AmphetamineInduced Psychosis

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Amphetamine-Induced Psychosis
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Amphetamine (AMPH)

• Artificial stimulant
• Related to dextroamphetamines and
  methamphetamines
• Increase breathing, heart rate, blood pressure
• Visual and auditory hallucinations, lack of
  organization, self-consciousness, erratic and
  compulsive behaviour
• May be medically prescribed for treatment of
  Parkinsons

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Amphetamine Action

• AMPH acts on the dopamine system
• Blocks DA reuptake
• Actively stimulates production of DA

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Animal Models

• Amphetamine has been used to create
  schizophrenic-like symptoms in animals to try to
  create an animal model of schizophrenia
• Rodents
• -studies have found that AMPH and PCP both
  induced behaviours related to the positive
  symptoms of schizophrenia
• -BUT only PCP was found to induce social
  withdrawl (a negative symptom)

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Animal Models

• Rhesus Monkeys
• -After 12 weeks of intermittent, escalating, low
  doses of AMPH, researchers did a post withdrawl
  AMPH challenge
• -After the challenge, monkeys displayed
  hallucinatory-like behaviours, static postures
  and persistent behavioural depression
• -AMPH induced both positive AND negative symptoms
  of schizophrenia in Rhesus monkeys

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Human Models

• Amphetamine-Induced Psychotic Disorder DSM-IV
  diagnosis
• -Prominent hallucinations or delusions
• -Developed during or within a month of substance
  intoxication or withdrawl
• -Disturbance is not better accounted for by
  non-substance induced psychotic disorder
• -Disturbance does not occur exclusively during
  course of a delerium

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Human Models

• Case studies have reported on instances of
  amphetamine users developing a schizophrenia-like
  syndrome even after they have stopped using the
  drug
• Typical case
• -psychotic symptoms develop 2 months after
  giving up amphetamines
• -no apparent diathesis for schizophrenia

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Human Models

• -rapid response to neuroleptics, re-emergence of
  positive symptoms in response to decrease in dose
• -negative symptoms occur between episodes of
  positive symptoms

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Problem of Correlation

• Does chronic amphetamine abuse cause a
  schizophrenic-like syndrome?
• OR.Does amphetamine abuse precipitate onset of
  schizophrenia?
• AMPH can induce schizophrenia-like syndrome
  during intoxication even in animals without a
  genetic predisposition

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Proposed Mechanism for Chronic Amphetamine-Induced
Psychosis

• AMPH use (by anyone) causes increased
  pre-synaptic DA activity which result in positive
  psychotic symptoms
• Chronic exposure will result in pre-synaptic
  neuron degeneration causing a relative state of
  DA deprivation, may result in negative symptoms
• Decrease in DA results in increased
  post-synaptic neuron sensitivity which will
  result in positive symptoms during times of
  transiently elevated DA

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Problems

• When does diagnosis leave the realm of
  Amphetamine-Induced Psychosis and become
  schizophrenia?
• Majority of amphetamine abusers dont develop a
  chronic schizophrenic-like syndrome

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Conclusions

• Amphetamines target the dopaminergic system and
  can cause a syndrome of the positive and negative
  symptoms of schizophrenia
• For this reason, amphetamines are currently being
  experimented with in animals in an effort to
  create a model of schizophrenia
• Research has shown that chronic use of
  amphetamines can also cause a chronic
  schizophrenia syndrome after withdrawl from the
  drug

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Conclusions

• The mechanism behind this chronic syndrome
  apparently involves the sensitization of
  post-synaptic DA receptors
• One problem with this hypothesis is that not all
  amphetamine users develop the chronic
  schizophrenic-like syndrome, thus implicating
  that there is also may be an underlying diathesis
  involved (which is not apparent)