psy961: schizophrenia robyn langdon [email protected]

PSY961: SchizophreniaPSY961: SchizophreniaRobyn LangdonRobyn Langdon

[email protected]@maccs.mq.edu.au

OverviewOverview

Brief historyBrief history

Diagnostic issuesDiagnostic issues• DSM-IV criteriaDSM-IV criteria• Differential diagnosisDifferential diagnosis• ComorbidityComorbidity

EpidemiologyEpidemiology

Evidence for a biological contributionEvidence for a biological contribution• Structural Structural • Neurochemical Neurochemical

Neuropsychological impairmentsNeuropsychological impairments

Approaches to clinical heterogeneityApproaches to clinical heterogeneity

VideosVideos

Brief HistoryBrief History• From 1700’s: reports of psychotic symptoms (adopt alternate reality)From 1700’s: reports of psychotic symptoms (adopt alternate reality)• Kraepelin (1856-1926): 1Kraepelin (1856-1926): 1stst to focus on Scz as specific diagnostic entity to focus on Scz as specific diagnostic entity

– dementia praecox (progressive intellectual decline, early onset) dementia praecox (progressive intellectual decline, early onset)

• Bleuler (1857-1939): questioned “medical model” & assumption of Bleuler (1857-1939): questioned “medical model” & assumption of inevitable declineinevitable decline

– focused more on symptoms; schizophrenia (“splitting” of mental processes)focused more on symptoms; schizophrenia (“splitting” of mental processes)

• 1940’s: focus shifted to societal pressures1940’s: focus shifted to societal pressures– social labeling; schizophrenogenic mother; double-bind situations social labeling; schizophrenogenic mother; double-bind situations

• 1950’s: Schneider (1950’s): 11950’s: Schneider (1950’s): 1stst-rank markers of Scz-rank markers of Scz– auditory hallucinations; loss of boundary experiences & delusions of perception auditory hallucinations; loss of boundary experiences & delusions of perception

(known today as ideas of reference)(known today as ideas of reference)– all positive (+ve) symptoms all positive (+ve) symptoms

• Andreasen: -ve features as important as, if not more than, +ve featuresAndreasen: -ve features as important as, if not more than, +ve features– +ve symptoms (delusions, hallucinations) +ve symptoms (delusions, hallucinations) abnormal by presenceabnormal by presence– -ve symptoms (apathy, anhedonia) -ve symptoms (apathy, anhedonia) abnormal by absenceabnormal by absence

• On-going debate concerning whether Scz a disease or a syndromeOn-going debate concerning whether Scz a disease or a syndrome– http://www.schizophreniaforum.org/http://www.schizophreniaforum.org/

Current DSMIV criteriaCurrent DSMIV criteriaA) 2 or > characteristic sxs for 1 month (now include –ve sxs)A) 2 or > characteristic sxs for 1 month (now include –ve sxs)• delusionsdelusions (false beliefs)(false beliefs)

– based on incorrect inference (?), firmly sustained despite what others based on incorrect inference (?), firmly sustained despite what others believe & evidence to contrary (?), not accepted by othersbelieve & evidence to contrary (?), not accepted by others

– vary in scope (widespread vs. circumscribed)vary in scope (widespread vs. circumscribed)– vary in intensity (held with some doubt – extreme conviction & influence vary in intensity (held with some doubt – extreme conviction & influence

behaviour)behaviour)• intensity fluctuatesintensity fluctuates

– ““ordinary” vs. “bizarre”ordinary” vs. “bizarre”– range of common delusional themesrange of common delusional themes

• persecutionpersecution• delusions of reference (contrast with ideas of reference)delusions of reference (contrast with ideas of reference)• religious/spiritualreligious/spiritual• grandiosegrandiose• somaticsomatic• loss of boundary loss of boundary



• hallucinations (false percepts)hallucinations (false percepts)– sensory experiences with same sense of reality as percepts but without sensory experiences with same sense of reality as percepts but without

exogenous stimulation of senses (distinct from illusions, exclude exogenous stimulation of senses (distinct from illusions, exclude hypnogogic & hypnopompic experiences)hypnogogic & hypnopompic experiences)

– auditoryauditory • noises, bumps, musicnoises, bumps, music• auditory verbal hallucinations (voices)auditory verbal hallucinations (voices)

– commenting (2commenting (2ndnd person) person)– conversing (3conversing (3rdrd person) person)

