1 / 40

Schizophrenia: Overview

Schizophrenia: Overview. Background Schizophrenia symptoms/syndromes Schizotypal personality Dopamine hypotheses Genetic effects on prefrontal functioning in SZ Neurodevelopmental hypothesis Neuropsychological accounts. Psychosis vs. Schizophrenia.

elvin
Download Presentation

Schizophrenia: Overview

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Schizophrenia: Overview • Background • Schizophrenia symptoms/syndromes • Schizotypal personality • Dopamine hypotheses • Genetic effects on prefrontal functioning in SZ • Neurodevelopmental hypothesis • Neuropsychological accounts

  2. Psychosis vs. Schizophrenia • Psychosis is a syndrome (mixture of symptoms) – delusions and hallucinations • Psychotic disorders schizophrenia schizoaffective disorder schizophreniform disorder drug-induced psychoses • Other disorders have psychosis as an associated feature

  3. Schizophrenia Basics • Most common psychotic illness • Affects 1% of population • costs billions $$$ p.a. • Definition • Must last >6 months • incl. At least one month of halluc., delusions, grossly disorganised speech/behaviour • Can be very severe • 25-50% of patients attempt suicide

  4. Delusions • Misrepresentations of perceptions or experience • Most common are persecutory • Others referential; somatic; religious; grandiose

  5. Hallucinations • Disordered perception perceptions without corresponding physical stimuli • Most commonly auditory but can occur in any sensory modality

  6. 5 Symptom Dimensions in Schizophrenia • Positive symptoms • Negative Symptoms • Cognitive Symptoms • Anxiety and Depressive Symptoms • Aggressive Symptoms

  7. Positive Symptoms • Additions to normal function • Delusions • Hallucinations • Distorted language/communication • Disorganised speech / behaviour • Catatonic behaviour • Agitation

  8. Negative Symptoms • Losses of normal function Affective flattening Alogia Avolition Anhedonia Attentional impairment Blunted affect, emotional withdrawal, poor rapport, passivity, apathetic social withdrawal

  9. Negative Symptoms • Different aetiologies primary (a core feature) secondary to:- +ve symptoms depression extrapyramidal symptoms environmental depreivation

  10. Cognitive Symptoms • Thought disorder • Odd use of language incoherence, loose associations, neologisms • Impaired attention / cognition reduced verbal fluency learning/memory executive functions

  11. Syndromes in Schizophrenia • Type 1 vs Type 2 (Crowe) • Liddle’s 3-syndromes scheme reality distortion(positive) psychomotor poverty (negative) disorganisation

  12. What Are Schizotypal Personality Traits? • Stable traits in healthy individuals • Tendencies to show features of behaviour/cognition that are qualitatively similar to those of schizophrenic patients • Underlying continuum model

  13. Schizotypal Personality: Multidimensionality Schizotypal personality has 3 or 4 correlated factors … Positive schizotypy Disorganised schizotypy Negative schizotypy 4th factor = Impulsive nonconformity: Is this really schizotypal personality?

  14. Schizotypal Personality Measures • Positive Schizotypy • OLIFE: Unusual experiences (UnEx); • SPQ: Cognitive-perceptual factor • Negative Schizotypy • OLIFE: Introvertive anhedonia (IntAnh); SPQ negative factor • Disorganised Schizotypy • OLIFE: Cognitive Disorganisation (CogDis); SPQ Disorganisation

  15. Example OLIFE Items • Positive Schizotypy: Measure = Unusual Experiences (30 items) -I have felt that I have special, almost magical powers -Do you ever feel that your thoughts don’t belong to you? -Sometimes my thoughts are as real as actual events in my life

  16. SPQ Subscales • Positive (Cog-Perceptual) • Unusual perceptions; odd beliefs; • ideas of reference; suspiciousness • Negative (Interpersonal) • No close friends; excessive social anxiety; constricted affect; susp • Disorganised Schizotypy • Odd behaviour; Odd Speech

  17. Why Study Schizotypal Personality Traits? • Testbed for schizophrenia in readily-available, healthy individuals • Performance of high scorers should be similar to schizophrenics • Behaviour not contaminated by medication, illness, hospitalisation etc

  18. More Reasons to Study Schizotypal Personality Traits • May find specific associations with one schizotypal factor • Generates predictions for associations with specific SZ symptoms

  19. Schizotypal Personality Traitsand Psychosis Proneness • Alternative definitions of schizotypy -a prodrome for schizophrenia -schizotypal personality disorder -psychosis proneness • Follow-up studies of high-scoring subjects on schizotypal personlity traits

