SchizophreniaSchizophreniaSchizophreniaSchizophrenia

Onset 18-35 yearOnset 18-35 yearPrevalence 0.6%Prevalence 0.6%Positive, negative and disorganisation symptomsPositive, negative and disorganisation symptomsCognitive disorderCognitive disorderMultifactorial genetic and non-genetic aetiologyMultifactorial genetic and non-genetic aetiologyDevelopmental originDevelopmental origin20% life-span reduction 20% life-span reduction Cost $200 billion/year worldwideCost $200 billion/year worldwide

Dopamine Hypothesis Dopamine Hypothesis Dopamine Hypothesis Dopamine Hypothesis

Mesolimbic pathwayMesolimbic pathway

Nigrostratial pathway Nigrostratial pathway (part of EP system)(part of EP system)

Tuberoinfundibular pathwayTuberoinfundibular pathway(inhibits prolactin release)(inhibits prolactin release)

Mesocortical pathwayMesocortical pathwayHypoactivity:Hypoactivity:

negative symptomsnegative symptoms

Hyperactivity:Hyperactivity:positive symptomspositive symptoms

Haloperidol and D2 Occupancy

11C-Raclopride PET Scan

Coregistered MRI Scan

BeforeTreatment

Haloperidol2 mg/d (74% Occ.)

11C-Raclopride PET Scan

Medication side effectsMedication side effectsMedication side effectsMedication side effects

ParkinsonismParkinsonism

AcathisiaAcathisia

DystoniaDystonia

HallucinationsHallucinations

Psychological modelsPsychological modelsPsychological modelsPsychological models

Lower level Lower level intrusionsintrusions

Appraisal of Appraisal of experience as experience as

externalexternalSymptomsSymptoms

Emotional Emotional changeschanges

Cognitive Cognitive attributionsattributions

Mood and psychosisMood and psychosisMood and psychosisMood and psychosis

Disturbed source monitoringDisturbed source monitoringDisturbed source monitoringDisturbed source monitoring

Voice distorterVoice distorterFrith et al, 1995Frith et al, 1995

Auditory hallucinationsAuditory hallucinationsAuditory hallucinationsAuditory hallucinations

DelusionsDelusions

Threatning/adverse events

delusions negative self concept

Need to readjust self concept

Positive self perception at the expense of others having a negative view of the person Bentall et al., 1994 Kinderman &

Bentall, 1996

External attribution of negative events: “others are to blame for the negative things that happen to me”

actual self ideal self

Attribution self-representation cycleAttribution self-representation cycleAttribution self-representation cycleAttribution self-representation cycle

Cumulative effect of LECumulative effect of LECumulative effect of LECumulative effect of LE

OnsetOnsetPsychosisPsychosis

Hirsch et al, 1996Hirsch et al, 1996

A B

85 15 15 85

Theory of mindTheory of mindTheory of mindTheory of mind

Frith & Corcoran, 1996Frith & Corcoran, 1996Frith & Corcoran, 1996Frith & Corcoran, 1996

First order false beliefFirst order false beliefFirst order false beliefFirst order false belief

John has five cigarettes left in his packet. He John has five cigarettes left in his packet. He puts his packet on the table and goes out of puts his packet on the table and goes out of

the room. Meanwhile, Janet comes in and takes the room. Meanwhile, Janet comes in and takes one of John’s cigarettes and leaves the room one of John’s cigarettes and leaves the room

without John knowing.without John knowing.

John has five cigarettes left in his packet. He John has five cigarettes left in his packet. He puts his packet on the table and goes out of puts his packet on the table and goes out of

the room. Meanwhile, Janet comes in and takes the room. Meanwhile, Janet comes in and takes one of John’s cigarettes and leaves the room one of John’s cigarettes and leaves the room

without John knowing.without John knowing.

ToM question: When John comes back for his cigarettes, how ToM question: When John comes back for his cigarettes, how many does he think he has left?many does he think he has left?ToM question: When John comes back for his cigarettes, how ToM question: When John comes back for his cigarettes, how many does he think he has left?many does he think he has left?

