Schizophrenia and psychosis

Question 1

What do genome wide association studies (GWAS) do?

Answer 1

Genome-wide association studies (GWAS) help scientists identify genes associated with a particular disease (or another trait). This method studies the entire set of DNA (the genome) of a large group of people, searching for small variations, called single nucleotide polymorphisms or SNPs.

Question 2

How are polygenic risk scores calculated in GWAS for schizophrenia?

Answer 2

by taking a blood sample from an individual, extract the DNA, and calculate the sum of pre-defined risk alleles weighted according to each alleles effect on the resepective disorder, get the polygenic risk score. The polygenic risk score – or PRS - is a tool for predicting individual genetic susceptibility to a disorder

Question 3

What are some environmental risk factors for schizophrenia?

Answer 3

-Obstetric Events
-Urban Living
-Migration/ethnic minority
-Childhood adversity
-Adverse life events
-Cannabis Use

Question 4

How does abnormal striatal dopamine give risk to psychotics symptoms?

Answer 4

-we learn and update our beliefs through Prediction Error
-constantly predict what we expect to happen in our environment - but if it doesn’t, this results in surprise
-Dopamine neurones fire to unexpected (surprise) but not to expected events.
-dopamine firing facilitates our learning from experience so that a particular event is remembered with enhanced value
-Unmedicated patients, with early psychosis show increased striatal dopamine and prediction error abnormalities
-increased DA signalling leads to aberrant assignment of
importance (salience) to unimportant stimuli

Question 5

What are Spurious Autobiographical Memories?

Answer 5

-Dopamine-induced increased salience during acute psychosis produces experiences which are perceived as real and are therefore registered as (spurious) autobiographical memories;
-effect of dopamine hyperactivity on hippocampal function enhances their encoding.
-Similar to other memories, these should subsequently undergo assimilation, accommodation, and extinction.
-if the abnormal memories are not replaced by normal experiences during remission they may endure rendering the individual persistently delusional.
-This hypothesis explains why long duration of untreated psychosis prior to onset, or indeed after it, is associated with poor response to antipsychotics.

Question 6

Describe the process of predisposition + acute stress or drug abuse leading to psychosis.
(Howes & Murray Lancet 2014)

Answer 6

1.Predisposition plus acute stress or
drug abuse (reduce stress/drug use)
2.Sensitised dopamine system
3.Dopmaine release
4.Aberrant processing of stimuli (can be treated with CBT-biased cognitive schema)
5.Paranoid interpretation
6.Psychosis

Question 7

What can cause drug induced psychosis?

Answer 7

-Stimulants
-Cannabis

Question 8

What can cause affective psychosis?

Answer 8

-Bipolar
-Depression

Question 9

What are some pathways to psychosis?

Answer 9

-Neuro-developmental pathway
-social adversity pathway
-drug induced
-hormonal
affective

Question 10

What does the neurodevelopment pathway to psychosis entail?

Answer 10

1.Poor premorbid function
2. Minor physical abnormalities and/or neurological soft signs
3.Brain structural abnormalities
4.Negative symptoms and neuropsychological deficit
5.Worse outcome with excess of
treatment resistance

Question 11

What does the social adversity pathway to psychosis include?

Answer 11

-childhood trauma
-migration discrimination
-adverse life events

Question 12

What does the drug induced psychosis pathway include?

Answer 12

1. Higher premorbid IQ.
2. Better premorbid function
3. Earlier onset.
4. More positive symptoms
5. Fewer negative symptoms
6. Worse outcome if continue use.