PSY961: Schizophrenia

Robyn Langdon [email protected]

Overview Brief history Diagnostic issues

• DSM-IV criteria • Differential diagnosis • Comorbidity

Epidemiology Evidence for a biological contribution

• Structural • Neurochemical

Neuropsychological impairments Approaches to clinical heterogeneity Videos

Brief History

• From 1700’s: reports of psychotic symptoms (adopt alternate reality) • Kraepelin (1856-1926): 1 st to focus on Scz as specific diagnostic entity – dementia praecox (progressive intellectual decline, early onset) • Bleuler (1857-1939): questioned “medical model” & assumption of inevitable decline – focused more on symptoms; schizophrenia (“splitting” of mental processes) • 1940’s: focus shifted to societal pressures – social labeling; schizophrenogenic mother; double-bind situations • 1950’s: Schneider (1950’s): 1 st -rank markers of Scz – auditory hallucinations; loss of boundary experiences & delusions of perception (known today as ideas of reference) – all positive (+ve) symptoms • Andreasen: -ve features as important as, if not more than, +ve features – +ve symptoms (delusions, hallucinations)

abnormal by presence

– -ve symptoms (apathy, anhedonia)

abnormal by absence

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

Current DSMIV criteria

• A) 2 or > characteristic sxs for 1 month (now include –ve sxs)

delusions (false beliefs)

– based on incorrect inference (?), firmly sustained despite what others believe & evidence to contrary (?), not accepted by others – vary in scope (widespread vs. circumscribed) – vary in intensity (held with some doubt – extreme conviction & influence behaviour) • intensity fluctuates – “ordinary” vs. “bizarre” – range of common delusional themes • persecution • delusions of reference (contrast with ideas of reference) • religious/spiritual • grandiose • somatic • loss of boundary

Current DSMIV criteria

• • A) 2 or > characteristic sxs for 1 month (now include –ve sxs)

delusions (false beliefs)

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

hallucinations (false percepts)

– sensory experiences with same sense of reality as percepts but without exogenous stimulation of senses (distinct from illusions, exclude hypnogogic & hypnopompic experiences) – auditory • noises, bumps, music • auditory verbal hallucinations (voices) – commenting (2 nd person) – conversing (3 rd person) – visual – somatic – olfactory – gustatory (taste)

Current DSMIV criteria

• • • A) 2 or > characteristic sxs for 1 month (now include –ve sxs)

delusions (false beliefs)

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

hallucinations (false percepts)

– sensory experiences with same sense of reality as percepts but without exogenous stimulation of senses (not illusions)

disorganized speech (positive or formal thought disorder)

– characterized by derailed, tangential, incoherent speech

Examples of disorganized speech

Derailment Q. “How are things at home?” 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 the caption in the motto under their coat of arms is. It’s in Latin …..” Tangentiality 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 came from the north somewhere and I don’t know where, you know, I really don’t know where my ancestors came from …. “ Illogicality Q. “Are parents important in society?

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 taught you something. Rocks – a person can look at a rock and learn something from it, so that would be a parent.”

Current DSMIV criteria

• • • • A) 2 or > characteristic sxs for 1 month (now include –ve sxs)

delusions (false beliefs)

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

hallucinations (false percepts)

– sensory experiences with same sense of reality as percepts but without exogenous stimulation of senses (not illusions)

disorganized speech (thought disorder)

– characterized by derailed, tangential, incoherent speech

disorganized or catatonic behaviour

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

Current DSMIV criteria

• • • • • A) 2 or > characteristic sxs for 1 month (now include –ve sxs)

delusions (false beliefs)

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

hallucinations (false percepts)

– sensory experiences with same sense of reality as percepts but without exogenous stimulation of senses (not illusions)

disorganized speech (thought disorder)

– characterized by derailed, tangential, incoherent speech

disorganized or catatonic behaviour

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

negative symptoms

– flat affect, thought blocking, apathy, anhedonia

Current DSMIV criteria

• • • • • A) 2 or > characteristic sxs for 1 month (now include –ve sxs)

delusions (false beliefs)