– visualvisual– somaticsomatic– olfactoryolfactory– gustatory (taste)gustatory (taste)




exogenous stimulation of senses (not illusions)exogenous stimulation of senses (not illusions)• disorganized speech (positive or formal thought disorder)disorganized speech (positive or formal thought disorder)

– characterized by derailed, tangential, incoherent speechcharacterized by derailed, tangential, incoherent speech

Examples of disorganized speechExamples of disorganized speech DerailmentDerailmentQ. “How are things at home?”Q. “How are things at home?”A. “My mother is too ill. No money. It all comes out of her pocket. My flat’s A. “My mother is too ill. No money. It all comes out of her pocket. My flat’s

leaking. It’s ruined my mattress. It’s in Lambeth council. I’d like to know what leaking. It’s ruined my mattress. It’s in Lambeth council. I’d like to know what the caption in the motto under their coat of arms is. It’s in Latin …..”the caption in the motto under their coat of arms is. It’s in Latin …..”

TangentialityTangentialityQ. “What city are you from?”Q. “What city are you from?”A. “… I was born in Iowa, but I know that I’m white instead of black so apparently I A. “… I was born in Iowa, but I know that I’m white instead of black so apparently I

came from the north somewhere and I don’t know where, you know, I really came from the north somewhere and I don’t know where, you know, I really don’t know where my ancestors came from …. “don’t know where my ancestors came from …. “

IllogicalityIllogicalityQ. “Are parents important in society?Q. “Are parents important in society?A. “Parents are the people that raise you. Anything that raises you can be a A. “Parents are the people that raise you. Anything that raises you can be a

parent. Parents can be anything – material, vegetable or mineral – that has parent. Parents can be anything – material, vegetable or mineral – that has taught you something. Rocks – a person can look at a rock and learn taught you something. Rocks – a person can look at a rock and learn something from it, so that would be a parent.”something from it, so that would be a parent.”




exogenous stimulation of senses (not illusions)exogenous stimulation of senses (not illusions)• disorganized speech (thought disorder)disorganized speech (thought disorder)

– characterized by derailed, tangential, incoherent speechcharacterized by derailed, tangential, incoherent speech• disorganized or catatonic behaviourdisorganized or catatonic behaviour

– inappropriate or bizarre behaviour, withdrawal from responding to inappropriate or bizarre behaviour, withdrawal from responding to environment (stupor, mutism, rigidity & posturing, repetitive behaviour)environment (stupor, mutism, rigidity & posturing, repetitive behaviour)







• negative symptomsnegative symptoms– flat affect, thought blocking, apathy, anhedoniaflat affect, thought blocking, apathy, anhedonia








** Only one symptom if delusions bizarre or hearing voices (Schneider influence)** Only one symptom if delusions bizarre or hearing voices (Schneider influence)

** NO core symptom(s)** NO core symptom(s)








** Only one symptom if delusions bizarre or hearing voices (Schneider influence)** Only one symptom if delusions bizarre or hearing voices (Schneider influence)** NO core symptom(s)** NO core symptom(s)

B) Social, personal, occupational dysfunctionB) Social, personal, occupational dysfunctionC) Overall duration 6 months (at least 1 month Criterion A sxs)C) Overall duration 6 months (at least 1 month Criterion A sxs)

Differential DiagnosisDifferential Diagnosis

““Easy” basket: Psychotic sxs present but differentiated from Scz Easy” basket: Psychotic sxs present but differentiated from Scz by (a) identifiable cause or (b) time-frameby (a) identifiable cause or (b) time-frame

• a.1 Psychotic disorder due to medical condition (a.1 Psychotic disorder due to medical condition (“organic psychosis”“organic psychosis”))– CNS disorders (Huntington’s, Parkinson’s)CNS disorders (Huntington’s, Parkinson’s)– CNS infections (encephalitis, syphilis)CNS infections (encephalitis, syphilis)– metabolic disorders (hypercalcemia) metabolic disorders (hypercalcemia) – myelin diseases (MS)myelin diseases (MS)– DementiasDementias– epilepsy, tumours, closed head injuryepilepsy, tumours, closed head injury

• a.2 Substance induced psychotic disordera.2 Substance induced psychotic disorder– toxins (e.g. heavy metals)toxins (e.g. heavy metals)– drugsdrugs

