New evidence for antidepressant function

John

You may or may not know that all antidepressants show a delay in the onset of their therapeutic functions. For example fluoxetine can take 3-5 weeks to have an antidepressant effect. A few theories were thrown about as to why this was (autoreceptor downregulation, neurotrophin upregulation, synaptogenesis, neurogenesis, etc). New research (which I think is exciting) shows that fluoxetine acts specifically a subset of cells that will develop into neurons in the dentate gyrus (which is more associated with memory rather than mood). This provides a platform for research into new drugs that will bypass the side effects of traditional antidepressants and hopefully provide a shorter onset of therapeutic action (although I'm sceptical that it will be instant). Whether or not it leads to further insights in antidepressants is a side issue for me but I'd be interested to see if it explains anything about memory.

Link to PubMed

Link to BBC

InFront

John wrote:

fluoxetine acts specifically a subset of cells that will develop into neurons in the dentate gyrus (which is more associated with memory rather than mood). This provides a platform for research into new drugs that will bypass the side effects of traditional antidepressants and hopefully provide a shorter onset of therapeutic action (although I'm sceptical that it will be instant)

Very interesting stuff, I just have a question about one aspect of it;

How can they hope to quicken the process of neurogenesis, presumably it is the 5-HT uptake inhibition that is causing the secondary adaptive response over a period of time?
How can they hope to get the desired result without sitting on their hands for this time while the hippocampus (or the dentate gyrus) to 'wake up' to this inhibition, and decide to do something about ANPs/ neurogenesis? Is a more potent drug really likely to shorten the time period required?

What I mean is, the biochemical action isn't the issue, it's the brain's method of responding and 'giving a reply'.

DrIndy

Zyprexa = olanzapine

It is known to occasionally cause stroke as a side effect.

Olanzapine is not an antidepressant, but an atypical anti-psychotic and is rarely used now.

John

InFront wrote:

How can they hope to quicken the process of neurogenesis, presumably it is the 5-HT uptake inhibition that is causing the secondary adaptive response over a period of time?

I don't think anyone hopes to quicken the process of neurogenesis. It isn't even clear any more if neurogenesis is the case at all. I was at a symposium on hippocampal neurogenesis a couple of weeks ago in England where there was some research presented which cast some doubt on SSRIs causing an antidepressant effect via neurogenesis. (Which asks the question, if it isn't directly an increase in 5-HT concentrations nor neurogenesis, what the hell is it?)

How can they hope to get the desired result without sitting on their hands for this time while the hippocampus (or the dentate gyrus) to 'wake up' to this inhibition, and decide to do something about ANPs/ neurogenesis? Is a more potent drug really likely to shorten the time period required?

What I mean is, the biochemical action isn't the issue, it's the brain's method of responding and 'giving a reply'.

The other thing to consider is that the dentate gyrus is highly plastic. A short burst of electrical stimulation gets the neurons there undergoing neurogenesis (which is relatively slow) and synaptogenesis (which is faster). It may not be an increase in the number of neurons but an enhancement in connectivity via synaptogenesis, i.e. existing cells making more connections with each other.

By the way, I don't remember posting this thread at all. *looks at date* Ah, nearly a year old, that's why.

InFront

Ha, I didn't spot the dates either.

It isn't even clear any more if neurogenesis is the case at all. I was at a symposium on hippocampal neurogenesis a couple of weeks ago in England where there was some research presented which cast some doubt on SSRIs causing an antidepressant effect via neurogenesis. (Which asks the question, if it isn't directly an increase in 5-HT concentrations nor neurogenesis, what the hell is it?)

Yes it sort of brings everything back to step 1. But I presume that even in light of that research, neurogenesis (or indeed synaptogenesis) would nevertheless be considered the most plausible explanations for SSRI action, would that be accurate?

nesf

DrIndy wrote:

Zyprexa = olanzapine

It is known to occasionally cause stroke as a side effect.

Olanzapine is not an antidepressant, but an atypical anti-psychotic and is rarely used now.

It is also used as a mood stabiliser and it is prescribed still by some doctors. It's not a very nice drug but apparently it is very effective. The high weight gain on it and the potential for drug induced Parkinsons is problematic in its use though.

2Scoops

Where did the other posts go?

simu

You were posting potentially libellous material. Do so again and you'll be banned.

DrIndy

God! Look away for a day and all this happens!

LadyJane - please don't post any more on this matter. What you are stating is inflammatory and possibly libellous. Sending the same information via PM does not obviate anything.

Banned from this forum.