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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 2 to 26 of 26. Go back in thread:
Posted by saturn on May 27, 2006, at 9:51:14
In reply to one thing Prozac does, not chemical imbalance, posted by Larry Hoover on May 27, 2006, at 8:59:53
Interesting article, Lar.Is increased serotonin the stimulus for the production of the ANP's?
Posted by SLS on May 27, 2006, at 10:06:23
In reply to one thing Prozac does, not chemical imbalance, posted by Larry Hoover on May 27, 2006, at 8:59:53
> http://news.bbc.co.uk/1/hi/health/4771777.stm
>
> It's not in Pubmed yet.
>
> Lar
I wish they were more specific regarding the chain of events leading up to the production of these progenitor cells. Does the drug bind to a cytosolic protein or a nucleic gene regulator, or is it the result of repeated action potentials produced by the 5-HT reuptake inhibition? In other words, is this neural generation an effect secondary to the resolution of depression or is it the primary resolution of the depression itself?I'm not expressing myself very well. Some of the verbiage in the article hints that the proliferation of cells seen in the dentate gyrus is the result of increased electrical activity. This by itself explains nothing. It is more of an observed consequence of exposure to Prozac rather than an explanation for the cascade of events leading up to it.
"If a drug fosters electrical activity in the brain, that tells the brain that things are happening and that it might be good to make new neurons to deal with activity."
I wish we could read the full text of the article to be published.
- Scott
Posted by Larry Hoover on May 27, 2006, at 12:14:29
In reply to Re: one thing Prozac does, not chemical imbalance, posted by SLS on May 27, 2006, at 10:06:23
> I wish we could read the full text of the article to be published.
>
>
> - ScottIt's in one of the Annals, if I recall correctly, and I'm not sure if they even publish abstracts.
Yes, the full text would be very nice. Maybe somebody could accidentally post it?
Lar
Posted by djmmm on May 27, 2006, at 14:44:11
In reply to one thing Prozac does, not chemical imbalance, posted by Larry Hoover on May 27, 2006, at 8:59:53
> http://news.bbc.co.uk/1/hi/health/4771777.stm
>
> It's not in Pubmed yet.
>
> LarThey published something on this in the NewScientist
http://www.dr-bob.org/babble/20060515/msgs/644661.htmlhttp://www.newscientist.com/article/dn9171-how-prozac-affects-the-brain.html
here is the abstract:
Fluoxetine targets early progenitor cells in the adult brain
Juan M. Encinas, Anne Vaahtokari, and Grigori Enikolopov*
Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724
Communicated by James D. Watson, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, March 15, 2006 (received for review January 19, 2006)
Chronic treatment with antidepressants increases neurogenesis in the adult hippocampus. This increase in the production of new neurons may be required for the behavioral effects of antidepressants. However, it is not known which class of cells within the neuronal differentiation cascade is targeted by the drugs. We have generated a reporter mouse line, which allows identification and classification of early neuronal progenitors. It also allows accurate quantitation of changes induced by neurogenic agents in these distinct subclasses of neuronal precursors. We use this line to demonstrate that the selective serotonin reuptake inhibitor antidepressant fluoxetine does not affect division of stem-like cells in the dentate gyrus but increases symmetric divisions of an early progenitor cell class. We further demonstrate that these cells are the sole class of neuronal progenitors targeted by fluoxetine in the adult brain and suggest that the fluoxetine-induced increase in new neurons arises as a result of the expansion of this cell class. This finding defines a cellular target for antidepressant drug therapies.
Posted by Phillipa on May 27, 2006, at 15:10:41
In reply to Re: one thing Prozac does, not chemical imbalance, posted by djmmm on May 27, 2006, at 14:44:11
Could someone explain this in English that a novice like me can understand as I have no idea what the articles is saying. Love Phillipa
Posted by linkadge on May 27, 2006, at 15:58:21
In reply to Re: one thing Prozac does, not chemical imbalance, posted by Phillipa on May 27, 2006, at 15:10:41
Correct me if I'm wrong, but doesn't certain forms of neurogenesis also depend on norepinephrine and dopamine signalling?
