T3L3 schizophrenia neurobiology

Question 1

aetiology- causes

Answer 1

genetic risk

• 1% general population
• 50% monozygotic twin

interaction of genes and environment
polygenic

Question 2

genes and environement

Answer 2

genetic pruning during puberty&raquo_space; brain maturation

environment:

• birth > prenatal infection, nutritional deficiency, obs complications
• adolescence > adverse life events, substance abuse

Question 3

neuropathology

Answer 3

• ventricular enlargement
• reduced grey matter - temporal and frontal lobes, subcortical structures
• cell differences in cortex and hippocampus

neurophysiology:
hypofrontality during periods of high cognitive load

differences in neural oscillations and synchrony

Question 4

age of presentation m and f

Answer 4

m 20-28

f 26-31

Question 5

neurodevelopment of schizophrenia

Answer 5

• proliferation, migration, arborization (circuit formation)
  and myelination
• in schizophrenia, overpruning of weak circuits leads to decrease grey matter
• decreased excitatory synapse strength and increase inhibitory strength
• leads to increase excitatory pruning
• somehow leads to hyper-excitable sensory cortex

Question 6

psychopharmacology

Answer 6

1) typical antipsychotic
- D2 receptor antagonist
- prevents positive symptoms
- eg haloperidol
- side effects eg slow movement, lack of expression

2) DA agonists
- eg clozapine
- increase DA activity in PFC
- decrease DA in NAcc
- improves +ve and -ve symptoms
- side effects are psychotic state, weight gain, sedation

atypicals can work in patients resistant to typicals

learn S29

Question 7

5 dopamine receptors

Answer 7

1. Gs coupled receptors
   D1- caudate-putamen
   D5 - hypothalamus, hippocampus, NAcc
2. Gi coupled receptors
   D2- caudate-putamen-NAcc
   D3- hypothalamus, NAcc, cerebellum
   D4- frontal cortex, medulla, amygdala

Question 8

NAcc stands for

Answer 8

nucleus accumbens

Question 9

glutamate hypothesis evidence

Answer 9

PCP is a NMDA Receptor antagonist
- emulates schizophrenia

NMDA blocked
»
less glutamatergic firing to VTA GABA neurons
»
less GABAergic inhibition of VTA-NAcc DA neurons
»
greater DA release in NAcc
»
less activation of VTA-PFC neurons&raquo_space; less glu&raquo_space; hypofrontality

Question 10

VTA stands for

Answer 10

ventral tegmental area

Question 11

symptoms these drugs cant help

Answer 11

• lower iq
• attentional deficits
• working memory
• planning and info processing