Psychosis: what is the neurobiological basis?

Question 1

What is neurodevelopmental hypothesis?

Answer 1

There are brain strcutural abnormalities among people with schizophrenia (less grey matter volume, enlarge ventricles in the brain etc) which could be explained by pathological development at birth and then struggle to ‘catch up’ HOWEVER, it’s difficult to say if its neurodevelopemtnal or neurodegenerative

Question 2

What is neurodegenerative hypothesis?

Answer 2

Prospective studies showing an overall decrease in gray matter among people with schizophrenia

• This can be due to the disorder itself, environmetnal factors relative to having schiozophrenia, effect of medication
  (could be that those who take them are also more severe?)

Longer relapse linked to greater loss cerebral volume

Question 3

What are the limitations to both neurodevelopmental and neurodegenerative hypotheses?

Answer 3

1. Brain structural differences at onset of illness and in prodrome support neurodevelopmental hypothesis

But are these secondary to symptoms?

2. Further brain changes after the onset of illness support the neurodegenerative hypothesis

But could these be due to other factors?
Stress? Cannabis? Antipsychotic treatment?

Question 4

Glutamatergic hypotheses

Answer 4

1. Katamine can induce psychosis and negative symptoms and katamine increases Gluatamate in prefrotnal cortex
2. Schizophrenia is associated with elevations in glutamatergic metabolites across several brain regions.

Question 5

What is glutamate?

Answer 5

Glutamate is recognized as the most abundant excitatory amino acid neurotransmitter in the brain.

NMDR is a glutamate receptor in the brain

Question 6

Limitation to glutamate hypothesis

Answer 6

How do glutamatergic abnormalities lead to symptoms?

No drugs targeting glutamate yet licensed

Question 7

Dopamine hypothesis

Answer 7

Support also given by antipsychotics working on D2 receptor inhibition with decrease in positive symptoms = reducing dopamine decreases symptoms AND amphetamines make psychosis symptoms worse

+ there is evidecene for stress-induces dopamine synthesis and ppl with psychosis experience more stress

+ aberrant salience
+ the stratala and frontal dopamine release relationship

Question 8

Intergraded hypothesis

Answer 8

Integrates dopamine and glutamate hypothesis

There is some (only beginning idea of evidence) that there can be ketamine-induced elevation in striatal dopamine synthesis capacity which woud link the 2 hypothesies together
Kokkinou et al 2022

Question 9

Limitations to dopamine hypothesis

Answer 9

1. Link to cognitive and negative symptoms not so well established
2. What about treatment resistance?