Memory question: How many cigarettes are really left in Memory question: How many cigarettes are really left in John’s packet?John’s packet?Memory question: How many cigarettes are really left in Memory question: How many cigarettes are really left in John’s packet?John’s packet?

Cascade model of psychotic symptomsCascade model of psychotic symptomsCascade model of psychotic symptomsCascade model of psychotic symptoms

Jones, 1994Jones, 1994

Theory of mind Theory of mind difficultiesdifficulties

Difficulties making inferences about Difficulties making inferences about other children’s mental statesother children’s mental states

Increasingly unsure of self, Increasingly unsure of self, social withdrawalsocial withdrawal

Decreasing opportunities for social Decreasing opportunities for social interaction and reality testinginteraction and reality testing

Social isolationSocial isolation

Paranoid Paranoid attributionsattributions

CBTCBTCBTCBT

Delusions: guided discovery, socratic questioningDelusions: guided discovery, socratic questioning

Hallucinations: attributions, coping mechanismsHallucinations: attributions, coping mechanisms

Thought disorder: “thought linking”Thought disorder: “thought linking”

Negative symptoms: paced activity schedules, Negative symptoms: paced activity schedules, mastery diarymastery diary

Delusions: guided discovery, socratic questioningDelusions: guided discovery, socratic questioning

Hallucinations: attributions, coping mechanismsHallucinations: attributions, coping mechanisms

Thought disorder: “thought linking”Thought disorder: “thought linking”

Negative symptoms: paced activity schedules, Negative symptoms: paced activity schedules, mastery diarymastery diary

Prodromal phase of symptomsProdromal phase of symptomsProdromal phase of symptomsProdromal phase of symptoms

0

1

2

Years before 1st admission

Mean number of symptoms

Unspecific symptoms

Negative symptoms

Positive symptoms

Häfner et al, 1999Häfner et al, 1999

73% had prodromal symptoms73% had prodromal symptoms

onset social disabilities 2-4 onset social disabilities 2-4 years before first admissionyears before first admission

Outcome of Outcome of childhood psychotic experiencechildhood psychotic experiencessOutcome of Outcome of childhood psychotic experiencechildhood psychotic experiencess

0369

121518212427

Rate schizophre-

niform disorder age 26

age 11 NOpsychotic

experience

age 11psychotic

experience

N=761 – CIDI interviewsN=761 – CIDI interviews

Poulton et al Arch Gen Psych, 2000Poulton et al Arch Gen Psych, 2000

Transition modelTransition modelTransition modelTransition model

Psychotic Psychotic experience experience

(pre-)(pre-)

First episode First episode of disorder of disorder

(post-)(post-)

TimeTime

The process of needThe process of needThe process of needThe process of need

Psychotic experiencePsychotic experience

AttributionsAttributions

Need for careNeed for care

Emotional changeEmotional change

CopingCoping

Are voices more likely to result in need for Are voices more likely to result in need for care in the presence of delusions?care in the presence of delusions?

Are voices more likely to result in need for Are voices more likely to result in need for care in the presence of delusions?care in the presence of delusions?

VoicesVoices

No delusional No delusional ideationideation

Delusional Delusional ideationideation

SchizophreniaSchizophrenia

T1T1

T2T2

T3T3

De Clérambault, 1947; Maher & Ross, 1974De Clérambault, 1947; Maher & Ross, 1974

CannabisCannabis

No pre-existing No pre-existing psychosispsychosis

Pre-existing Pre-existing psychosispsychosis

Psychosis outcomePsychosis outcome

Interaction with pre-existing psychosisInteraction with pre-existing psychosisInteraction with pre-existing psychosisInteraction with pre-existing psychosis

T1T1

T3T3

2.2%2.2% 54.7%54.7%

American Journal of Epidemiology, 2002American Journal of Epidemiology, 2002

Lack of motivationLack of motivation

Blunting of affectBlunting of affect

Ventricular enlargementVentricular enlargementVentricular enlargementVentricular enlargement

