Dopamine hypothesis

• An excess of dopamine is associated with positive symptoms of schizophrenia due to high numbers of receptors receiving dopamine and causing the neurons to fire
• Amphetamine stimulates nerve cells containing dopamine, causing it to flood in the synapse increasing neural activity
• Chlorpromazine blocks dopamine activity in the brain by reducing activity in neural pathways, reducing positive symptoms
• Hyperdopaminergia- high levels of dopamine in the subcortex
• Hyperdopaminergia causes positive symptoms and hallucinations
• Hypodopaminergia- low levels of dopamine in the prefrontal cortex
• Hypodopaminergia causes negative symptoms
• Schizophrenia is likely due to both hyperdopaminergia and hypodopaminergia
• Dopamine pathways relevant to schizophrenia symptoms

  • Overactive mesolimbic pathway- positive symptoms
  • Dysfunctional mesocortical pathway- negative symptoms
• Treatments- strengths

  • Chlorpromazine artificially lowers dopamine levels which reduces positive symptoms
• Holistic explanations- weakness

  • Hyperdopaminergia is caused by a mutation in the DISC1 gene, meaning dopamine is not regulated or controlled in the brain due to a genetic mutation
• Dahoun et al (2017)

  • an abnormal DISC1 gene is associated with presynaptic dopamine dysregulation
• Schizophrenics often have an abnormally high number of D2 receptors on the receiving neurons, causing more dopamine binding and more neurons firing
• Beta hydroxylase is an enzyme that breaks down dopamine. If its own levels are insufficient, then there is an excess of dopamine causing hyperdopaminergia
• Dopamine dysregulation was proposed by Howes and Kapur (2009), they hypothesise that dopamine dysregulation in the striatum is what causes the onset of schizophrenia
• Drug research- strength

  • Amphetamine drugs are dopamine agonists, meaning they stimulate the neuron that produces dopamine, causing it to flood the synapse
  • Amphetamines cause symptoms similar to positive symptoms of schizophrenia: hallucinations and delusions
  • Dopamine antagonists (drugs that block D1 receptors) reverse the effects successfully
• Contradicting research- weakness

  • Depatie and Lal (2001)
  • A dopamine agonist apomorphine stimulates D2 receptors
  • Does not cause psychotic symptoms in non-psychotic patients
  • Does not increase symptoms in psychotic patients
• Role of glutamate- weakness

  • PCP is a strong antagonist of glutamate receptors and blocks them
  • When blocked, the excitatory effect of glutamate is reduced
  • Results in negative symptoms of schizophrenia