psychopathology

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psychopathology

• Schizophrenia

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Schizophrenia Diagnosis

• Symptoms
• 2 or more, present for a significant portion of
  time, for a month unless treated
• Delusions paranoid most of the time
• Hallucinations auditory, visual, somatic, etc
• Disorganized speech (derailment or incoherence)
• Grossly disorganized or catatonic behaviour
• Negative symptoms affective flattening, alogia,
  avolition, anhedonia, attention (lack of)
• If delusions are bizarre or hallucinations are
  consistent on one voice making comments about the
  persons activities and having conversations,
  only one symptom is necessary

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Schizophrenia Diagnosis

• Social / occupational dysfunction
• Persists for at least six months Includes a
  month of active symptoms and prodromal or
  negative symptoms
• Schizoaffective and mood disorder exclusion no
  mood disorder, or a very brief one has occurred
  during the active phase
• Substance abuse/general medical condition
  exclusion
• Relation to a pervasive developmental disorder
• Course
• Episodic with interepisodic residual symptoms
• Episodic with no interepisodic residual symptoms
• Continuous
• Single episode in partial remission
• Single episode in full remission
• Other unespecified pattern

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Schizophrenia Diagnosis

• Types
• Paranoid
• Prominent delusions and hallucinations
• Non prominence of disorganized speech,
  disorganized or catatonic behaviour, flat or
  inappropriate affect
• Disorganized
• Prominent disorganized speech, disorganized
  behaviour, flat or inappropriate affect
• Not catatonic in nature
• Catatonic
• Catalepsy or stupor
• Excessive motor activity
• Extreme negativism or mutism
• Posturing, stereotyped movements, mannerisms,
  grimacing
• Echolalia and echopraxia
• Undifferentiated
• Residual

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Schizophrenia Facts

• 1 of the general population affected
• 2-3 have schizotypal personality disorder
• 33 billion dollars in annual costs to the US
• 30 of the homeless are schizophrenic

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Schizophrenia Anatomopathology

• Early in the disease there is a reduction to the
  left globus pallidus no connection between
  frontal lobes and basal ganglia
• Frontal lobes do not respond to stimulation with
  increased blood flow
• Cortex in medial temporal lobe is thinner, left
  anterior hippocampus is smaller
• Lateral and third ventricles enlarged with
  widening of sulci in temporal and frontal lobes
• Changes seen in prominent negative symptoms

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Schizophrenia Causes

• Genetic predisposition
• Developmental injury of neurons in white matter
  under layer VI or cortical subplate.
  Significantly reduced in frontal and temporal
  cortex but increased 3 mm underneath (abnormal
  migration)
• Viral infections during pregnancy
• Premature switch off of genes encoding for
  migration?
• Excessive dopaminergic transmission in the
  mesolimbic system positive symptoms
• Decreased activity in the mesocortical
  connections of prefrontal cortex negative
  symptoms

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Schizophrenia causes

• D2, D3 and D4 blockade
• Increased sensitivity over time
• Increased dopaminergic activity
• Downregulation of 5HT2 receptors (stimulation is
  hallucinogen)
• PCP produces schizophrenia like symptoms
• PCP binds dopaminergic and NMDA glutamatergic
  receptors
• PCP enhances dopamine release in the mesolimbic
  pathway while it block dopamine release in the
  mesocortical system

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Schizophrenia Family studies

• Definitely familiar
• Risk for relatives 2nd degree 4 1st degree
  9 DZ 17 MZ 48
• Amongst 1st degree 6 parents, 9 siblings and
  13 offspring if one parent is affected but 46
  if both are affected
• Affected offspring have
• parents severely affected by the disease
• unstable families with more hospitalizations
• Perinatal complications
• Attention problems in childhood
• Personality disorders

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Schizophrenia Twin and adoption studies

• TWIN STUDIES
• Concordances for MZ between 41-65 and DZ 0-28
• Heritability is up to 80
• Discordance most probably environmental for MZ
• ADOPTION STUDIES
• Risk does not decreased if reared apart by
  non-affected parents
• Findings support genetic familial studies
• Shared or non shared environment seem to play no
  major role in the development of the disease.

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Schizophrenia one or several?

• Continuum vs.
• Discrete
• I mild, positive symptoms
• II severe, negative symptoms
• I more genetic or familial than II
• Solution will be molecular A set of genes for
  all or sets of genes for each type
• Endophenotypes

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Schizophrenia Looking for genes

• Association studies not conclusive yet even with
  candidate gene approach
• Linkage has failed to find anything
• Multiple genes with a small effect?
• Genes are neither necessary nor sufficient.