Fetal programming and morbidity accumulationFetal programming and morbidity accumulationFetal programming and morbidity accumulationFetal programming and morbidity accumulation

Verbal learning:Verbal learning:remembering verbal informationremembering verbal information

Immediate or working memory:Immediate or working memory:keeping in mind limited informationkeeping in mind limited informationfor a short-term for a short-term

Problem solving:Problem solving:planning and sequencing actionsplanning and sequencing actions

Sustained attention:Sustained attention:target from noise discrimination over timetarget from noise discrimination over time

Cognitive ConstructsCognitive ConstructsCognitive ConstructsCognitive Constructs

Cognitive Constructs - Verbal LearningCognitive Constructs - Verbal LearningCognitive Constructs - Verbal LearningCognitive Constructs - Verbal Learning

Definition:Definition: ability to acquire, store, and retrieve verbal information for more than a few minutes ability to acquire, store, and retrieve verbal information for more than a few minutes

Example:Example: California California Verbal Learning TestVerbal Learning Test

Activities of daily living:Activities of daily living: remembering information from a remembering information from a rehabilitation program, class, vocational setting, clinic visitrehabilitation program, class, vocational setting, clinic visit

drilldrillplumsplumsvestvestparsleyparsleygrapesgrapespaprikapaprikasweatersweaterwrenchwrench

chiveschivestangerinestangerineschiselchiseljacketjacketnutmegnutmegapricotsapricotsplierspliersslacksslacks

Definition:Definition: ability to hold information “on line” in a temporary store and/or to ability to hold information “on line” in a temporary store and/or to manipulate the informationmanipulate the information

Example:Example: Letter Number Sequencing Test Letter Number Sequencing Test

Activities of daily living:Activities of daily living: carrying on a social carrying on a social conversation, switching between different tasks conversation, switching between different tasks

K3B4K3B4 _ _ _ _ _ _ _ _

R8C3G5R8C3G5 _ _ _ _ _ __ _ _ _ _ _

Cognitive Constructs – Working MemoryCognitive Constructs – Working MemoryCognitive Constructs – Working MemoryCognitive Constructs – Working Memory

Definition:Definition: ability to plan, sequence, self-monitor, comprehend, and implement rules ability to plan, sequence, self-monitor, comprehend, and implement rules

Example:Example:Wisconsin CardWisconsin CardSorting TestSorting Test

Activities of daily living:Activities of daily living: planning a meal, using planning a meal, using public transportation, following steps for a job taskpublic transportation, following steps for a job task

Cognitive Constructs – Problem SolvingCognitive Constructs – Problem SolvingCognitive Constructs – Problem SolvingCognitive Constructs – Problem Solving

100 ms

Definition:Definition: ability to respond to targets, not respond to nontargets, over a period of time ability to respond to targets, not respond to nontargets, over a period of time

Example:Example: Continuous Performance Test Continuous Performance Test

Activities of daily living:Activities of daily living: identifying relevant information identifying relevant information in a social interaction, discussions with a doctor in a social interaction, discussions with a doctor

“Press when you see a 7 preceded by a 3”

Stimulus

Response

1 second

66 55 77 44 33 77 99

hold hold hold hold hold press holdTime

Cognitive Constructs – Sustained AttentionCognitive Constructs – Sustained AttentionCognitive Constructs – Sustained AttentionCognitive Constructs – Sustained Attention

Cochrane cognitive Cochrane cognitive rehabilitationrehabilitation

Family Guidelines Family Guidelines (examples)(examples)Family Guidelines Family Guidelines (examples)(examples)

Go slowGo slow

Solve problems step-by-stepSolve problems step-by-step

Keep it simpleKeep it simple

Keep it coolKeep it cool

Give each other spaceGive each other space

Lower expectationsLower expectations

McFarlane, 2002McFarlane, 2002

Disorganised speechDisorganised speech

Pro generale continuatie en in Pro generale continuatie en in particuliere explicatie op uw particuliere explicatie op uw singuliere interrogatie onze singuliere interrogatie onze

affirmamentatie. Ontelbaarheid van affirmamentatie. Ontelbaarheid van levensverhalen zijn aan deze levensverhalen zijn aan deze bladzee gesneefd, frêle als bladzee gesneefd, frêle als

flikflokjes, zooisel van boven, als flikflokjes, zooisel van boven, als een wjoengand waaigat vol een wjoengand waaigat vol

dwaereldriften. dwaereldriften.

