthebeliefthatone'sthoughtsare
beingbroadcasttootherpeopleandhearinghallucinatoryvoicesthatcommentonone'sthoughtsoractionsorthathaveaconversationwithotherhallucinated
voices.[155]Althoughtheyhavesignificantlycontributedtothecurrentdiagnosticcriteria,thespecificityoffirstranksymptomshasbeenquestioned.Areviewof
thediagnosticstudiesconductedbetween1970and2005foundthattheyallowneitherareconfirmationnorarejectionofSchneider'sclaims,andsuggestedthat
firstranksymptomsshouldbedeemphasizedinfuturerevisionsofdiagnosticsystems.[156]
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Thehistoryofschizophreniaiscomplexanddoesnotlenditselfeasilytoalinearnarrative.[157]Accountsofaschizophrenialikesyndromearethoughttoberare
inhistoricalrecordsbeforethe19thcentury,althoughreportsofirrational,unintelligible,oruncontrolledbehaviorwerecommon.Adetailedcasereportin1797
concerningJamesTillyMatthews,andaccountsbyPhilippePinelpublishedin1809,areoftenregardedastheearliestcasesoftheillnessinthemedicaland
psychiatricliterature.[158]TheLatinizedtermdementiapraecoxwasfirstusedbyGermanalienistHeinrichSchulein1886andthenin1891byArnoldPickina
casereportofapsychoticdisorder(hebephrenia).In1893EmilKraepelinborrowedthetermfromSchuleandPickandin1899introducedabroadnewdistinction
intheclassificationofmentaldisordersbetweendementiapraecoxandmooddisorder(termedmanicdepressionandincludingbothunipolarandbipolar
depression).[159]Kraepelinbelievedthatdementiapraecoxwasprobablycausedbyalongterm,smoulderingsystemicor"wholebody"diseaseprocessthat
affectedmanyorgansandperipheralnervesinthebodybutwhichaffectedthebrainafterpubertyinafinaldecisivecascade.[160]Hisuseoftheterm"praecox"
distinguisheditfromotherformsofdementiasuchasAlzheimer'sdiseasewhichtypicallyoccurlaterinlife.[161]Itissometimesarguedthattheuseoftheterm
dmenceprcocein1852bytheFrenchphysicianBndictMorelconstitutesthemedicaldiscoveryofschizophrenia.Howeverthisaccountignoresthefactthat
thereislittletoconnectMorel'sdescriptiveuseofthetermandtheindependentdevelopmentofthedementiapraecoxdiseaseconceptattheendofthenineteenth
century.[162]
Thewordschizophreniawhichtranslatesroughlyas"splittingofthemind"andcomesfromtheGreekrootsschizein
(,"tosplit")andphrn,phren(,,"mind")[163]wascoinedbyEugenBleulerin1908andwasintended
todescribetheseparationoffunctionbetweenpersonality,thinking,memory,andperception.AmericanandBritish
interpretationsofBeulerledtotheclaimthathedescribeditsmainsymptomsas4A's:flattenedAffect,Autism,impaired
AssociationofideasandAmbivalence.[164][165]Bleulerrealizedthattheillnesswasnotadementia,assomeofhispatients
improvedratherthandeteriorated,andthusproposedthetermschizophreniainstead.Treatmentwasrevolutionizedinthe
mid1950swiththedevelopmentandintroductionofchlorpromazine.[166]

Moleculeofchlorpromazine(trade
nameThorazine),which
revolutionizedtreatmentof
schizophreniainthe1950s

Intheearly1970s,thediagnosticcriteriaforschizophreniawerethesubjectofanumberofcontroversieswhicheventually
ledtotheoperationalcriteriausedtoday.Itbecameclearafterthe1971USUKDiagnosticStudythatschizophreniawas
diagnosedtoafargreaterextentinAmericathaninEurope.[167]ThiswaspartlyduetolooserdiagnosticcriteriaintheUS,
whichusedtheDSMIImanual,contrastingwithEuropeanditsICD9.DavidRosenhan's1972study,publishedinthe
journalScienceunderthetitle"Onbeingsaneininsaneplaces",concludedthatthediagnosisofschizophreniaintheUS
wasoftensubjectiveandunreliable.[168]Theseweresomeofthefactorsleadingtotherevisionnotonlyofthediagnosisof
schizophrenia,buttherevisionofthewholeDSMmanual,resultinginthepublicationoftheDSMIIIin1980.[169]