• medicationsmedications• street drugs (substance abuse common, abstinence desirable during street drugs (substance abuse common, abstinence desirable during

observation, clues from types of sxs - e.g. cannabis observation, clues from types of sxs - e.g. cannabis paranoia, paranoia, methampthetamine or ice methampthetamine or ice aggression & violence) aggression & violence)

• b.1 Brief psychotic disorderb.1 Brief psychotic disorder• b.2 Schizophreniform disorderb.2 Schizophreniform disorder


““Not so easy” basketNot so easy” basket1.1. Delusional disorderDelusional disorder

– characterized by “non-bizarre” delusionscharacterized by “non-bizarre” delusions• erotomania (e.g. loved by a famous person, Elle)erotomania (e.g. loved by a famous person, Elle)• delusional jealousy (loved one is unfaithful)delusional jealousy (loved one is unfaithful)• paranoia (neighbours are plotting against one)paranoia (neighbours are plotting against one)

– auditory & visual hallucinations are not prominentauditory & visual hallucinations are not prominent• tactile & olfactory hallucinations may be present if part of delusiontactile & olfactory hallucinations may be present if part of delusion

– no marked –ve sxsno marked –ve sxs– psychosocial function not impaired (unless direct result of delusion)psychosocial function not impaired (unless direct result of delusion)

2.2. Personality disordersPersonality disorders– long-standing patterns of interpreting world (present early adolescence)long-standing patterns of interpreting world (present early adolescence)

• no frank psychotic symptomsno frank psychotic symptoms

ButBut paranoidparanoid, , schizoidschizoid & & schizotypalschizotypal sxs part of Scz prodrome sxs part of Scz prodrome – Paranoid PDParanoid PD: persistent suspicion, feelings of threat, holds grudges: persistent suspicion, feelings of threat, holds grudges– Schizoid PDSchizoid PD: withdrawn, aloof, constricted affect (distant) : withdrawn, aloof, constricted affect (distant) – Schizotypal PDSchizotypal PD: ideas of reference, magical thinking, suspiciousness, odd speech : ideas of reference, magical thinking, suspiciousness, odd speech

& behaviour, constricted affect, poor relationships & behaviour, constricted affect, poor relationships


3. 3. Mood disorder with psychotic featuresMood disorder with psychotic features

4. Schizoaffective disorder4. Schizoaffective disorderMood disorder with psychotic features, Schizoaffective Disorder & Scz Mood disorder with psychotic features, Schizoaffective Disorder & Scz are all part of schizophrenia spectrumare all part of schizophrenia spectrumQ’s you need to be asking are:Q’s you need to be asking are:

– How independent are mood & psychotic symptoms?How independent are mood & psychotic symptoms?– Does each type of symptom appear independently of the other? Does each type of symptom appear independently of the other? – If psychotic sxs If psychotic sxs onlyonly arisearise in context of mood episode in context of mood episode

Mood disorder with psychotic featuresMood disorder with psychotic features– nihilistic & hypochondrial delusions arise in context of depression nihilistic & hypochondrial delusions arise in context of depression – grandiose delusions arise in context of manic episodegrandiose delusions arise in context of manic episode

– If both types of symptoms prominent & If both types of symptoms prominent & occur independentlyoccur independently of each other of each other Schizoaffective DisorderSchizoaffective Disorder

But these can be difficult judgmentsBut these can be difficult judgments– Ask about 1Ask about 1stst episode: were mood symptoms prominent then? episode: were mood symptoms prominent then?– Be cautious: secondary depression is common in SczBe cautious: secondary depression is common in Scz

ComorbidityComorbidityApprox 50% PwScz, at least one comorbid psychiatric or medical Approx 50% PwScz, at least one comorbid psychiatric or medical

condition (Green, Canuso, Brenner & Wojcik, 2003)condition (Green, Canuso, Brenner & Wojcik, 2003)• Depression, most common psychiatric comorbidityDepression, most common psychiatric comorbidity

– associated with suicideassociated with suicide• earlier studies estimated lifetime suicide rate 0f 10%earlier studies estimated lifetime suicide rate 0f 10%• Palmer, Pankratz & Bostwick (2005) meta-analysis of studies observing PwScz Palmer, Pankratz & Bostwick (2005) meta-analysis of studies observing PwScz

for at least 2 yrs for at least 2 yrs 4.9% suicide rate (usually near illness onset) 4.9% suicide rate (usually near illness onset)• Anxiety disorders (eg OCD) also present & complicate treatmentAnxiety disorders (eg OCD) also present & complicate treatment• Recent focus onRecent focus on cannabis abuse cannabis abuse

