L19 - Schizophrenia 2 Flashcards

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1
Q

How do genes operate across diagnostic categories?

A
  • Common alleles (polygenes)
  • Rare alleles: CNVs
  • Increased evidence for familial overlap inc. impairment of cognition and socially, developmental delay, perinatal risk factors
  • Significant co-morbidity
  • Genes are not for specific conditions, instead are for phentoypes that share characteristics inc. mental retardation, autism, ADHD, schiz, bipolar disorder
  • More CNVs = more likely to have disorder
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2
Q

What do specific, recurrent CNVs confer?

A
  • High risk of Schiz
  • CNVs are addition/deletion of DNA
  • 2.5% of schiz cases carries one prevalent CNV
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3
Q

What evidence is presented to support the polygenic model?

A
  • Purcell et al (2014) - 2,563 schiz cases vs 2543 controls –find a polygenic burden primarily arising from rare mutations distributed across many genes (cluster on synaptic
    plasticity/transmission).
  • Fromer et al (2014) - found that in schiz new (‘de novo’) mutations - these mutations are over-represented among glutamatergic post synaptic proteins (e.g. NMDA receptor complexes). Overlaps with autism and intellectual disability.
  • Convergence onto synaptic networks - glutamate hypothesis
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4
Q

Relationship between neuroleptic drugs and Schiz?

A
  • Neuroleptic drugs introduced in the 1950s
  • Correlates to the number of patients in mental hospitals
  • Important to remember that other things also supported this correlation: societial outlook
  • Can have positive/negative side effects
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5
Q

What was the role of anti-psychotic drugs?

A
  • Not targeted to specific brain regions but act generally
  • Affect dopaminergic and glutamate systems
  • Most people improve with the drug
  • But a lot of people also improve with a placebo
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6
Q

What is the Dopamine Hypothesis?

A

Based on 3 primary observations:
- Pharmacology: chlorpromazine helpful for schiz = blocks dopamine receptors
- Amphetamines: linked to excess dopamine = abuse of amphetamine are more likely to experience paranoia and psychosis
- Parkinsons: low dopamine in basal ganglia = L-Dopa increases dopamine but side effect is psychotic episodes
- Post-mortem: Schiz patients have increased D2 receptors = but they have taken drugs to alter their brain
- Velocardiofacial syndrome: reduced IQ = deletion of genetic material on chromosome 22 = high risk of psychotic episodes
- COMT is candidate gene = involved in metabolism for dopamine

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7
Q

What studies show support for the dopamine hypothesis?

A
  • Early studies = 2x increase in DA receptors – but many confounds, can’t rule out effect of medications.
  • Twin studies = Increased D2 receptors in healthy co-twin of person with Dx of schiz
  • First episode psychosis (drug free) - found higher levels of presynaptic DA in
    striatum
  • Also, higher striatal
    Dopamine in prodromal phase of schizophrenia (Howes et al 2009)
  • Image evidence of raised DA levels in striatum of 24
    prodromal cases showing. Image indicates the synthesis and accumulation of dopamine in the striatum during
    PET
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8
Q

What is the Glutamate hypothesis?

A
  • PCP, ketamine (glutamate antagonist) induces hallucinations and cognitive changes consistent with schiz
  • DA receptors inhibit release of glutamate leading to underactivity of glutamate receptors
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9
Q

Is schiz related to brain disease?

A
  • Enlarged ventricles: reduction in tissue volume, and brain areas bordering ventricles have shrunk
  • MRI studies of people with schiz show 3% reduction in whole brain volume
  • Enlarged ventricles not found in all schiz patients
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10
Q

What are neuropsychological tests for schiz indicating brain disease?

A
  • Poor performance on a range of neuropsych tests
  • Attention problems on continous performance test (CPT) & eye tracking dysfunction
  • Similar deficits observed in 1st degree relatives
  • Deficits seen in P’s during 1st episode (rules out effect of medication & hospitalisation
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11
Q

What was a study looking at neuropsychological deficits?

A
  • First episode schiz compared to IQ matched controls – multiple deficits in executive function, processing speed and verbal memory
  • Increasing impetus to the idea that cognitive changes
    maybe integral to
    aetiology of schizophrenia
  • Brain damage in twins is different when one suffers from schiz
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12
Q

What was a study looking at ventricular volume by time in patients

A
  • 107 first episode schiz. 51 had repeat MRIs at least 12 months later
  • T1 and T2 ‘Schiz’ group had greater ventricular volum
  • For those whose schiz symptoms did not improve, ventricular volume increased between T1 and T2
  • Schiz has a reduction in white matter volume found in first episode
  • White matter changes in temporal area predict later social functioning
  • Reduction in corpus callosum in the children of people with schiz
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13
Q

What is the structural damage beyond the ventricles?

A
  • Amygdala, hippocampus, thalamus and frontal lobes
  • Alterations in brain regions for schiz are also implicated in other dopamine disorders
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14
Q

What are wide spread brain abnormalities (evidence)

A
  • Pet scans show hypoactivity in brain of person with schiz
  • Reduced blood in frontal cortex during WISC
  • Impaired functioning of frontal lobes during cognitive tasks in early stages at high risk of schiz
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15
Q

What are the critiques of the brain abnormalities theory?

A
  • Time lag in actions of drugs: blockage of dopamine happens in hours but benefit takes weeks
  • 1/3 of patients do not respond to treatment
  • Pharmacology more effective for positive than neg symptoms
  • Not all studies find differences in DA receptors /alterations in brain functioning
  • Well-matched stuides show modest differences in ventricular volume which is affected by sex/age/head size/ethnicity/class = ventricular size can change over time
  • Dopamine abnormalities could be due to trauma
  • Bi-directional influence between brain/chemicals/env
  • Twin studies: could MZ rates be overestimated because they share env. MZ who share placenta have 60% concordance, but MZ who do not have 11% concordance
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16
Q

What is the gene x environment interaction?

