Biological explanations for Schizophrenia

• Sz runs in families
  • Weak link in itself as family share many aspects of environment.
  • Systematic investigations of the extent to which greater genetic similarity of family members is associated with greater risk of SZ.
  • Gottesman's large-scale family study (1991)

• Candidate genes
  • Individual genes believed to be associated with risk of inheritance.
  • SZ is polygenic - a number of genes confer a small increased risk.
  • SZ is aetiologically heterogenous - different studies have identified different candidate genes.
  • Ripke et al.
    • Large study combining previous data from genome-wide studies.
    • Genetic makeup of 37,000 patients compared with 113,000 controls.
    • 108 separate variations associated with increased risk of SZ.
    • Associated genes incloded those coding for a number of neurotransmitters (including dopamine).

• Neurotransmitters
  • Appear to work differently in the brain of SZ patient.
  • Dopamine widely believed to be involved.
  • Dopamine important in the functioning of several brain systems that may be implicated in SZ symptoms.
• Hyperdopaminergia in the subcortex
  • Original dopamine hypothesis focused on possible role of high levels in the subcortex.
  • Excess of dopamine receptors in Broca's area (responsible for speech production) may be associated with speech poverty and/or auditory hallucinations.
• Hypodopaminergia in the cortex
  • More recent versions of the dopamine hypothesis have focused on abnormal dopamine systems in cortex.
  • Goldman-Rakic et al. have identified a role for low levels of dopamine in negative symptoms of SZ.
  • May be that both are correct explanations.

• Neural correlates of negative symptoms
  • Avolition involves loss of motivation.
  • Motivation involves anticipation of a reward - ventral striatum.
  • Follows that abnormality of areas like the ventral striatum may be involved in the development of avolition.
  • Juckel et al.
    • Measured activity levels in the ventral striatum in SZ and found lower activity than those observed in controls.
    • Negative correlation between activity levels in VS and the severity of overall symptoms.
• Neural correlates of positive symptoms
  • Allen et al.
    • Scanned the brains of patients experiencing auditory hallucinations and compared them to a control group whilst they identified pre-recorded speech as theirs or others.
    • Lower activation levels in the superior temporal gyrus and anterior cingulate gyrus were found in hallucination group (also made more errors).

• Gottesman study
  • Clearly shows how genetic similarity and shared risk of SZ are closely related.
• Adoption studies (Tienari et al.)
  • Children of SZ sufferers are still at heightened risk of SZ if adopted into families with no history of SZ.
• Also evidence from studies conducted at a molecular level that particular genetic variations increase the risk of SZ (Ripke et al.)

• Dopamine agonists like amphetamines that increase levels of dopamine make SZ worse and can produce SZ-like symptoms in non-sufferers (Curran et al.)
• Antipsychotic drugs work by reducing dopamine activity (Tauscher et al.).
• Both drugs suggest an important role for dopamine.
• Radioactive labelling studies (Lindstroem et al.) have found that chemicals needed to produce dopamine are taken up faster in the brains of SZ than controls. (Suggests that they produce more dopamine)
• Some of the genes identified by Ripke et al. also code for the production of other neurotransmitters.
• Glutamate (Moghaddam and Javitt) - shift focused.

• Evidence leaves important questions unanswered.
• Does the unusual activity cause the symptom or does the symptom cause the unusual activity?
• May be that something wrong in the ventral striatum is causing negative symptoms.
• Also possible that negative symptoms means less information passes through the striatum, resulting in reduced activity.
• May be both factors.

• Can take place in absence of family history.
• Mutation in parental DNA.
• Can be caused by radiation, poison or viral infection.
• Evidence from study showing positive correlation between paternal age (associated with increased risk of sperm mutation) and a risk of SZ.
• Increasing from around 0.7% with fathers under 25 to over 2% in fathers over 50 (Brown et al.)

The role of psychological environment is important but unclear

• Evidence supporting biological factors is overwhelming
• Also evidence to suggest an important role for environmental factors (including psychological).