12. Schizophrenia

• schizophrenia is a severe psychiatric disorder causing distortion of thoughts and perception, and may cause cognitive impairment

  • onset in adolescence or early adulthood
  • can have repeated episodes or progressive decline
• positive symptoms type II - presence of abnormal thoughts and behaviours

  • delusions
  • hallucinations
  • disorganised speech
  • thought disorder
• negative symptoms type I - absence of normal responses/behaviours

  • reduced expression of emotion
  • social withdrawal
• there is a strong genetic component to schizophrenia, but not fully. possible environmental causes:

  • viral infection in mother
  • autoimmune
  • poor maternal nutrition
• dopamine hypothesis of schizophrenia states that dopaminergic hyperactivity underlies schizophrenia

  • amphetamine abuse causes type I symptoms in a non-schizophrenic, and exacerbates type I symptoms in a schizophrenic
  • dopamine receptor agonists or L-DOPA also causes type I symptoms
• chlorpromazine was the first anti-schizophrenic treatment - decreases positive symptoms with low levels of sedation

  • typical/first generation neuroleptic
• typical neuroleptics bind to a variety of receptor sites, called dirty drugs

  • block dopamine receptors which is what treats schizophrenia
• atypical/second generation neuroleptics are more selective to dopamine receptors

  • more effective against negative symptoms
  • more effective against treatment resistant schizophrenia
  • fewer motor side effects
• clozapine is an atypical neuroleptic which has the best treatment against negative symptoms, however it as dangerous side effects
• dopamine pathways and schizophrenia

  • mesocortical pathway has hypofunction of dopamine - causes negative symptoms
  • mesolimbic pathway has hyperfunction of dopamine - causes positive symptoms

  this is why positive symptoms respond best to neuroleptics
• neuroleptic drugs work as an anti-emetic due to dopamine receptor block in the chemoreceptor trigger zone
• prolactin release from the pituitary is normally inhibited by dopamine - neuroleptics block this inhibition causing increased prolactin
• neuroleptic drugs block the dopamine receptor in the striatum causing motor effects

  • dystonias - involuntary movements like in parkinsons, reversible
  • tardive dyskinesia - involuntary movements that are slow developing, generally irreversible as a plastic change in the brain
• neuroleptic drugs also have non-dopaminergic side effects:

  • anti-muscarinic - dry mouth, constipation
  • postural hypotension
  • sedation due to histamine receptor block
• atypical neuroleptics more effectively block serotonin receptors, which is more effective for treating negative symptoms
• the dopamine hypothesis of schizophrenia may not be true as:

  • neuroleptics take weeks to work
  • dysfunction of dopaminergic pathways may not be primary cause of schizophrenia