  20. Schizotypal Personality Follow Up Studies • Kwapil, Chapman and Chapman -10 year follow-ups -small increase in Sz for positive schizotypy measures -Follow-ups of high scorers on the ImpNon dimension did not show inc. Sz but small increases in other psychopathologies

  21. Neuroscience of Schizophrenia • Dopamine and schizophrenia • Recent genetics advances • Neurodevelopmental hypothesis

  22. Brain Dopamine Pathways • Nigrostriatal degenerates in Parkinson’s disease • Mesolimbic positive symptoms of schizophrenia • Mesocortical neg symptoms of schizophrenia • Tuberoinfundibular

  23. Signals of reward availability Addictive drugs: opiates, cocaine, cannabis, nicotine Food/drink EBS Sex Effective goal-directed behaviour

  24. Evidence for DA Hypothesis • Stimulant drugs -release DA -amphet/cocaine abuse -> paranoid psychosis • Antipsychotic drugs • which are effective at treating positive symptoms are DA receptor (DR) blockers esp. D2 DR

  25. Mesolimbic DA Hypothesis • Hyperactivity of mesolimbic DA mediates positive symptoms of psychosis • Accounts for these psychotic symptoms whether in SZ or other disorders

  26. Mesocortical DA Hypothesis • Deficit of mesocortical DA mediates negative and cognitive symptoms of psychosis - more controversial - affects areas such as DLPFC - degenerative in some SZ patients - may be primary deficit - may be secondary drug effect

  27. New Developments in DA Hypotheses of SZ: 1 Good recent review at:- http://www.acnp.org/g4/GN401000115/Default.htm

  28. New Developments in DA Hypotheses of SZ: 2 Recent advances in molecular genetics make it possibly to explore the effects of … specific genetic polymorphisms relevant to the DA hypothesis

  29. Studies of the COMT gene see Egan et al (2001). Proceedings of the National Academy of Sciences (PNAS) 98, 6917-6922

  30. The COMT gene and SZ • Catechol-o-methyl transferase is a catabolic enzyme that degrades DA • The COMT gene has two variants which affect the functioning of the gene (val and met alleles) • The gene is on chromosome 22 close to regions which have been implicated in linkage studies with SZ • Family and association studies have implicated the COMT gene in SZ

  31. Egan et al 2001: 1 • Argued that “abnormal PFC function” is a useful intermediate phenotype for SZ • Intermediate phenotypes are more likely to be related to gene function than the clinical diagnosis • SZ show reliable PFC disturbances on cognitive tests • So do healthy sibs inc. MZ co-twins

  32. Egan et al 2001: 2 • DA plays role in modulating PFC during working memory (WM) tasks • As COMT gene affects prefrontal dopamine levels then may affaect WM • COMT knockout mice have increased DA in PFC and enhanced memory performance

  33. Egan et al 2001: 3 • Measured WM and exec function using Wisconsin Card Sorting Test (WCST) -WCST activates PFC -DA-mimetic drugs improve WCST performance in SZ • Measured prefrontal neurophysiology using fMRI and the n-back WM task -task activates DLPFC -in SZ, and unaffected sibs, DLPFC activation is inefficient

  34. Egan et al 2001: Results Controls Sibs patients

  35. Egan et al 2001: Results • fMRI during the n-back task showed, for patients and sibs, that DLPFC and ACC activation efficiency was affected by genotype:- val/val < val/met < met/met

  36. Egan et al 2001: Results • Analysed 104 family trios (2 parents plus case) • In 126 gene transmissions from heterozygous parents to probands the val allele was transmitted 75 times (p=0.03) • In unaffected sublings 77 val vs 87 met transmissions

  37. The COMT gene and schizotypy Various studies have shown that the COMT gene may be linked to schizotypal personality (Stefanis et al, 2002, 2004), although what aspects are not clear, with high schizotypy associated with presence of val allele

  38. Neurodevelopmental Hypothesis of Schizophrenia • Proposes that Sz arises from ?genetic? abnormalities in fetal brain development (evidence?) • Why should such this give rise to peak incidence of Sz in teens and early 20s? • Ans: Adolescent neural restructuring reveals earlier deficit (evidence?) • Maybe additional neurodegeneration during symptomatic phase of disease

  39. Neuropsychological accounts of SZ • Usually propose a deficit in a specific cognitive process as responsible for a specific subset of SZ symptoms • Thus SZ perform worse/differently from controls on a cognitive task designed to measure the specific process

  40. Neuropsychological accounts of SZ: Examples • Latent Inhibition (Gray) • Negative Priming (various) • Contextual processing (various)

More Related