– prevalence studies (e.g. Ferdinand et al., 2005)prevalence studies (e.g. Ferdinand et al., 2005)• psychotic sxs present psychotic sxs present OR 1.7 cannabis use present OR 1.7 cannabis use present• cannabis use present cannabis use present OR 2.8 psychosis present OR 2.8 psychosis present

– longitudinal studies (e.g. Arseneault et al., 2002)longitudinal studies (e.g. Arseneault et al., 2002)• cannabis use by 15 yrs age cannabis use by 15 yrs age 3.5 risk of developing psychosis 3.5 risk of developing psychosis

– interaction with specific genotype (Caspi et al., 2005) interaction with specific genotype (Caspi et al., 2005)

• Comorbid medical conditions also important (e.g. Comorbid medical conditions also important (e.g. diabetesdiabetes))

CannabisCannabis

SczSczGenetic liabilityGenetic liability

?

Brief note on medication side effectsBrief note on medication side effectsNeuroleptic Malignant SyndromeNeuroleptic Malignant Syndrome (rare toxic reaction to antipsychotics) (rare toxic reaction to antipsychotics)• rigid muscles, fever, confusion or coma, sweating, increased heart raterigid muscles, fever, confusion or coma, sweating, increased heart rate

Tardive DyskinesiaTardive Dyskinesia• involuntary movements of tongue, mouth, jaw (sucking, chewing) & involuntary movements of tongue, mouth, jaw (sucking, chewing) &

extremities, can be jerky, purposeless or rhythmic movements of arms & extremities, can be jerky, purposeless or rhythmic movements of arms & legslegs

AkathisiaAkathisia• subjective experience of restlessness with fidgeting, pacing, rockingsubjective experience of restlessness with fidgeting, pacing, rocking

Other motor disturbancesOther motor disturbances• stiffness & reduced spontaneity of movement, slurring, abnormal posturing stiffness & reduced spontaneity of movement, slurring, abnormal posturing

& grimacing& grimacing

ClozapineClozapine (used when patient drug-resistant) can cause: (used when patient drug-resistant) can cause:• Agranulocytosis Agranulocytosis (lack of white blood cells)(lack of white blood cells)• fluid retentionfluid retention

Other problemsOther problems• dry mouth, constipation, blurred vision, decreased sex drive, drowsiness, dry mouth, constipation, blurred vision, decreased sex drive, drowsiness,

weight gainweight gain

Further evidence of heterogeneity: Further evidence of heterogeneity: Onset & prognosisOnset & prognosis

Onset can be acute (1 week) or insidious (> 6 months)Onset can be acute (1 week) or insidious (> 6 months)Current focus on early psychosis intervention:Current focus on early psychosis intervention:• Important to identify prodromeImportant to identify prodrome

– Phases: Prodrome, Acute & ResidualPhases: Prodrome, Acute & Residual– 3 types high-risk (prodrome) individuals (Yung, McGorry & colleagues)3 types high-risk (prodrome) individuals (Yung, McGorry & colleagues)

1.1. brief time-limited frank psychotic symptomsbrief time-limited frank psychotic symptoms2.2. attenuated sxs (e.g. suspiciousness, confused thought & speech)attenuated sxs (e.g. suspiciousness, confused thought & speech)3.3. genetic high-risk (look at family history) & drop in functiongenetic high-risk (look at family history) & drop in function

Course of illness variable: Course of illness variable: • Torrey (1988)Torrey (1988)

– 25% 25% recoveredrecovered (?) (?),, 25% independent 25% independent,, 4040% community support% community support, , 10% suicide10% suicide • Robinson et al. (2004)Robinson et al. (2004) focusfocuseded on s on sxsxs & socio-occupational functioning & socio-occupational functioning

– delusions </= 2 delusions </= 2 ((SAPSSAPS)) & negative sxs </= 3 & negative sxs </= 3 ((SANSSANS))– living living day-to-day without supervisionday-to-day without supervision & social & social interactions > interactions > once a once a weekweek– meet criteria for 2 yrs meet criteria for 2 yrs

