biological basis of schizophrenia - AY

• positive symptoms of psychosis

  abnormal perceptions: hallucinations (mainly auditory, but can be other sensory modalities)

  abnormal ideas: delusions (persecution, grandiose, hypochondriacal)

  thought disorder: thought insertion of withdrawal, derailment, poverty of speech content
• symptoms of psychosis

  negative symptoms: - reduction of normal behaviour

  emotional disorders: emotional flattening, withdrawal

  motor and behavioural disorder: abnormal posture, catatonia
• symptoms of psychosis

  cognitive symptoms

  • abnormalities of attention, memory and executive cognitive function
• diagnosis of schizophrenia

  DSM + ICD

  at least one present most of the time for more than a month

  • thought insertion, withdrawal or broadcast
  • delusion of perception
  • delusion of control
  • hallucinatory voices
  • persistent bizarre delusions
• diagnosis of schiz

  at least 2 present most of time for more than a month

  • persistent daily hallucinations
  • incoherent speech
  • catatonic behaviour such as posturning
  • negative symptoms such as marked apathy, blunted

  exclusion criteria: mood disorder, drug taking, neurological conditions
• phenomenology of schizophrenia

  • symptomatology differers greatly between patients
  • symptomology in individual patients shows periodic fluctations
  • prevalence rate: 0.5%
  • peak onset (20 + 39)
• genetic influence

  • parents and siblings of sufferers 10 times more likely
  • children of sufferers 15 times more likely
• genetic influence:

  • concordance rate in identical twins: 40-60%
  • concordance rate in fraternal twins : 10 - 15%
  • if entirely genetic, concordance rates in twins would be: identical 100%, fraternal: 50%
  • strong genetic componement, not entirely genetically determined
• biological factors

  • prenatal exposure to viruses
  • high incidence in people born after major flu epidemics
  • high incidence in people born in the spring
  • pregnancy and delivery complications: high incidence in people who had forceps deliveries
• environmental factors affecting schizophrenia

  social factors

  • life experiences
  • family relationships; upbringing
• structural abnormalities in schizophrenia

  • structural abnormalities in the brain are common in schizophrenia: but no signature abnormality has been identified
  • reduced temporal lobe volume and enlarged ventricles
  • reduced metabolic activity in frontal cortex
• the dopamine theory

  amphetamine causes symptoms very similar to positive symptoms - does not cause negative symptoms

  dopamine antagonists provided the first pharmacological treatment for schizophrenia - do not treat negative symptoms
• dopamine theory

  some evidence of increased dopamine function in schizophrenia

  • changes in dopamine function may be a response to long term drug treatment

  therefore schizophrenia may be associated with increased dopamine function: however, the dopamine theory cannot account for full spectrum of the condition
• drug induced psychosis

  • LSD
  • 5HT receptor agonist
  • causes hallusionations

  increased 5HT function may be linked to schizophrenia- the serotonin theory
• drug induced psychosis

  • Phencyclidine
  • antagonist at glutamate receptors (similar effects with ketamine)
  • causes behavioural changes in normal people with receptors in normal people which resemble positive, negative and cognitive symptoms of schizophrenia
• are there changes in glutamate in schizophrenia

  • reduced levels of glutamate
  • increased cortical glutamate receptors
  • increase binding to glutamate receptors in cortex, basal ganglia and hippocampal formation
  • decreased glitamate uptake sites in cingulate cortex
• schizophrenia - a wholistic view

  • positive symptoms may be a result of impaired function in temporal lobes
  • people with temporal lobe damage show behaviours resembling positive symptoms
• negative symptoms may be a result of impaired function in prefrontal cortex

  • schizophrenics perform poorly on tasks requiring prefrontal cortex
  • people with frontal lobe damage show behaviours resembling negative symptoms
  • however these impairments alone are not sufficient to invoke schizophrenia
• unified theory of neurochemistry of schizophrenia

  • therapy targeted at glutamic systems is difficult
  • therapy with dopamine antagonists is ineffective or even detrimental
  • therapy with dopamine/serotonin antagonists treats both positive and negative symptoms
  • therapy with dopamine antagnoists is ineffective or even detrimental
• without pharmacological intervention

  • some improvements but never complete recovery
  • more rigorous studies suggest that around 20% of patients showed near full recovery
  • with pharma leads to 50%
• chlorpromazine

  • mid 1950s
  • drug used to treat surgical shock
  • patients reported a feeling of well-being
  • therefore tried on psychotic patients
  • found to reduce psychotic symptoms
  • mid 1960s
  • ascertained that chlorpromazine is an antagonist dopamine receptors
• typical antipsychotics

  • e.g. chlorpromazine, haloperidol
  • dopamine receptor antagonists
  • reasonably effective at treating positive symptoms
  • not good at negative or both
  • 40-50% of patients may not show improvements
  • severe motor side effects
  • similar to symptoms of parkinson's disease
  • due to decreasing dopamine function in the nigrostriatal pathway
• parkinson side effects

  • parkinson's disease caused by degeneration of the nigrostriatal pathway
  • causes dopamine deplection
  • treated with l-dopa
  • restores dopamine levels in striatum
  • also increases dopamine levels elsewhere in the brain
• clozapine - good antipsyhcotic potency, but minimal side effects

  reduces negative and cognitive symptoms

  effective in patients who are refractory to other antipsychotics

  but

  • causes leukopenia (reduced white blood cells)
  • blood cell count must be monitored weekly - adds substantially to patient inconvenience and to the cost

  causes excessive salivation

  used in patients who do not respond to other treatments
• atypical antipsychotics

  • antipsychotic but with reduced extrapyramidal side-effects
  • more effective against negative and cognitive symptoms
  • act on many different receptor types

  but:

  • still not effective in all patients
  • can be quite variable effects in different patients
  • have significant side effects, which may limit compliance
  • may not work as quickly as typical antipsychotics
• treatment

  • first line - use atypical antipsychotics
  • use of typical antipsychotics mainly restricted to acute patients where more rapid onset is required
  • typical antipsychotics also used for non-complisnt patients who require monthly injections
  • still a significant proportion of patients who do not respond well to treatment
  • cognitive and negative symptoms respond poorly to treatment
• alternatives to pharmacological therapy

  psychological therapy: cognitive behaviour therapy

  family therapy