Biological underpinnings of psychotic illness Flashcards
When and what was the start of modern research into schizophrenia?
1976: Tim Crow & Eve Johnstone
- first to apply brain scanning to those with schizophrenia
- those with chronic schizophrenia had larger fluid-filled space in centre of brain
- less cortical volume than healthy controls
- cognitive difficulties
What were the thoughts on aetiology of schizophrenia after the scan study of Tim Crow and Eve Johnstone on chronic schizophrenia (1976)?
- Loss of brain tissue
- brain was normal until early adult life and then deteriorated
- > hypothesis of degenerative disorder
What were the thoughts on the aetiology of schizophrenia after the studies of Lewis and Murray (1987) and Danny Weinberger (1987)?
- Developmental problem that increase one’s vulnerability to psychotic symptoms
- Late 90s: developmental hypothesis largely accepted
What were the thoughts on the aetiology of schizophrenia after the studies of Lieberman and colleagues (2005) and Rene Kahn (2006)?
- There’s an intrinsic degeneration in the brain of those with schizophrenia, which was prevented by olanzapine
- Progressive brain disorder, maybe caused by Haloperidol
- schizophrenia patients on haloperidol showed decline in grey matter of the brain compared to controls or those on olanzapine
What did the study led by Nancy Andreasen show on the aetiology of schizophrenia (Ho et al., 2011)?
Longitudinal study of first-episode schizophrenia:
- follow up max 15 years and repeated brain scans
- smallest dose of antipsychotic Chlorpromazine (115mL) showed smaller decrease in cortical volume
- > is it the illness or antipsychotic causing this
- giving animals antipsychotics showed decline in cortex volume
- > decline cause partly by antipsychotics
What do we know now about the aetiology of schizophrenia?
The progressive brain changes in the illness are in part due to:
- antipsychotics
- cannabis and other drugs
- stress and cortisol damage
- lack of exercise
- > not an intrinsic degeneration of the brain
- > improve one’s lifestyle and decrease use of antipsychotics
What was the breakthrough for schizophrenia in molecular genetics?
Genetic component in schizophrenia
- numerous genes involved in the susceptibility of schizophrenia
- 108 areas of genome associated with developing schizophrenia
Ripke et al., 2014: Polygenic dissection of diagnosis and clinical dimensions of bipolar disorder and schizophrenia
- global collaboration (36,989 participants; 113,075 healthy controls)
Which genetic loci impact one’s vulnerability to psychosis?
- Dopamine D2 receptors: antipsychotics
- Glutamate genes: influence dopamine release
- Neurodevelopmental genes
- Immune genes
- > polygenic risk
What is the polygenic risk score?
Calculated by the sum of the involved genetic loci
How could the polygenic risk score of psychosis be used?
- Someone demonstrating signs of psychosis in young age
- > test polygenic risk score
- > take steps to prevent/manage first episode of psychosis
- Examine relationship between genetic factors and environmental risk factors (e.g. cannabis use)
What is the role of the polygenic factor in the onset of schizophrenia?
- Individual risk genes are neither necessary nor sufficient to cause schizophrenia
- > they increase the risk
- Polygenic (small) effects accumulate with environmental factors to increase one’s liability to psychosis
- > threshold of psychosis
- > we all have a level of risk genes for schizophrenia BUT does not mean we’ll development psychosis or schizophrenia
What does it mean that schizophrenia is polygenic?
Requires a combination of gene and environmental factors
What are copy number variants?
‘knock-out genes’
- deletion or duplication of genes resulting in incorrect amount of genes
- if you lose/duplicate a chunk of your DNA and if these are neurodevelopment genes, this will damage the development of your brain
- high proportion (10-20%) of those with autism, learning disability and epilepsy have copy number variant
What is the role of copy number variants in schizophrenia (Walsh et al., 2008)?
Continuum of neurodevelopment impairment with the same copy number variants causing
- learning disability (early)
- then autism
- schizophrenia (late)
- CNVs are rare but dramatically increase your liability (possibly 10 times more likely to develop schizophrenia)
What are the genetics involved in schizophrenia?
- Polygenes (96-97%)
- Copy number variants (3-4%)