As long as a ballence is not lost, else you may be supressing growth in other regions of the brain.
Linkadge
Posted by linkadge on May 27, 2006, at 15:59:32
In reply to Re: one thing Prozac does, not chemical imbalance, posted by Phillipa on May 27, 2006, at 15:10:41
There are other neurotrophic compounds available. I believe that mice lacking the cannabanoid receptors have impaired forms of neurogenesis. Marajuanna derivitives probably promote neurogenesis though the cannabanoid CB1 receptor.
Linkadge
Posted by bassman on May 28, 2006, at 12:47:38
In reply to one thing Prozac does, not chemical imbalance, posted by Larry Hoover on May 27, 2006, at 8:59:53
One thing to note, of course, is that the study was in mice. When drugs worked in a certain way in mice (also rabbit, ferret, dog, etc.), but not in humans (which happened very frequently)-I would ask the pharmacologists that did the study why that might be. There answer was always the same, and very profound: "people aren't mice". :>} I wish I had a dime for every anticancer drug that has worked magnificantly in mice and didn't do anything but make people sick. Anyway, the article is interesting and sort of supports and presents a mechanism for(do you agree?) the idea that depression is a progressive disease.
Posted by Larry Hoover on May 28, 2006, at 17:44:33
In reply to Re: one thing Prozac does, not chemical imbalance, posted by bassman on May 28, 2006, at 12:47:38
> One thing to note, of course, is that the study was in mice. When drugs worked in a certain way in mice (also rabbit, ferret, dog, etc.), but not in humans (which happened very frequently)-I would ask the pharmacologists that did the study why that might be. There answer was always the same, and very profound: "people aren't mice". :>}
Bang on, mate. Or the study that showed that Prozac corkscrewed neurons or receptors or whatever it was. The dose was only 110 times the human dose. Toxic threshold ring any bells?
> I wish I had a dime for every anticancer drug that has worked magnificantly in mice and didn't do anything but make people sick. Anyway, the article is interesting and sort of supports and presents a mechanism for(do you agree?) the idea that depression is a progressive disease.
Yes, it is a progressive disease, if untreated. The trick is the unleashing of the repair mechanisms. Talk therapy must do something similar, wouldn't you think? It has similar efficacy. And the combination is synergistic.
I still haven't read that full-text link. Might be something neat in there, nonetheless.
Lar
Posted by Larry Hoover on May 28, 2006, at 17:45:19
In reply to Re: one thing Prozac does, not chemical imbalance, posted by djmmm on May 27, 2006, at 14:44:11
Posted by bassman on May 28, 2006, at 18:21:09
In reply to Re: one thing Prozac does, not chemical imbalance » bassman, posted by Larry Hoover on May 28, 2006, at 17:44:33
I just don't see how talk therapy can cause changes in the brain or repair or anything. Maybe that happens all the time, with lots of things (eating pizza, interesting aromas, pretty women, being scared, etc.), we just aren't used to thinking that way. I can see how exercise can be a powerful antidepressant-but talk therapy? And yet I know, firsthand, that talk therapy works-at least for depression. I had no luck with it decreasing anxiety. I like the idea of Prozac as sort of a RapidGrow for the brain. :>} Wouldn't it be funny if the "neurotransmitter hypothesis" was dead wrong and AD's just produce/repair brain cells or some other mechanism? Considering all the things that the medical community was Absolutely Sure about for years that have turned out to be Absolutely False, it may be time for a little skepticism for any "certainty"...
Posted by linkadge on May 29, 2006, at 20:14:15
In reply to Re: one thing Prozac does, not chemical imbalance » bassman, posted by Larry Hoover on May 28, 2006, at 17:44:33
>The dose was only 110 times the human dose
I think that study tested several doses, one showed corscrewed receptors at lower doses as well.
