Biological Underpinnings of Psychosis Flashcards
Who started the modern research into Schizophrenia and what did they find?
Tim crow and Eve Johnstone 1976
Those with chronic schizophrenia had
: Larger ventricles
: Less cortical volume
: Cognitive Difficulties
Theory emerged of the Dementia of Dementia praecox: Loss of brain tissue becomes reason for illness
What was the change in theory of Schizophrenia between 1976 to 1987?
That the disorder was Neurodevelopment not Neurodegenerative.
Based on work of Lewis and Murray and Danny Weinberger.
What revived the Neurodegenerative theory in 2005?
The research of Lieberman showing those taking Haloperidol for schizophrenia showed a marked decline in cortical areas. Not shown with Olazapine.
Rene Kahn convinced in his work too
How did Nancy Andreasen show that anti-psychotics may be involved in the reduction of cortical volume?
Through a longitudinal study she showed a relationship between amount of anti-psychotic and decrease in volume. Later partly confirmed through animal studies.
What are some other reasons that a Schizophrenic may have reduced cortical size?
Antipsychotics, other substance abuse, stress and unhealthy lifestyle.
How has the ability to use molecular and genetic testing influenced our understanding of Schizophrenia?
The landmark study of Ripke 2014 showed 108 loci of interest, most prominently chromosome 6 in the HLA region. This showed that Schizophrenia was polygenic and that it had a strong genetic component.
What loci were of interest in the GWAS for Schizophrenia?
DRD2: which is already a known target of antipsychotics.
Glutamate genes: Dopamine release
Neurodevelopmental genes
Immune genes
What is the polygenic risk score and why is it useful in schizophrenia?
It is the summation of all the genetic risks to develop the illness.
It allows us to revaluate behaviours
We can see the relationship between environmental factors: Causal or Independent
What is an alternative to polygenic risk score to Schizophrenia?
Copy number variant:
The deletion or duplication of a string of DNA.
Particularly noticeable in Autism (10-20%).
How are CNV related to Schizophrenia?
Several studies have replicated the work of Tom Walsh 2008:
Continuum of CNV emerges where they cause neurdevelopmental issues:
Learning disability, Autism, and later Schizophrenia.
CNV only accounts for 4% of Schizophrenia, how ever the presence of them can increase risk by 10 fold.
Explain the developmental cascade in schizophrenia?
CNV and Poly genetic risks from birth, leads to subtle cognitive and social deficits, leads to depression and anxiety, leads to paranoid, but at early adulthood, dopamine dysregulation causes problems of salience.
What does dopamine do and what is it’s relationship to prodrome and psychosis?
Dopamine alerts our brain to something of interest.
It is elevated in the striatum in full psychosis, but there is a mix of release in prodrome.
The ones with the highest levels of dopamine are the most likely to go on to develop psychosis. Roughly 25%.
What did Howes et al find in 2011 with regard to ARMS and psychosis?
Using PET scan, most of those that ended up developing psychosis had elevated dopamine.
What studies have shown the risk of cannabis and psychosis and what did they show?
Sweedish conscripts and cannabis in adolescents by Arsenault showed increase risk of cannabis use and risk of schizophrenia. It also showed a 4.5 increased risk to schizophrenia if you use it in your teens.
Various studies show the risk of psychosis is roughly doubled.
What is the increased of risk to psychosis from weed, Spice and skunk?
Skunk: 2 for once a week
3 for weekends, 5.4 for every day.
THC is 16%
Synthetic cannabinoids that have 100% effect on CB1 receptors. Develop psychosis in days.
Weed: Majority of people no risk.