“One of the most elusive diseases known to man and unknown to

medicine””

Joyce, 1936Joyce, 1936

CatatoniaCatatoniaCatatoniaCatatonia

FinFin

Definition:Definition: a composite score representing memory, attention, visuospatial skills, language, etc a composite score representing memory, attention, visuospatial skills, language, etc

Example:Example: Repeatable Battery for Assessment of Neuropsychological Status Repeatable Battery for Assessment of Neuropsychological Status

Activities of daily living:Activities of daily living: large associations with most types of community large associations with most types of community adaptation including social, vocational, and rehabilitation successadaptation including social, vocational, and rehabilitation success

Brief (25-min) paper and pencil test with 2 alternate formsBrief (25-min) paper and pencil test with 2 alternate forms

Subtests:Subtests: - Immediate memory - Immediate memory - Visuospatial/constructional - Visuospatial/constructional - Language (naming and fluency)- Language (naming and fluency)- Attention- Attention- Delayed memory- Delayed memory- Total score - Total score

Summary Score From Screening TestSummary Score From Screening TestSummary Score From Screening TestSummary Score From Screening Test

PsychotherapyPsychotherapyPsychotherapyPsychotherapy

Psychological modelsPsychological modelsPsychological modelsPsychological models

Lower level Lower level intrusionsintrusions

Appraisal of Appraisal of experience as experience as

externalexternalSymptomsSymptoms

Reasoning biasesReasoning biases

Attribution biasesAttribution biases

Dysfunctional schemataDysfunctional schemata

IsolationIsolation

Adverse environmentsAdverse environments

Emotional Emotional changeschanges

Garety, Kuipers, Fowler, Garety, Kuipers, Fowler, FreemanFreeman & & Bebbington, 2001; Bebbington, 2001;

Bentall et al, 2002; Chadwick & Bentall et al, 2002; Chadwick & Birchwood, 1994; Morrison et Birchwood, 1994; Morrison et al, 1995; Hemsley et al, 1993al, 1995; Hemsley et al, 1993

CBTCBTCBTCBT Tarrier et al, 1993Tarrier et al, 1993 Drury et al, 1996Drury et al, 1996 Kuypers et al, 1997Kuypers et al, 1997 Tarrier et al, 1998Tarrier et al, 1998 Sensky et al, 2000Sensky et al, 2000 Lewis et al, 2000Lewis et al, 2000 Turkington et al, 2000Turkington et al, 2000

First episodeFirst episode

BefriendingBefriending

Supp. counsellingSupp. counselling

““Real life”Real life”

““TAU”TAU”