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

hallucinations (false percepts)

– sensory experiences with same sense of reality as percepts but without exogenous stimulation of senses (not illusions)

disorganized speech (thought disorder)

– characterized by derailed, tangential, incoherent speech

disorganized or catatonic behaviour

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

negative symptoms

– flat affect, thought blocking, apathy, anhedonia

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

Current DSMIV criteria

• • • • • A) 2 or > characteristic sxs for 1 month (now include –ve sxs)

delusions (false beliefs)

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

hallucinations (false percepts)

– sensory experiences with same sense of reality as percepts but without exogenous stimulation of senses (not illusions)

disorganized speech (thought disorder)

– characterized by derailed, tangential, incoherent speech

disorganized or catatonic behaviour

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

negative symptoms

– flat affect, thought blocking, apathy, anhedonia

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

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

Differential Diagnosis

“Easy” basket: Psychotic sxs present but differentiated from Scz by (a) identifiable cause or (b) time-frame • a.1 Psychotic disorder due to medical condition (

“organic psychosis”

) – CNS disorders (Huntington’s, Parkinson’s) – CNS infections (encephalitis, syphilis) – metabolic disorders (hypercalcemia) – myelin diseases (MS) – Dementias – epilepsy, tumours, closed head injury • a.2 Substance induced psychotic disorder – toxins (e.g. heavy metals) – drugs • medications • street drugs (substance abuse common, abstinence desirable during observation, clues from types of sxs - e.g. cannabis  paranoia, methampthetamine or ice  aggression & violence) • b.1 Brief psychotic disorder • b.2 Schizophreniform disorder

Differential Diagnosis

“Not so easy” basket 1. Delusional disorder – characterized by “non-bizarre” delusions • • • erotomania (e.g. loved by a famous person, Elle) delusional jealousy (loved one is unfaithful) paranoia (neighbours are plotting against one) – – – auditory & visual hallucinations are not prominent • tactile & olfactory hallucinations may be present if part of delusion no marked –ve sxs psychosocial function not impaired (unless direct result of delusion) 2. Personality disorders – long-standing patterns of interpreting world (present early adolescence) • no frank psychotic symptoms

But paranoid

,

schizoid

– – – &

schizotypal

sxs part of Scz prodrome Paranoid PD : persistent suspicion, feelings of threat, holds grudges Schizoid PD : withdrawn, aloof, constricted affect (distant) Schizotypal PD : ideas of reference, magical thinking, suspiciousness, odd speech & behaviour, constricted affect, poor relationships

Differential Diagnosis 3. Mood disorder with psychotic features 4. Schizoaffective disorder

Mood disorder with psychotic features, Schizoaffective Disorder & Scz are all part of schizophrenia spectrum Q’s you need to be asking are: – How independent are mood & psychotic symptoms?

– Does each type of symptom appear independently of the other? – If psychotic sxs

only arise

 in context of mood episode Mood disorder with psychotic features – nihilistic & hypochondrial delusions arise in context of depression – grandiose delusions arise in context of manic episode – If both types of symptoms prominent &

occur independently

of each other  Schizoaffective Disorder

But these can be difficult judgments

– Ask about 1 st episode: were mood symptoms prominent then?

– Be cautious: secondary depression is common in Scz

Comorbidity

Approx 50% PwScz, at least one comorbid psychiatric or medical condition (Green, Canuso, Brenner & Wojcik, 2003) • Depression, most common psychiatric comorbidity – associated with suicide • earlier studies estimated lifetime suicide rate 0f 10% • Palmer, Pankratz & Bostwick (2005) meta-analysis of studies observing PwScz for at least 2 yrs • Recent focus on  4.9% suicide rate (usually near illness onset) • Anxiety disorders (eg OCD) also present & complicate treatment

cannabis abuse

– prevalence studies (e.g. Ferdinand et al., 2005) • psychotic sxs present  OR 1.7 cannabis use present • cannabis use present  OR 2.8 psychosis present – longitudinal studies (e.g. Arseneault et al., 2002) • cannabis use by 15 yrs age  3.5 risk of developing psychosis – interaction with specific genotype (Caspi et al., 2005)

Cannabis

?