• 47.2% achieved symptom remission47.2% achieved symptom remission• 25.5% adequate social functioning 25.5% adequate social functioning • onlyonly 13.7%13.7% met full recovery criteria met full recovery criteria

EpidemiologyEpidemiologyRefer Refer http://www.qscr.uq.edu.au & &

http://www.qcmhr.uq.edu.au/epi/Lifetime prevalence approx. 1% (Lifetime prevalence approx. 1% (“roughly similar”“roughly similar” across across

world)world)• higher incidence rates in migrants, developed countries, urban higher incidence rates in migrants, developed countries, urban

communities communities • colder the climate, greater the risk (latitude effects)colder the climate, greater the risk (latitude effects)

Onset is variable Onset is variable • typical onset late adolescence to mid-20’s (median 19 years: Rey, 1992)typical onset late adolescence to mid-20’s (median 19 years: Rey, 1992)

0

20

40

60

80

100

120

16-25 26-35 36-45 46-55 56-65 66-75 75+

MALES

FEMALES

http://www.qscr.uq.edu.au/

http://www.qcmhr.uq.edu.au/epi/

EpidemiologyEpidemiology

Sex differencesSex differences•• traditional wisdom: prevalencetraditional wisdom: prevalence is is “roughly equally”“roughly equally” in men & womenin men & women

– QCSR study: median ratio of males to females is 1.4QCSR study: median ratio of males to females is 1.4

•• childhood onset Scz more common in maleschildhood onset Scz more common in males

•• amongst 17-18 yr olds, 4 males to 1 femaleamongst 17-18 yr olds, 4 males to 1 female

•• later age of onset in females (later age of onset in females (33--5 yrs 5 yrs older older on averageon average))• symptoms & prognosis generally worse for malessymptoms & prognosis generally worse for males

– less responsive to antipsychotics, higher relapse, poorer long-term less responsive to antipsychotics, higher relapse, poorer long-term adjustment (social life, marriage, work, functioning, suicide)adjustment (social life, marriage, work, functioning, suicide)

• women show menstrual fluctuations in symptom severitywomen show menstrual fluctuations in symptom severity

Possible implications of sex differencesPossible implications of sex differences• different hormonal activity at puberty?different hormonal activity at puberty?• estrogen protection hypothesis?estrogen protection hypothesis?

– second peak in onset after menopausesecond peak in onset after menopause– premenstrual exacerbation of sxs (low estrogen levels)premenstrual exacerbation of sxs (low estrogen levels)

Evidence for biological contributionEvidence for biological contribution

Genetic vulnerabilityGenetic vulnerability

Adoptee studies rule out strong role for shared environmentAdoptee studies rule out strong role for shared environment• biological rather than adoptive relatives determine riskbiological rather than adoptive relatives determine risk

0 10 20 30 40 50

POPULATIONPOPULATIONCOUSINCOUSIN

UNCLEUNCLE/AUNTAUNTNEPHEWNEPHEW

GRANDCHILDGRANDCHILDHALFHALF SIBPARENTPARENT

FULL SIBFULL SIB

CHILD - 1 PARENTCHILD - 1 PARENTDZ TWINDZ TWIN

CHILD - 2 PARENTSCHILD - 2 PARENTS

MZ TWINMZ TWIN

Environmental risk factorsEnvironmental risk factors• Pregnancy complications (Jones & Cannon, 1998)Pregnancy complications (Jones & Cannon, 1998)

• Viral hypothesisViral hypothesis– PwScz more likely to be born in winterPwScz more likely to be born in winter– incidence of Scz higher in generations born during flu epidemicsincidence of Scz higher in generations born during flu epidemics

• Paternal age (Zammit et al., 2003)Paternal age (Zammit et al., 2003) – risk of Scz increases in “dose-dependent” way with increasingrisk of Scz increases in “dose-dependent” way with increasing paternal age paternal age

– 1.3 OR increase for each 10-yr increase in father’s age1.3 OR increase for each 10-yr increase in father’s age

• Urban riskUrban risk– role of pollution or maternal stressrole of pollution or maternal stress

• Incidence higher in migrants (Sharpley et al., 2001)Incidence higher in migrants (Sharpley et al., 2001)