PsychotherapyPsychotherapyPsychotherapyPsychotherapy

Theory of mindTheory of mind

Self-monitoringSelf-monitoring

•AuditoryAuditory

•MotorMotor

•MemoryMemory

Probabilistic reasoning biasProbabilistic reasoning bias

Dysfunctional attributions/ self-esteemDysfunctional attributions/ self-esteem

Theory of mindTheory of mind

Self-monitoringSelf-monitoring

•AuditoryAuditory

•MotorMotor

•MemoryMemory

Probabilistic reasoning biasProbabilistic reasoning bias

Dysfunctional attributions/ self-esteemDysfunctional attributions/ self-esteem

Sandy en Ivan gaan samen met de trein naar Sandy en Ivan gaan samen met de trein naar huis. Sally woont in Weert maar de trein stopt huis. Sally woont in Weert maar de trein stopt niet in Weert. Sandy moet in Roermond niet in Weert. Sandy moet in Roermond uitstappen en met de bus verder gaan. Als uitstappen en met de bus verder gaan. Als Sandy eventjes weg is om een tijdschrift te Sandy eventjes weg is om een tijdschrift te kopen wordt er omgeroepen dat de trein wel in kopen wordt er omgeroepen dat de trein wel in Weert stopt. Een conducteur vertelt Ivan dat de Weert stopt. Een conducteur vertelt Ivan dat de trein wel doorgaat naar Weert en Ivan gaat trein wel doorgaat naar Weert en Ivan gaat Sandy zoeken om het nieuws te vertellen. Nog Sandy zoeken om het nieuws te vertellen. Nog voor Ivan haar gevonden heeft is ook Sandy voor Ivan haar gevonden heeft is ook Sandy reeds op de hoogte van de verandering. reeds op de hoogte van de verandering. Uiteindelijk komt Ivan haar weer tegen net nadat Uiteindelijk komt Ivan haar weer tegen net nadat ze haar ticket gekocht heeft.ze haar ticket gekocht heeft.

Vraag: voor welk station denkt Ivan dat Sandy Vraag: voor welk station denkt Ivan dat Sandy een ticket gekocht heeft?een ticket gekocht heeft?

CBTCBTCBTCBT EngagementEngagement Identiying antecedentsIdentiying antecedents Normalising rationaleNormalising rationale Diagnosing comorbid depression/anxietyDiagnosing comorbid depression/anxiety Agreement on working planAgreement on working plan

EngagementEngagement Identiying antecedentsIdentiying antecedents Normalising rationaleNormalising rationale Diagnosing comorbid depression/anxietyDiagnosing comorbid depression/anxiety Agreement on working planAgreement on working plan

The process of needThe process of needThe process of needThe process of need

Psychotic experiencePsychotic experience

AttributionsAttributions

Need for careNeed for care

Emotional changeEmotional change

The process of needThe process of needThe process of needThe process of need

Psychotic experiencePsychotic experience

Need for careNeed for care

CopingCoping

Pathways to carePathways to carePathways to carePathways to care

Filter 1Filter 1

Filter 2Filter 2

Filter 3Filter 3

Filter 4Filter 4Psychiatric hospitalPsychiatric hospital

Psychiatric out patientPsychiatric out patient

GP recognisedGP recognised

General populationGeneral population

GP practiceGP practice

Population interventionPopulation intervention

Level of riskLevel of risk

FrequencyFrequency

Population interventionPopulation interventionPopulation interventionPopulation intervention

Filter 1Filter 1

Filter 2Filter 2

Filter 3Filter 3

Filter 4Filter 4Psychiatric hospitalPsychiatric hospital

General populationGeneral population

Schizophrenia is rareSchizophrenia is rareSchizophrenia is rareSchizophrenia is rare

N=10,000N=10,000

Age 20 Age 20 yearsyears

Age 21 Age 21 yearsyears N=2N=2

Life course epidemiology of psychosisLife course epidemiology of psychosisLife course epidemiology of psychosisLife course epidemiology of psychosis

ageage22 2525

prem

orbid

leve

l

prem

orbid

leve

l

of funct

ionin

g

of funct

ionin

g

First signFirst sign

secondarysecondarypreventionprevention

TreatmentTreatment

First episodeFirst episode

1.1 year1.1 year0.9 year0.9 year

The Finnish adoption studyThe Finnish adoption studyThe Finnish adoption studyThe Finnish adoption study

Genetic riskGenetic risk

Risk adultRisk adultschizophreniaschizophrenia

Dysfunctional adoptive familyDysfunctional adoptive family

Tienari et al, 1996Tienari et al, 1996

Non-dysfuntional adoptive familyNon-dysfuntional adoptive family

Low EE

High EE

< 35 hrs.

> 35 hrs.

On med.

No med.

No med.

On med.

No med.

On med.

Total

13%13%

51%51%

69%69%

28%28%

92%92%

53%53%

42%42%

15%15%

15%15%

12%12%

N= N= 128128

Low EE = 71High EE = 57

Vaughn & Leff, 1976Vaughn & Leff, 1976