A
  • Followed up adoptive children of women hospitalised for Schiz
    between 1960-79 vs. adoptive children without a Dx of Schiz. Studied degree of adversity in adoptive family environment. Only adoptive children who were raised in dysfunctional families AND had high risk of Schiz went on to develop Schizo
  • Concordance in MZ twins limited to 50% therefore also role of environment
  • Epigenetics – MZ twins who are discordant for Schiz show differences in gene expression
  • Could environmental insults turn on genes for Schiz in one twin and the other?
  • Only people had a parent with ‘schiz’ AND had birth complications showed brain abnormalities
    (enlarged ventricles)—deficits worse if both parents had ‘schiz’
  • Does genetic susceptibility predispose people to suffer MORE damage from environmental insults
  • Twin studies – MRI study of MZ and DZ twins discordant for ‘Schiz’ vs. healthy twins. Twin with ‘Schiz’ had smaller
    brain volume than well twin. Well P whose co-twin had ‘schiz’ had smaller brain volume than healthy control twins
  • Genetic risk for ‘Schiz’ associated with smaller brain volume—those who develop ‘Schiz’ suffer additional brain
    abnormalities that aren’t genetic
  • Those at genetic risk of ‘schiz’ fetal oxygen deprivation associated with brain abnormalities in later life
17
Q

What is the diathesis stress model of schiz?

A
  • Diathesis: genetic vulnerability = leading to brain abnormalities/disturbed neurotransmitter functioning
  • Potential stress factors: Prenatal trauma, birth complications, harsh critical family env/stressful life situation
  • Potential protective factors: communication style with fam and nurturing fam env/low stress in life
18
Q

What are the outcomes?

A
  • Up to 1/3 completely recover, and <1/4 remain permanently affected
  • “Social recovery” occurs in 40-45% of cases
  • Outcome generally better in developing countries than in the west due to greater social inclusion, quicker return to valued roles, less stigmatisation, increased optimism,
    community involvement
19
Q

What were cognitive factors in cognitive factors?

A
  • Negative symptoms of schizophrenia associated with lower self-esteem and negative self-concept about interpersonal abilities
  • Psychotic disorders appear to reflect low self-
    esteem and that this might make people feel they ‘deserve’ to be persecuted
  • Study showing people with diagnosis of
    schizophrenia appear to have a bias against disconfirmatory evidence
  • Meta-analysis showing people with psychosis require
    less information to make decisions
20
Q

What is the aim of the cognitive model?

A
  • Lead to positive symptoms and to integrate with social factors
  • Supported by empirical evidence
  • Incorporates disruption by automatic cognitive processes and maladpative conscious appraisals
  • Covers delusions and hallucinations and posits a central role for emotion
21
Q

What is the background of the cognitive model of psychosis?

A
  • Occurs in people of vulnerable disposition & typically follows adverse event/illicit drugs/isolation
  • Social isolation contributes to psychotic appraisal
  • Disruptions in attention, perception, judgement
  • At onset most prominent symptoms = delusional beliefs and hallucinations
  • Trigger→disruption cognitive processes→emotional changes→search for explanation of cause
  • Trigger→disturbed affect→activates biased appraisal processes and maladaptive schema
  • CBT depends on an effective therapeutic alliance between clinician and client
  • Several research studies have now investigated the efficacy of these approaches
22
Q

What is the cognitive model of psychosis?

A
  • Biopsycho-social vulnerability = stressful events = emotional changes = cog dys and anomalous exp = appraisal of exp = pos symptoms = maintaining factors
  • Appraisal is influenced by: reasoning/attribution biases, dysfunctional schemas of world, isolation and adverse env
  • Maintaining factors: reasoning, emotional processes, appraisal of psychosis
23
Q

How can CBT be useful?

A
  • Encourages people to
    make links between thoughts, feelings and behaviours and helps to re-evaluate perceptions, beliefs and reasoning about targeted symptoms
  • Gathering data to understand more about someone’s experiences
  • Helping to explore the origins of one’s worldview
  • Testing out delusions with behavioural experiments
  • Addressing comorbid features such as anxiety and depression
  • Helping access social support
  • Learning to dialogue with one’s voices / stand up to them
  • Learning meta-cognitive strategies such as mindfulness
  • Learning tools for reducing the impact of voices
24
Q

What are the three cognitive models of psychotic experiences?

A
  • Garety: model explaining development and maintenance of pos symptoms
  • Morrison: model explaining how people interpret anomalous experiences and how this maintains experiences
  • Freeman: model explaining persecutory delusions
25
Q

What is family intervention for psychosis?

A
  • FI should be available to families who are living with someone with psychosis or who are in close contact
    with them
  • High levels of ‘expressed emotion’ (EE) within a family has been shown to be an effective predictor of
    relapse in schizophrenia.
  • High EE is harmful when it is associated with critical and hostile comments and emotional over-involvement towards the person with psychosis
  • Aim to change communication between the person with ‘schizophrenia’ and their close relatives
  • Often includes CBT techniques.
  • Most of the current evidence base is for cognitive-behavioural interventions and family interventions
26
Q

How to combat hearing voices?

A
  • Voice identity
  • Voice characteristics
  • Triggers for the voices
  • History of the voices
  • Person’s life history
  • Voices might represent someone/something and might represent problems