Genetic explanation

• Concordance rate


  The probability of two people with the same genes getting the same disease
• Concordance rate for schizophrenia

  • Monozygotic (MZ) twins - 42%
  • Dizygotic (DZ) twins - 9%
• Classic family and twin studies suggest that there is a strong argument for the heritability of schizophrenia
• Aim


  To review previous research on the genetic transmission of schizophrenia
• Classic family and twin studies

  • Suggest that there is a strong argument for the heritability of schizophrenia
• Concordance rate


  • Monozygotic (MZ) twins - 42%
  • Dizygotic (DZ) twins - 9%
• Aim


  To review previous research on the genetic transmission of schizophrenia
• There is obviously a heavy genetic input into the onset of schizophrenia
• Concordance rates less than 100% show there must be some interaction with the environment
• Genome


  Complete set of genes or genetic material present in a cell or organism
• Genome-wide association studies (GWAS)


  Comparing genomes of people with and without a diagnosis of schizophrenia to see whether they vary in consistent ways
• Genes


  • Some genes are polymorphic - they come in different forms
• GWAS have helped to identify which versions (alleles) of polymorphic genes are more common in people with schizophrenia
• Genetics of schizophrenia


  Extremely complex
• Thousands of gene variants have been linked to this complex condition
• Affected genes


  • Linked to the many different proteins associated with the development, transportation and breakdown of neurotransmitters such as dopamine
• Inheritance of certain alleles

  May be responsible for neurochemical imbalances associated with schizophrenia
• Known genes involved in schizophrenia

  • COMT
  • DISCI
• COMT gene


  Codes for an enzyme which breaks down neurotransmitters (such as dopamine)
• Cell division


  Whole strands of DNA can become duplicated/even deleted
• Duplication/deletion of DNA strands during cell division causes a 'printing error in the biological manual' and can increase a person's risk of developing schizophrenia
• DiGeorge syndrome


  • A strand of DNA containing 30-40 genes is deleted from chromosome 22, linked to the deletion of a specific gene called COMT
• The absence of COMT could be partially responsible for the complex neurochemical imbalances that seem to underpin the symptoms of schizophrenia
• DISC1 gene


  The 'disrupted in schizophrenia' gene
• The DISC1 gene increases the risk of schizophrenia due to its association with the neurotransmitter GABA
• GABA


  An inhibitory neurotransmitter which helps to regulate activity in neural circuits that communicate via dopamine and glutamate
• An abnormality of the DISC1 gene

  Could increase vulnerability to excess dopaminergic activity and subsequent symptoms of schizophrenia
• COMT gene


  Two versions: Met and Val
• Val allele


  • Decreased dopamine activity in the prefrontal cortex
  • Decreased cognitive performance
  • Slightly elevated risk of schizophrenia
• '+' is supported by research evidence
• Evidence to support


  • Role of genetic factors
  • Dopamine deficiency hypothesis
• Effect of Val allele on cognition

  May be stronger in men with schizophrenia than women
• DISCI gene variant


  Role in schizophrenia
• Research evidence


  • In a large Scottish family with an unusually high rate of schizophrenia, 34 family members carried this gene
• Animal experiments


  • Tightly controlled
  • Findings have greater internal validity
• DISCI gene variant


  May be linked to presynaptic dopamine dysregulation
• A meta-analysis of the findings of 14 animal experiments suggests that this may be linked to the impact of DISCI on presynaptic dopamine dysregulation
• Even if there are a wealth of twin studies to support the role of genetics, the validity of these findings is questionable
• It is assumed that MZ twin pairs living in the same household will be exposed to environmental factors that are similar to pairs of DZ twins, but this is highly unlikely
• As MZ twins are always the same gender, look more similar than DZ twins and are more likely to share similar temperaments, they are likely to be parented more similarly than DZ twins