Relative riskRelative risk

PreeclampsiaPreeclampsia 99

Perinatal brain damagePerinatal brain damage 77

11stst trimester under-nutrition trimester under-nutrition 22

22ndnd trimester maternal flu trimester maternal flu 22

General conception

Genetic Liability

Environmental factors

Neurodevelopmental changes(early & late)

Brain dysfunction

vviriral & al & pregnancy complicationspregnancy complications

urban riskurban risk

synapticsynaptic pruningpruningabnormal abnormal D activityD activity

Brain dysfunction: structural changesBrain dysfunction: structural changes

Postmortem evidence Postmortem evidence • brains of brains of PwScz PwScz 6% lighter6% lighter• enlarged enlarged ventriclesventricles• smaller temporosmaller temporolimbic limbic regionsregions (hippocampus & amygdala) (hippocampus & amygdala) with with

abnormal neuronal structureabnormal neuronal structure• frontal frontal & temporal (& temporal (rather than generalrather than general)) atrophy atrophy

– prominent sulciprominent sulci (Gyrification Index) (Gyrification Index)

In vivo sIn vivo structural imagingtructural imaging ( (MRI)MRI)• enlarged ventriclesenlarged ventricles• ddecreased cortical volumeecreased cortical volume

– frontal lobesfrontal lobes & temporolimbic regions ( & temporolimbic regions (hippocampus, amygdala, basal hippocampus, amygdala, basal gangliaganglia, , thalamusthalamus

– more specific details: Pantelis et al. (2003)more specific details: Pantelis et al. (2003)

Functional imaging (fMRI) findings similarFunctional imaging (fMRI) findings similarStructural changes (frontal) generally associated with –ve sxs, Structural changes (frontal) generally associated with –ve sxs,

less consistent associations with +ve sxsless consistent associations with +ve sxs

Brain dysfunction: neurochemical Brain dysfunction: neurochemical abnormalitiesabnormalities

Dopamine Dopamine (D) (D) hyperhyperactivity hypothesisactivity hypothesis• D D agonists (amphetamines) induce psychotic sagonists (amphetamines) induce psychotic sxsxs (paranoia) (paranoia)• antipsychotics block antipsychotics block D D receptors or receptors or D D releaserelease• postmortem studiespostmortem studies report report increased increased D D receptors in limbic receptors in limbic regionsregions

– may explain age of onset (increased may explain age of onset (increased D D activityactivity in late adolescence in late adolescence) & role ) & role of stress in of stress in relapse relapse (stress may induce (stress may induce D D metabolism)metabolism)

But But it’s it’s not that straightforwardnot that straightforward• effecteffectss of antipsychotics not immediate of antipsychotics not immediate• D D hhyperyperactivity in subcortactivity in subcortical regions, but D ical regions, but D hypohypoactivity in prefrontal activity in prefrontal

cortexcortex• different modelsdifferent models::

– ddifferent symptoms ifferent symptoms reflect reflect different pathological processesdifferent pathological processes (Crow) (Crow) – iinteracnteraction of different D tion of different D systems (systems (disruption of regulatory feedback loops: disruption of regulatory feedback loops:

WeinbergerWeinberger))– other other neurotransmitters neurotransmitters may be more may be more critical critical (glutamate & NMDA)(glutamate & NMDA)

• PCP (angel dust) induces loss of boundary experiencesPCP (angel dust) induces loss of boundary experiences• PCP blocks glutamate receptorsPCP blocks glutamate receptors


NeuroNeuropsychological profile psychological profile generally consistent with generally consistent with neuroanatomical findingsneuroanatomical findings (i.e. temporolimbic & frontal deficits) (i.e. temporolimbic & frontal deficits)

• MemoryMemory– verbal: learning over trialsverbal: learning over trials– nonverbal: more variabilitynonverbal: more variability

• Executive functionExecutive function– set-shifting (set-shifting (WCSTWCST))– planning (planning (Tower of LondonTower of London))– inhibitory control (Stroop, Hayling Sentence Completion)inhibitory control (Stroop, Hayling Sentence Completion)

• Sustained AttentionSustained Attention – CPCPTT

• SSocial cognitionocial cognition– emotion recognition (amygdala)emotion recognition (amygdala)

• may be specific to processing of threat signalsmay be specific to processing of threat signals– theory of mind (mPFC)theory of mind (mPFC)


