VC - Depression II

Question 1

What are some causes of depression? (4)

Answer 1

• Genetics: Difficult to pinpoint a single gene.
• Environment: Interaction with the environment is the strongest determinant of expressing a depressive episode.
• Sex differences: Biological differences, with females showing behavioral changes related to hormonal state.
• Defined environment-genetic interaction.

Question 2

What is the role of the stress pathway in depression? (6)

Answer 2

• Stress is a major trigger for depression.
• Dysregulation in feedback inhibition elevates CRF and glucocorticoids in depression.
• Elevated glucocorticoids can kill cells and inhibit synaptogenesis and neurogenesis in the hippocampus.
• CRF receptors (CRF1 and CRF2) also exist outside the hypothalamic-pituitary axis (e.g., amygdala).
• CRF receptor changes have been observed in post-mortem brains of depressed patients.
• CRF receptor antagonists show potential as treatments.

Question 3

What is the Monoamine Theory of Depression? (3)

Answer 3

• Depression is caused by a deficiency or imbalance of neurotransmitters (monoamines) in the brain.
• Increasing neurotransmitter levels can improve mood.
• Monoamines include serotonin, noradrenaline, and dopamine.

Question 4

What role did Iproniazid play in the development of antidepressants? (2)

Answer 4

• Initially used in TB trials, patients reported elevated mood.
• It inhibits monoamine oxidase (MAO), increasing the availability of monoamines.

Question 5

What is the function of MOA? (2)

Answer 5

• MAO-A metabolizes serotonin, noradrenaline, and dopamine
• MAO-B selectively metabolizes dopamine.

Question 6

How does Imipramine work to treat depression? (2)

Answer 6

• Blocks transporters to elevate levels of adrenaline, serotonin, and dopamine.
• Prevents reuptake of neurotransmitters, enhancing signaling efficiency.

Question 7

What is the imipramines relative potency in blocking the reuptake of monoamine?

Answer 7

Adrenalin > serotonin > dopamine

Question 8

What evidence supports the Monoamine Hypothesis? (4)

Answer 8

• Antidepressants that increase monoamine levels or synthesis show efficacy.
• Drugs depleting monoamine storage (e.g. reserpine) or synthesis (e.g. alpha-methyltyrosine) act as mood depressors.
• Alterations in monoamine receptors, such as 5HT 2A, have been observed in depressed patients.
• Elevated metabolites of noradrenaline and serotonin during manic phases suggest a link between monoamine imbalances and mood disorders.

Question 9

What happens when you elevate monoamine levels?

Answer 9

Increases key neurotransmitters across brain regions.

Question 10

Where are the monoamines produced? (3)

Answer 10

• Serotonin is produced in the dorsal raphe and affects various brain structures.
• Dopamine pathways include the ventral tegmentum and substantia nigra.
• Noradrenaline is produced in the locus coeruleus with widespread axonal reach.

Question 11

How do Selective Serotonin Reuptake Inhibitors (SSRIs) work? (3)

Answer 11

• SSRIs prevent monoamines from re-entering cells by occupying binding sites on transporters.
• They increase serotonin, enhancing mood.
• Some SSRIs, like citalopram, may have multiple binding sites (allosteric binding sites).

Question 12

What are NaSSA antidepressants, and what is the mechanism of action?

Answer 12

• They selectively increase noradrenaline and serotonin by blocking certain receptors.

Mechanism of Action:

• Selective increase in Noradrenaline: Achieved through the blockade of autoreceptors.
• Selective increase in Serotonin: Accomplished by blocking heteroreceptors.
• Additional effects: May involve blocking or activating specific sub-classes of receptors.

NaSSAs are used when SSRIs aren’t effective but tend to have more side effects.