The thing about this study was that the changes happenened in mice within a very short period of time. The researchers were questioning whether lower doses for longer periods of time might have the same effect.
Linkadge
Posted by linkadge on May 29, 2006, at 20:27:53
In reply to Re: one thing Prozac does, not chemical imbalance, posted by bassman on May 28, 2006, at 18:21:09
Some researchers have refered to antidepressants as "mental steroids". Oftentimes bodybuilders who use regular steriods can make some pretty significant gains, but it all deflates like a balloon once the steroids are stopped.
So the question as to whether there are any long term, or lasting improvements remains to be seen. Can the circutry function once the sea of serotonin dries up?
My withdrawl from SSRI's seemed like the equal but opposite reaction to every and any positive experience I had felt.
As far as talk therapy goes, I do think it can have a strong effect. Social interaction increases BDNF, which can support the growth of new brain cells. Depression is often about solving problems. Just the act of discussing your problems with other people is theraputic. Thats why many of us are here. If in therapy, you can learn just one technique that can circumvent even just one surge of stress hormone, then you may save a few neurons.
Some studies show that a person who is married is much more likely to experience a full recovery from depression. So, I think it comes down to support. Support can reduce the feelings of helplessness.
Linkadge
Posted by Larry Hoover on May 29, 2006, at 20:40:51
In reply to Re: one thing Prozac does, not chemical imbalance » Larry Hoover, posted by linkadge on May 29, 2006, at 20:14:15
> The researchers were questioning whether lower doses for longer periods of time might have the same effect.
>
> LinkadgeForcing a straight line through the origin, from extreme data points, in other words, absent any evidence of linear dose-response curve, or the absence of a toxic threshold.
Precisely why I question the implications, as the corollary assumptions themselves have not been shown to be applicable.
Lar
Posted by Larry Hoover on May 29, 2006, at 21:27:48
In reply to Re: one thing Prozac does, not chemical imbalance » Larry Hoover, posted by linkadge on May 29, 2006, at 20:14:15
> >The dose was only 110 times the human dose
>
> I think that study tested several doses, one showed corscrewed receptors at lower doses as well.I don't think that's the case. I just looked and found one article, Kalia et al, (2000). She remarked, at the time, that she planned to do follow-up reasearch in which she would "reduce the dose to a much lower one, only 10 to 30 times the normal human dose...." and observe rats for 6 months to a year before examining their brains.
As the original was published in 2000, and no follow-up has yet been published, what can we conjecture from that? I reiterate, the preliminary research was done at doses at least two orders of magnitude greater than that to which humans are exposed. Do that with table salt, and you've got a dead rat.
> The thing about this study was that the changes happenened in mice within a very short period of time.
Brains are not time machines.
> The researchers were questioning whether lower doses for longer periods of time might have the same effect.
>
> LinkadgeI thought I'd found a link to the full-text, but the link was broken and I can only read the first page. http://www.maps.org/publications/2000_kalia_1.pdf
Anybody got another?
Lar
Posted by linkadge on May 30, 2006, at 20:04:18
In reply to Re: one thing Prozac does, not chemical imbalance » linkadge, posted by Larry Hoover on May 29, 2006, at 20:40:51
A lot of these studies simply raise questions. We need more research to clarify.
Linkadge
Posted by linkadge on May 30, 2006, at 20:05:14
In reply to Re: one thing Prozac does, not chemical imbalance » linkadge, posted by Larry Hoover on May 29, 2006, at 21:27:48
I was under the impression that does of 50 and 100 times the human doese produced toxic results in a few days.
Linkadge
Posted by Larry Hoover on May 30, 2006, at 21:40:07
In reply to Re: one thing Prozac does, not chemical imbalance » Larry Hoover, posted by linkadge on May 30, 2006, at 20:05:14
> I was under the impression that does of 50 and 100 times the human doese produced toxic results in a few days.
