Neuronal changes in depression: role of growth factors, adult neurogenesis, and neuroplasticity

Question 1

What are the limitations of the monoamine hypothesis?

Answer 1

• it does not explain the onset of action (>/= 2 weeks before any significant effect)
• no mechanistic links between the monoamine system(s) and depression
• non responders (</= 60 % of patients will respond to monoamine antidepressents)

Question 2

Explain how the clinical effects of antidepressants were different from placebo.

Answer 2

• Followed the same trend (decrease in HAMD score), but the antidepressant group showed a significant higher level of decrease
• The placebo group would go back up after a while, antidepressent group not (?)

Question 3

Describe the problem with antidepressents targeting the 5-ht-1A receptor.

Answer 3

Serotonine is an autoinhibitor, meaning it will inhibit the neuron of origin through the 5-HT-1A receptor
- will the inhibition of 5-HT-1A on the presynaptic neuron have therapeutic effects? –> no
- will the inhibition of 5-HT-1A on the postsynaptic neuron have any negative effects? –> no

Question 4

What is SSRI?

Answer 4

Selective serotonine reuptake inhibitor - an antidepressent

Question 5

What is the biggest bias in the current research on the area of how depression is affecting the size of the hippocampus?

Answer 5

Most of these studies are done in people with severe MDD.

Question 6

Briefly explain the dynamic theory.

Answer 6

Based on both pharmaco-, electroconvulsive- and psychotherapy

Question 7

What is BDNF and what is its function?

Answer 7

• brain derived neurotrophic factor
• binds to TrkB –> neuronal differentiation, survival and synaptic plasticity
• binds to p75NTR –> apoptosis/LTD/growth cone reaction
• the precursor proBDNF also have some functions

Question 8

What is the Y433 residue responsible for?

Answer 8

Essential for binding of both antidepressents and psychedelics

Question 9

How does a single does of psilocybin affect patients with depression?

Answer 9

Elicit a significant reduction in depression score after only 2 days

Question 10

What binds with a higher affinity - antidepressents or psychedelics?

Answer 10

Psychedelics

Question 11

Does SSRI and psilocybin bind to the same site in the TMD of TrkB?

Answer 11

No, they bind to distinct sites