Genetic liability Scz

• Comorbid medical conditions also important (e.g.

diabetes

)

Brief note on medication side effects

• Neuroleptic Malignant Syndrome (rare toxic reaction to antipsychotics) rigid muscles, fever, confusion or coma, sweating, increased heart rate • Tardive Dyskinesia involuntary movements of tongue, mouth, jaw (sucking, chewing) & extremities, can be jerky, purposeless or rhythmic movements of arms & legs • Akathisia subjective experience of restlessness with fidgeting, pacing, rocking • Other motor disturbances stiffness & reduced spontaneity of movement, slurring, abnormal posturing & grimacing • • Clozapine (used when patient drug-resistant) can cause: Agranulocytosis (lack of white blood cells) fluid retention • Other problems dry mouth, constipation, blurred vision, decreased sex drive, drowsiness, weight gain

Further evidence of heterogeneity: Onset & prognosis

Onset can be acute (1 week) or insidious (> 6 months) Current focus on early psychosis intervention: • Important to identify prodrome – Phases: Prodrome, Acute & Residual – 3 types high-risk (prodrome) individuals (Yung, McGorry & colleagues) 1. brief time-limited frank psychotic symptoms 2. attenuated sxs (e.g. suspiciousness, confused thought & speech) 3. genetic high-risk (look at family history) & drop in function Course of illness variable: • Torrey (1988) – 25%

recovered (?)

, 25% independent, 40% community support, 10% suicide • Robinson et al. (2004) focused on sxs & socio-occupational functioning – delusions once a week – meet criteria for 2 yrs • 47.2% achieved symptom remission • 25.5% adequate social functioning •

only 13.7%

met full recovery criteria

Epidemiology

• • Refer http://www.qscr.uq.edu.au

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

Lifetime prevalence approx. 1% (

“roughly similar”

world)

higher incidence rates in migrants, developed countries, urban communities

across

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

Onset is variable

typical onset late adolescence to mid 20’s (median 19 years: Rey, 1992)

120 100 80 60 40 20 0 16-25 26-35 36-45 46-55 56-65 66-75 75+ MALES FEMALES

Epidemiology

• • • • • • Sex differences traditional wisdom: prevalence is

“roughly equally”

in men & women – QCSR study: median ratio of males to females is 1.4

childhood onset Scz more common in males amongst 17-18 yr olds, 4 males to 1 female later age of onset in females (3-5 yrs older on average) symptoms & prognosis generally worse for males – less responsive to antipsychotics, higher relapse, poorer long-term adjustment (social life, marriage, work, functioning, suicide) women show menstrual fluctuations in symptom severity • • Possible implications of sex differences different hormonal activity at puberty?

estrogen protection hypothesis?

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

Evidence for biological contribution

Genetic vulnerability

MZ TWIN

CHILD - 2 PARENTS

DZ TWIN

CHILD - 1 PARENT FULL SIB PARENT HALF SIB GRANDCHILD NEPHEW UNCLE/AUNT COUSIN POPULATION

0 10 20 30 40 50

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

Environmental risk factors

• Pregnancy complications (Jones & Cannon, 1998) Preeclampsia Perinatal brain damage 1 st trimester under-nutrition 2 nd trimester maternal flu

Relative risk 9 7 2 2

• Viral hypothesis – PwScz more likely to be born in winter – incidence of Scz higher in generations born during flu epidemics • Paternal age (Zammit et al., 2003) – risk of Scz increases in “dose-dependent” way with increasing – 1.3 OR increase for each 10-yr increase in father’s age • Urban risk – role of pollution or maternal stress • Incidence higher in migrants (Sharpley et al., 2001) paternal age

