LEC 13: Schizophrenia

What is Schizophrenia?

A psychotic disorder that affects how people think, feel and behave

Difference between positive, negative and cognitive symptoms of schizophrenia and examples

• Positive symptoms: symptoms that go beyond normally occurring experiences

  • hallucinations (auditory, visual)

  • delusions

• Negative symptoms: characterized by a deficit or absence in a normal behaviour

  • apathy

  • limited thought/speech

• Cognitive symptoms: characterized by erratic changes in speech, motor behaviour and emotions

  • disorganized speech

  • inappropriate emotional reactions

DSM-5 diagnostic criteria for schizophrenia

• must have at least one of:

  • delusions

  • hallucinations

  • disorganized speech

• diminished level of function

• long-lasting symptoms

• not due to drugs or other medical conditions

Development of schizophrenia

• usually diagnosed in late adolescence or early adulthood

• most people with schizophrenia have a prodromal stage which is a 1-2 year period where subdued symptoms begin to appear

Prognosis of schizophrenia

• the prognosis is poorer than for most other disorders, but recovery/remission is more likely given:

  • good social adjustment prior to onset

  • a low proportion of negative symptoms

  • a good social support system

Etiology of schizophrenia

Genetically:

• clear evidence for a genetic link

Perinatal factors:

• evidence that environmental stressors can unlock the predisposition for schizophrenia

• fetal exposure to viruses like influenza may subtly damage the fetal brain

• pregnancy and delivery complications

• prenatal nutrition/stress

Anatomical basis of schizophrenia

• enlarged lateral ventricles, suggests that nearby parts of the brain did not develop or have atrophied

• reduced dendritic spine density in the prefrontal cortex

• reductions in the size of the hippocampus, due to degradation and correlated with illness severity

• disorganized neurons in the hippocampus

Treatment for schizophrenia

• chlorpromazine (Thorazine) had amazing success when given to psychotic patients

• chlorpromazine and related drugs are called antipsychotics

Mechanism of action of the drugs used to treat schizophrenia

• chlorpromazine affects many neurotransmitter systems, but its effects on dopamine are the most important for treating psychosis

• antipsychotics work primarily by blocking dopamine receptors, specifically the D2 variety (they are D2 antagonists)

Dopamine’s role in schizophrenia

• the positive symptoms of schizophrenia seem to be caused by excessive stimulation of dopamine D2 receptors in the striatum

• schizophrenia may also involve under-stimulation of dopamine D1 receptors in the prefrontal cortex, called hypofrontality

  • may explain problems with planning, problem solving and high-level reasoning

Explain the glutamate and GABA imbalance

• Glutamate hypofunction: schizophrenia may involve reduced activity of glutamate neurons, linked to cognitive and negative symptoms. Glutamate = Go!

• GABA’s role: GABA (inhibitory) balances excitatory activity from glutamate; disruptions in this balance can contribute to the disorganized thinking and behaviour. GABA = Stop!

Excessive synaptic pruning

abnormal synaptic pruning (removing of extra synapses) in adolescence, influenced by glutamate and immune factors, may underlie schizophrenia’s neurodevelopmental aspects