Thetermschizophreniaiscommonlymisunderstoodtomeanthataffectedpersonshavea"splitpersonality".Although
somepeoplediagnosedwithschizophreniamayhearvoicesandmayexperiencethevoicesasdistinctpersonalities,
schizophreniadoesnotinvolveapersonchangingamongdistinctmultiplepersonalities.TheconfusionarisesinpartduetotheliteralinterpretationofBleuler's
termschizophrenia(BleuleroriginallyassociatedSchizophreniawithdissociationandincludedsplitpersonalityinhiscategoryofSchizophrenia).[170][171]
Dissociativeidentitydisorder(havinga"splitpersonality")wasalsooftenmisdiagnosedasschizophreniabasedontheloosecriteriaintheDSMII.[171][172]The
firstknownmisuseofthetermtomean"splitpersonality"wasinanarticlebythepoetT.S.Eliotin1933.[173]Otherscholarshavetracedearlierroots.[174]Rather,
thetermmeansa"splittingofmentalfunctions",reflectingthepresentationoftheillness.[175]

Societyandculture
In2002thetermforschizophreniainJapanwaschangedfromseishinbunretsuby(,lit."mindsplitdisease")to
tgshitchsh(,lit."integrationdisorder")toreducestigma.[176]Thenewnamewasinspiredbythebiopsychosocial
modelitincreasedthepercentageofpeoplewhowereinformedofthediagnosisfrom37to70%overthreeyears.[177]Asimilar
changewasmadeinSouthKoreain2012.[178]Aprofessorofpsychiatry,JimvanOs,hasproposedchangingtheEnglishtermto
"psychosisspectrumsyndrome".[179]
IntheUnitedStates,thecostofschizophreniaincludingdirectcosts(outpatient,inpatient,drugs,andlongtermcare)andnon
healthcarecosts(lawenforcement,reducedworkplaceproductivity,andunemployment)wasestimatedtobe$62.7billionin
2002.[180]ThebookandfilmABeautifulMindchroniclesthelifeofJohnForbesNash,aNobelPrizewinningmathematicianwho
wasdiagnosedwithschizophrenia.

Violence
Individualswithseverementalillnessincludingschizophreniaareatasignificantlygreaterriskofbeingvictimsofbothviolentand
Thetermschizophreniawas
nonviolentcrime.[181]Schizophreniahasbeenassociatedwithahigherrateofviolentacts,althoughthisisprimarilyduetohigher
coinedbyEugenBleuler.
ratesofdruguse.[182]Ratesofhomicidelinkedtopsychosisaresimilartothoselinkedtosubstancemisuse,andparalleltheoverall
rateinaregion.[183]Whatroleschizophreniahasonviolenceindependentofdrugmisuseiscontroversial,butcertainaspectsofindividualhistoriesormental
statesmaybefactors.[184]
Mediacoveragerelatingtoviolentactsbyindividualswithschizophreniareinforcespublicperceptionofanassociationbetweenschizophreniaandviolence.[182]
Inalarge,representativesamplefroma1999study,12.8%ofAmericansbelievedthatindividualswithschizophreniawere"verylikely"todosomethingviolent
againstothers,and48.1%saidthattheywere"somewhatlikely"to.Over74%saidthatpeoplewithschizophreniawereeither"notveryable"or"notableatall"to
makedecisionsconcerningtheirtreatment,and70.2%saidthesameofmoneymanagementdecisions.[185]Theperceptionofindividualswithpsychosisasviolent
hasmorethandoubledinprevalencesincethe1950s,accordingtoonemetaanalysis.[186]

Researchdirections
Researchhasfoundatentativebenefitinusingminocyclinetotreatschizophrenia.[187]Nidotherapyoreffortstochangetheenvironmentofpeoplewith
schizophreniatoimprovetheirabilitytofunction,isalsobeingstudiedhowever,thereisnotenoughevidenceyettomakeconclusionsaboutitseffectiveness.[188]
Negativesymptomshaveprovenachallengetotreatastheyaregenerallynotmadebetterbymedication.Variousagentshavebeenexploredforpossiblebenefits
inthisarea.[189]Therehavebeentrialsondrugswithantiinflammatoryactivity,basedonthepremisethatinflammationmightplayaroleinthepathologyof
schizophrenia.[190]

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