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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): 1st 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): 1st-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 (2nd person) – conversing (3rd 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 1st 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 4.9% suicide rate (usually near illness onset) • Anxiety disorders (eg OCD) also present & complicate treatment • Recent focus on 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) ? Genetic liability Cannabis 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 </= 2 (SAPS) & negative sxs </= 3 (SANS) – living day-to-day without supervision & social interactions > 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” across world) • • higher incidence rates in migrants, developed countries, urban communities 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 MALES FEMALES 60 40 20 0 16-25 26-35 36-45 46-55 56-65 66-75 75+ 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) Relative risk Preeclampsia 9 Perinatal brain damage 7 1st trimester under-nutrition 2 2nd trimester maternal flu 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 paternal age – 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) 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) hyperactivity 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 it’s not that straightforward • effects of antipsychotics not immediate • D hyperactivity in subcortical regions, but D hypoactivity 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 EP Pats Conts Mental Non-mental 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 • different clinical syndromes occur independently 1. 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 adoption/persistence of delusion – JTC bias – Externalising bias – Social cognition deficits 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