Pathology and Treatment

Question 1

What happens if there’s increased mesolimbic dopamine transmission?

Answer 1

Positive symptoms can occur

Question 2

What are examples of positive symptoms?

Answer 2

Experiencing something that isn’t in the world around you (you basically add so + stuff into your brain)

• delusions
• hallucinations (auditory or visual)
• thought interference

Question 3

What are examples of negative symptoms?

Answer 3

An absence or something missing
(Withdrawn so negative)
- no emotion (blunted affect)
- decreased motivation 
- social withdrawal
- poverty of speech (using very few words)

Question 4

What are the dopaminergic pathways thought to be involved in psychosis?

Answer 4

Mesolimbic - VTA increased dopamine release to NA = positive symptoms
Mesocortical - VTA decreased release dopamine to PFC = negative symptoms
Nigrostriatal pathway = dopamine increase leads to dyskinesia and decrease leads to dystonia
Tuberofinundibular = inhibits prolactin release

Question 5

What causes extrapyramidal effects (movement disorders)?

Answer 5

Dopaminergic antagonist can’t selectively bind to specific pathway.
Long term antagonism of nigrostriatal pathway = D2 receptors become more sensitive

Question 6

Why do you see a wide range of side effects in low-potency first generation antipsychotics?

Answer 6

Low affinity for D2 receptor = bind to alpha-adrenergic, muscarinic, 5HT2c, histamine receptors = wide range of side effects

Question 7

How does the serotonergic system play a role in psychosis?

Answer 7

Increase serotonin levels = decrease dopamine levels = increased positive and negative symptoms

Question 8

How does glutamate play a role in psychosis?

Answer 8

Increased glutamatergic levels may be involved in treatment resistance as can induce positive and negative symptoms

Question 9

Which antipsychotic is used for treatment resistant schizophrenia?

Answer 9

Clozapine = has combined serotonergic and dopaminergic action therefore more effective

Question 10

MoA of typical antipsychotics

Answer 10

D2 receptor antagonism - non-selective for any of the 4 dopamine pathways

Question 11

MoA of atypical antipsychotics?

Answer 11

D2 and 5HT-2a receptor antagonism
Serotonin usually inhibits dopamine release so if you block 5HT-2a then dopamine levels increase = better negative symptom effects
Occupy D2 receptors transiently and dissociate slowly = allows relatively normal DA neurotransmission

Question 12

T/F atypical antipsychotics are more selective for the D2 receptors in the mesocortical pathway

Answer 12

False - they are more selective for the D2 receptors in the mesolimbic pathway

Question 13

What are the subclasses of typical antipsychotics?

Answer 13

High potency and low potency

Question 14

How should you treat a patient who is non-compliant with their medication?

Answer 14

Long acting injections = reduced chance of relapse as compliance won’t be an issue = delivers the drug slowly over weeks/months

Question 15

How can smoking effect certain antipsychotics?

Answer 15

Can alter the level of clozapine in the body = making it less effective
Abruptly stopping smoking = levels of clozapine will increase rapidly leading to toxicity

Question 16

Which part of the brain region is responsible for positive symptoms?

Answer 16

Mesolimbic pathway (VTA-NA)

Question 17

Which region of the brain affected is responsible for negative symptoms?

Answer 17

Mesocortical pathway (VTA-PFC) 
- if this pathway is under active we expect to see a rise in negative symptoms

Question 18

Which brain region is responsible for the extrapyramidal effects seen in patients with schizophrenia?

Answer 18

Nigrostriatal pathway

- long term down regulation = increased activity of D2 in striatum = increased EPS