General conception

Genetic Liability Environmental factors

viral & pregnancy complications urban risk

Neurodevelopmental changes (early & late)

synaptic pruning abnormal D activity

Brain dysfunction

Brain dysfunction: structural changes

Postmortem evidence • brains of PwScz 6% lighter • enlarged ventricles • smaller temporolimbic regions (hippocampus & amygdala) with abnormal neuronal structure • frontal & temporal (rather than general) atrophy – prominent sulci (Gyrification Index) In vivo structural imaging (MRI) • enlarged ventricles • decreased cortical volume – frontal lobes & temporolimbic regions (hippocampus, amygdala, basal ganglia, thalamus – more specific details: Pantelis et al. (2003) Functional imaging (fMRI) findings similar Structural changes (frontal) generally associated with –ve sxs, less consistent associations with +ve sxs

Brain dysfunction: neurochemical abnormalities

Dopamine (D)

hyper

activity hypothesis • D agonists (amphetamines) induce psychotic sxs (paranoia) • antipsychotics block D receptors or D release • postmortem studies report increased D receptors in limbic regions – may explain age of onset (increased D activity in late adolescence) & role of stress in relapse (stress may induce D metabolism) But • D it’s not that straightforward • effects of antipsychotics not immediate

hyper

activity in subcortical regions, but D

hypo

activity in prefrontal cortex • different models: – different symptoms reflect different pathological processes (Crow) – interaction of different D systems (disruption of regulatory feedback loops: Weinberger) – other neurotransmitters may be more critical (glutamate & NMDA) • PCP (angel dust) induces loss of boundary experiences • PCP blocks glutamate receptors

Neuropsychological impairments

Neuropsychological profile generally consistent with neuroanatomical findings (i.e. temporolimbic & frontal deficits) • Memory – verbal: learning over trials – nonverbal: more variability • Executive function – set-shifting (WCST) – planning (Tower of London) – inhibitory control (Stroop, Hayling Sentence Completion) • Sustained Attention – CPT • Social cognition – emotion recognition (amygdala) • may be specific to processing of threat signals – theory of mind (mPFC)

Neuropsychological impairments

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

Neuropsychological impairments

2 1.8

1.6

1.4

1.2

1 0.8

0.6

0.4

0.2

0 Mental Non-mental EP Pats Conts

Neuropsychological impairments Don’t assume too much of clients • poor sustained attention • distractible • memory problems

– may not follow complex arguments

• miss social cues • fail to appreciate other people’s perspectives • misinterpret abstract or indirect comments (e.g. jokes, sarcasm) • lack of insight is common

Clinical heterogeneity

Patients are individuals Neuroanatomical & neurospychological findings based on

mean

differences • group differences

quantitative

rather than

qualitative

• lots of overlap & considerable individual variability How do we conceptualise clinical heterogeneity of Scz?

• • different subtypes of Scz patients – paranoid vs. disorganized vs. catatonic vs. undifferentiated – deficit vs. non-deficit Scz – core vs. non-core Scz

But

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

Clinical heterogeneity

Syndrome approach • • don’t subtype patients, subtype clinical sxs 1.

different clinical syndromes occur independently Crow’s dichotomy – Type I syndrome : positive sxs, responsive to neuroleptic medication, caused by neurotransmitter deregulation – Type II syndrome : negative sxs, associated with general cognitive deficits, caused by structural brain abnormalities 2. empirical studies (PCA analysis)  at least 3 major (relatively independent) syndromes – – – Reality distortion Disorganization Negative symptoms

But empirical solutions only as good as measures used

Clinical heterogeneity

Cognitive neuropsychological approach • focus on specific sxs (e.g. delusions or hallucinations) 1. Delusions – Maher (1974, 1988): abnormal experiences explain abnormal beliefs – Langdon & Coltheart (2000) 2-factor framework • abnormal experience not sufficient • Factor 1 processes lead to abnormal experiences that explain specific

content

of delusion • Factor 2 processes explain – JTC bias – Externalising bias – Social cognition deficits

adoption/persistence

of delusion

Clinical heterogeneity Cognitive neuropsychological approach

2. Auditory verbal hallucinations • Frith & colleagues: impaired monitoring of inner speech • Nayani & David: involuntary auditory memories • Badcock, Walters & colleagues: source monitoring problem + inhibitory deficit 3. Thought disorder • Rossell: Semantic deficits • Langdon; Sarfati: Theory of mind problems