>
> LinkadgeAnd that tells us what, exactly? I have never heard of a human being overdosing on the same drug, to that extent, for a few days in a row.
And, the article did not demonstrate that morphological change was indicative of damage. That was yet another of the assumptions made. An a priori assumption. Talk about petitio principii (begging the question), this is a classic case of it.
Just to put it into an absurd context, you do that same experiment with water, once, and you'd not be around for day 2. These rats survived the fluoxetine exposure. One could argue that fluoxetine is safer than water.
I wouldn't argue that, but you do have to consider what has been demonstrated by this *preliminary* study, from which follow-up work was supposed to take place, and seemingly never did. Nothing to publish?
It raised questions, but didn't answer one.
Lar
Posted by bassman on May 31, 2006, at 6:21:35
In reply to Re: one thing Prozac does, not chemical imbalance » linkadge, posted by Larry Hoover on May 30, 2006, at 21:40:07
That's so funny-I thought of the analogy with water, too! From taking large "doses" of water and people getting either very sick or dying, we would conclude that water taken in lower volumes over extended times was very dangerous. Maybe bottled water should contain a black box stating, "Caution! The Surgeon General has determined that the consumption of water..." That would be a rival for McDonald's having to put a warning on their coffee cups that the liquid inside might be hot and you shouldn't pour it all over yourself-or plastic bags that state the plastic bags aren't toys. If we could bottle common sense...
Posted by Larry Hoover on May 31, 2006, at 9:41:02
In reply to Re: one thing Prozac does, not chemical imbalance, posted by bassman on May 31, 2006, at 6:21:35
Posted by bassman on May 31, 2006, at 12:52:54
In reply to Re: one thing Prozac does, not chemical imbalance » bassman, posted by Larry Hoover on May 31, 2006, at 9:41:02
Lar-that was wonderful! Damn, every word was true. That darned dihydrogen monoxide-now comes the tricky part: if you sent that link to 100,000 Americans and then determined what percent actually fell for it, what would that percentage be?
Posted by Larry Hoover on May 31, 2006, at 15:24:39
In reply to Re: one thing Prozac does, not chemical imbalance, posted by bassman on May 31, 2006, at 12:52:54
> Lar-that was wonderful! Damn, every word was true. That darned dihydrogen monoxide-now comes the tricky part: if you sent that link to 100,000 Americans and then determined what percent actually fell for it, what would that percentage be?
No less than 75%. Some people do catch on.
Lar
Posted by bassman on May 31, 2006, at 17:48:40
In reply to Re: one thing Prozac does, not chemical imbalance » bassman, posted by Larry Hoover on May 31, 2006, at 15:24:39
You're scaring me...that many?
Posted by Caedmon on June 3, 2006, at 13:04:57
In reply to Re: one thing Prozac does, not chemical imbalance » linkadge, posted by Larry Hoover on May 30, 2006, at 21:40:07
> > I was under the impression that does of 50 and 100 times the human doese produced toxic results in a few days.
> >
> > Linkadge
>
> And that tells us what, exactly? I have never heard of a human being overdosing on the same drug, to that extent, for a few days in a row.
>
> And, the article did not demonstrate that morphological change was indicative of damage. That was yet another of the assumptions made. An a priori assumption. Talk about petitio principii (begging the question), this is a classic case of it.>
Lar,I quite agree with your assessment.
- Chris
Posted by Larry Hoover on June 5, 2006, at 9:06:05
In reply to Re: one thing Prozac does, not chemical imbalance » Larry Hoover, posted by Caedmon on June 3, 2006, at 13:04:57
> Lar,
>
> I quite agree with your assessment.
>
> - ChrisThank you for saying so. It is in my junk science drawer, but others may place it elsewhere, of course.
Best,
Lar
This is the end of the thread.
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