schizophrenia - DA and drugs

Question 1

chlorpromazine discovery

Answer 1

first antipsychotic in 1950s as antihistamine and anti-inflammatory

Question 2

DA hypothesis origin

Answer 2

chlorpromazine and reserpine both deplete DA
too much of them make Parkinson’s symptoms develop due to DA loss in nigrostriatal pathway
(rooted in substantia nigra and ventral tegmental areas - extending into limbic region)

Question 3

neural pathways in DA hypothesis

Answer 3

excess DA in mesocorticolimbic pathway (ventral tegmental out into frontal cortex)
recent studies show it to be nigrostriatal pathway instead (substantia nigra into limbic system)

Question 4

reserpine discovery

Answer 4

treatment for mental illness in India
no longer used as it causes decline in blood pressure

Question 5

dopamine levels impact on symptoms

Answer 5

increase DA = increase symptoms

decrease DA = decrease symptoms

specifically increases/decreases action of D2 receptors

Question 6

substances that form dopamine

Answer 6

tyrosine –> L-dopa –> dopamine
in presynaptic

Question 7

specific drug effects on DA (4)

Answer 7

reserpine = depletes vesicles so DA cannot be released as much (also blocking other monoamines)

chlorpromazine = antagonist which binds to and blocks DA receptors

cocaine and amphetamines = cause psychosis and episodes in healthy suers - increases extracellular DA and other monoamines in brain

caffeine = can cause psychosis too

Question 8

anti-psychotic drugs efficacy

Answer 8

correlation with ability to bind to DA receptors

Question 9

haloperidol action

Answer 9

high efficacy for SZ treatment - binds to D2 receptors, not D1 - atypical antipsychotic

Question 10

DA receptors structure - types of DA receptor

Answer 10

G-protein coupled receptors
D1 = positively coupled to adenylate cyclase
D2 = negatively coupled to adenylate cyclase

two families (D1 and D2 like)
D1 = D1&5
D2 = D2,3,4

Question 11

atypical antipsychotics

Answer 11

clozapine - D1 and D4 blocking, slightly blocks on D2, blocks several serotonin and histamine receptors (less motor side effects

aripiprazole, respiridone, quetiapine

Question 12

phenothiazines

Answer 12

chemical class which binds to D1 and D2 - e.g. chlorpromazine

Question 13

butyrophenones

Answer 13

chemical class - binds to D2 NOT D1 - e.g. haloperidol

Question 14

what does the D2 theory of SZ not explain

Answer 14

blocking occurs within hours of taking drugs but effects take 2-3 weeks
most antipsychotics treat positive symptoms, not negative

Question 15

psychedelic drug treatment of SZ

Answer 15

psychedelic effects mimic positive symptoms of SZ - agonist of serotonin 2a receptor
dissociative hallucinogens (ket) mimic negative symptoms - glutamate receptor antagonist

Question 16

study of DA theory

Answer 16

reserpine used to lower extracellular DA levels
IBZM used as a radioactive chemical which binds to DA receptors to see number of DA receptors in SZ vs control participants
evidence for overactive DA in some people with SZ

Question 17

what are CNVs

Answer 17

copy number variants
deletions and duplications in parts of chromosomes - therefore certain genes are missing
2 copies or no copies can have the same effect

Question 18

CNVs with ASD and SZ

Answer 18

16p = chromosome region where CNVs are linked to both ASD an SZ - some of these genes are related to DA

Question 19

brain structure differences in SZ

Answer 19

enlarged ventricles
grey matter loss (and some white) in cortical regions
temporal lobe degeneration
smaller cortex and hippocampus

Question 20

hippocampus link with SZ

Answer 20

those at risk (e.g. have close relative with SZ) have volume reduction in brain areas such as hippocampus

Question 21

brain differences in SZ and when it occurs

Answer 21

brain differences already exist when patients first seek treatment and these changes continue to develop after diagnosis - can’t determine causality direction

alterations to brain areas occur at different rates

Question 22

Thompson study of grey matter and SZ

Answer 22

12 people with childhood onset SZ (COS)
longitudinal MRI study of grey matter, compared with 12 controls
loss in parietal, motor, and temporal cortices
deficits move in dynamic pattern as more cortex is enveloped throughout adolescence
first loss in parietal (visuospatial and associative thinking)
progresses anteriorly to temporal lobes (sensorimotor, dorsolateral prefrontal cortices, frontal eye fields)
these losses mirror symptoms related to area with loss