Mental (theory-of-mind) Non-mental Control


00.20.40.60.8

11.21.41.61.8

2

Mental Non-mental

EP Pats

Conts


Don’t assume too much of clientsDon’t assume too much of clients• poor sustained attentionpoor sustained attention• distractibledistractible• memory problemsmemory problems

– may not follow complex argumentsmay not follow complex arguments

• miss social cuesmiss social cues• fail to appreciate other people’s perspectivesfail to appreciate other people’s perspectives• misinterpret abstract or indirect comments (e.g. jokes, misinterpret abstract or indirect comments (e.g. jokes,

sarcasm)sarcasm)• lack of insight is commonlack of insight is common

Clinical heterogeneityClinical heterogeneity

Patients are individualsPatients are individualsNeuroanatomical & neurospychological findings based on Neuroanatomical & neurospychological findings based on meanmean

differencesdifferences• group differences group differences quantitativequantitative rather than rather than qualitativequalitative• lots of overlap & considerable individual variabilitylots of overlap & considerable individual variability

How do we conceptualise clinical heterogeneity of Scz?How do we conceptualise clinical heterogeneity of Scz?• different subtypes of Scz patientsdifferent subtypes of Scz patients

– paranoid vs. disorganized vs. catatonic vs. undifferentiatedparanoid vs. disorganized vs. catatonic vs. undifferentiated– deficit vs. non-deficit Sczdeficit vs. non-deficit Scz– core vs. non-core Scz core vs. non-core Scz

• But But – patients don’t fit neatly into subtypespatients don’t fit neatly into subtypes– subtypes are not stable: sxs change over timesubtypes are not stable: sxs change over time


Syndrome approachSyndrome approach• don’t subtype patients, subtype clinical sxsdon’t subtype patients, subtype clinical sxs• different clinical syndromes occur independentlydifferent clinical syndromes occur independently1.1. Crow’s dichotomyCrow’s dichotomy

– Type I syndromeType I syndrome: positive sxs, responsive to neuroleptic medication, : positive sxs, responsive to neuroleptic medication, caused by neurotransmitter deregulationcaused by neurotransmitter deregulation

– Type II syndromeType II syndrome: negative sxs, associated with general cognitive deficits, : negative sxs, associated with general cognitive deficits, caused by structural brain abnormalitiescaused by structural brain abnormalities

2.2. empirical studies (PCA analysis) empirical studies (PCA analysis) at least 3 major (relatively at least 3 major (relatively independent) syndromesindependent) syndromes

– Reality distortionReality distortion– Disorganization Disorganization – Negative symptomsNegative symptoms

But empirical solutions only as good as measures usedBut empirical solutions only as good as measures used


Cognitive neuropsychological approachCognitive neuropsychological approach• focus on focus on specific sxs specific sxs (e.g. delusions or hallucinations)(e.g. delusions or hallucinations)1.1. DelusionsDelusions

– Maher (1974, 1988): Maher (1974, 1988): abnormal experiences explain abnormal abnormal experiences explain abnormal beliefsbeliefs

– Langdon & Coltheart (2000) 2-factor frameworkLangdon & Coltheart (2000) 2-factor framework• abnormal experience not sufficientabnormal experience not sufficient• Factor 1 processes lead to abnormal experiences that explain Factor 1 processes lead to abnormal experiences that explain

specific specific contentcontent of delusion of delusion • Factor 2 processes explain Factor 2 processes explain adoption/persistenceadoption/persistence of delusion of delusion

– JTC biasJTC bias– Externalising biasExternalising bias– Social cognition deficitsSocial cognition deficits


Cognitive neuropsychological approachCognitive neuropsychological approach2.2. Auditory verbal hallucinationsAuditory verbal hallucinations

• Frith & colleagues: impaired monitoring of inner speechFrith & colleagues: impaired monitoring of inner speech• Nayani & David: involuntary auditory memoriesNayani & David: involuntary auditory memories• Badcock, Walters & colleagues: source monitoring problem + Badcock, Walters & colleagues: source monitoring problem +

inhibitory deficit inhibitory deficit

3.3. Thought disorderThought disorder• Rossell: Semantic deficitsRossell: Semantic deficits• Langdon; Sarfati: Theory of mind problems Langdon; Sarfati: Theory of mind problems

psy961: schizophrenia robyn langdon [email protected]

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ve featuresandreasen

presence ve symptoms

symptoms schizophrenia

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hallucinations abnormal

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characteristic sxs

current dsmiv criteria