Neurobiology of psychosis

Question 1

What is relevant in social Hx in relation to schizophrenia?

Answer 1

fam hx of schizophrenia?
2nd trimester viral illness
obstetric probs 
childhood CNS infection 
substance abuse

Question 2

Changes in the brain in schizophrenia

• what 3 changes occur to brain volume?
• Grey matter changes?
• white matter changes?
• what is the neurodevelopment model?

Answer 2

-reduced frontal lobe vol/frontal lobe grey matter and enlarged ventricle volume

-due to reduced arborisation and likely progressive
vol reduction in: temporal cortex, medial temporal lobe

-measured using ‘diffusion tensor imaging’ (DTI):
‘fractional anisotropy’ (FA) in higher numbers = healthy white matter tracts
‘mean diffusivity’ (MD) in higher numbers = less healthy WM tracts
see higher MD and reduced FA

-Environmental risk factors act in utero
children have identifiable impaired behaviour, motor and intellectual development from infancy
disrupted normal cerebral cortical architecture & no gliosis

Question 3

What is the dopamine hypothesis?

-what are the 2 dopamine receptor subtypes?

Answer 3

-Drugs which release dopamine in the brain or D2 receptor agonists produce psychotic state so dopamine receptor antagonists are used to treat schizophrenia
assumed its related to overactivity of dopamine pathways in the brain
NOW THINK:
subcortical dopamine hyperactivity leads to psychosis
Mesocortiyal Dopamine hypoctivity leads to negative & cognitive symptoms

-D1- stimulate cAMP
D2- inhibit Adenylyl Cyclase, Ca channels and open K channels
both occur in limbic and striatal areas

Question 4

How are the following NTs involved?

• Glutamine
• seritonin

Answer 4

• altered NMDA receptor subunit expression

- abnormalities in serotonin 2A binding potential in the frontal cortex index smaller

Question 5

What causes this brain pathology?

Answer 5

gene alterations:
Neuregulin
dysbindin
DISC-1

Question 6

SE of antipsychotics, what clinical occurnaces occur as a result of:

• D2 blockade
• 5HT-2 blockade
• Histamine blockade
• Alpha-arenergic blockade

Answer 6

-Acute dystonic reaction
parkinsonism 
Akathisia (restlessness)
Tardive dyskinesia (delayed, abnormal
involuntary movement)
PRL levels inc

• Metabolic syndrome
• sedation & increased appetite

-postural hypotension
dry eyes, mouth, constipation

Question 7

Clozapine

• used in what?
• Why useful?

Answer 7

• treatment resistant schitzophrenia

- 1st gen, more effective with low propensity for extrapyramidal SEs

Question 8

Clozapine

• used in what?
• Why useful?
• SEs?
• monitoring?

Answer 8

• treatment resistant schitzophrenia
• 1st gen, more effective with low propensity for extrapyramidal SEs

-sedation, weight & metabolic syndrome, hyper salvation
Agranulocytosis
Myocarditis

-Weekly for the first 6 months, then fortnightly, then every 4 weeks