1. Introduction to Schizophrenia

What is schizophrenia?

A psychiatric disorder in which previously normal cognitive abilities & behaviours become disturbed

What are the symptoms and common characteristics of schizophrenia?

• Manifested by:

  • Positive symptoms: delusions, hallucinations, unusual or disorganised behavior

  • Negative symptoms: lack of activity, loss of interest, unresponsiveness

• People with schizophrenia are rarely violent

• Suicide & self-harm are more common

What does 'schizophrenia' mean?

• First used by Eugen Bleuler in 1908 to describe a 'splitting of psychic functions'

• From Greek: 'split' (schizo) and 'mind' (phren)

• Refers to disconnection from reality - can’t tell whats real or not

What are the key dopamine pathways involved in schizophrenia & their functions?

• Mesocortical pathway → cognition & executive function

• Mesolimbic pathway → emotional behaviour

• Nigrostriatal pathway → motor control

• Tuberoinfundibular pathway → prolactin regulation

How do dopamine imbalances in brain pathways relate to schizophrenia symptoms?

• Mesocortical (↓ dopamine) → negative symptoms:

  • Alogia (↓ speech)

  • Affective flattening

  • Avolition (↓ activity)

• Mesolimbic (↑ dopamine) → positive symptoms:

  • Delusions

  • Hallucinations

  • Disorganised thought, speech & behaviour

• Nigrostriatal (↓ dopamine from treatment) → motor side effects

• Antipsychotics ↓ dopamine → help positive symptoms but may worsen negative & cause motor side effects

Is schizophrenia caused by neuronal death?

• Possibly linked to neuronal loss, though not proven for all cases

• Common finding: larger lateral ventricles in affected individuals → suggests cortical tissue loss

• MRI scans show:

  • Loss of grey matter in parietal cortices in teens with schizophrenia

  • Spread of tissue loss into sensory & motor regions over time

• More pronounced in males than females

What is the dopamine hypothesis of schizophrenia?

• Based on D₂/D₄ antagonists improving symptoms

• Amphetamine abuse (↑ dopamine, 5HT, noradrenaline) = more in synaptic cleft = schizophrenia-like psychosis

• Linked to abnormalities in mesolimbic & mesocortical pathways

• Pathways start in ventral tegmental area & project to amygdala, nucleus accumbens & cortex

What are the biochemical theories of schizophrenia?

• NMDA Hypothesis: NMDA blockers (e.g. ketamine) → schizophrenia-like symptoms; NMDA enhancers (e.g. glycine) show benefit

• Single-Carbon Hypothesis: Folate pathway disruption affects brain metabolism

• Membrane Hypothesis: ↓ fatty acids & ↑ phospholipase A₂ → impaired cell signalling across cell membranes

What neurotransmitters are involved in schizophrenia?

• Dopamine: D₂ blockers ↓ positive symptoms; amphetamines ↑ psychosis

• Glutamate: NMDA antagonists (e.g. ketamine) → psychosis-like symptoms

• GABA: ↓ synthesis & reuptake in prefrontal cortex

• Acetylcholine: ↓ cholinergic receptors in hippocampus, thalamus & striatum

• Serotonin: 5-HT₂A activation linked to psychosis