Psycho-Babble Medication Thread 14806

Shown: posts 1 to 9 of 9. This is the beginning of the thread.

 

VERY interesting theory on AD time lag...

Posted by Bruce on November 8, 1999, at 12:30:02

Article from New Scientist magazine:

PROZAC stimulates the birth of new brain cells in rats, say scientists from New Jersey. The finding gives clues to what causes depression in people, how drugs like Prozac relieve it and why the effect takes so long to kick in.

Just over a year ago, researchers showed that people grow new neurons all the time. This overturned a long-held belief that brain cells, unlike cells in other parts of the body, are not replaced when they die.

Barry Jacobs and Casimir Fornal at Princeton University put together findings from several different brain studies. They knew, for instance, that depressed people have a smaller hippocampus--a structure that is involved in learning and memory--than healthy people.

They also knew that chronic stress can slow neuron birth, or neurogenesis, in the brains of rodents. Stress is thought to contribute to depression. "A little light went on in my head," says Jacobs. "It just occurred to me that maybe this is what depression is all about."

Jacobs and Fornal went on to show that activating one type of receptor for the neurotransmitter serotonin in rats' brains increased the birth of neurons. So they decided to see if Prozac, which belongs to a class of drugs known as selective serotonin re-uptake inhibitors (SSRIs), would have the same effect. SSRIs prevent serotonin from being mopped up, leaving more of it around to transmit messages.

The team gave daily injections of Prozac to five rats for 21 days. Five control rats were injected with saline. During the final 7 days, they also gave the rats a chemical called BrdU, which labels new neurons. When they examined the rats' brains, 69 per cent more new neurons had appeared in the brains of the Prozac-treated rats compared with the controls.

Jacobs and Fornal believe that the waxing and waning of neurogenesis in the hippocampus may be an important factor in explaining why people slump into depression and why they recover with SSRIs. It may also explain why Prozac takes several weeks to improve mood. "The time needed for these newly generated cells to mature and make appropriate connections provides an explanation for the 'therapeutic lag' in antidepressant therapy," Jacobs told the meeting.

Jacobs thinks serotonin could also help to treat other neurological diseases, such as Alzheimer's. But he cautions that it probably won't be of use to healthy people: "Their level of neurogenesis might already be optimal."

 

Re: VERY interesting theory on AD time lag...

Posted by Adam on November 8, 1999, at 17:36:01

In reply to VERY interesting theory on AD time lag..., posted by Bruce on November 8, 1999, at 12:30:02

I've read with great interest about the very exciting discovery of neuronal stem cells,
and the therapeutic implications of adult neurogenesis. From what I understand, however,
the rate of neurogenesis in the adult brain is very small (so small in fact that for years
many experts have dismissed it as a possibility, and it's only with sensitive DNA labelling
and exhaustive histological examination that you can detect it.) Driving up the rate of
neurogenesis by less than a factor of two, while certainly remarkable in itself, doesn't
seem to me to be nearly as profound, potent, or extensive as other biochemical changes caused
by Prozac. How did the investigators make this leap when so many other plausible theories
exist?

Perhaps this is too simplistic, but if one were to realise improvement in mood from increased
neurogenesis in the hippocampus, wouldn't one's memory improve also? And since decreased
neurogenesis in the hippocampus (and other parts of the brain) is a normal function of aging
in the depressed and euthymic alike, why wouldn't giving boosting serotonin in the "healthy"
be a good idea? It would preserve a youthful state in the brain, seemingly.

I get their logic, sometimes. The association with Prozac-induced neurogenesis (and lets not
forget this could be bad for anybody) and antidepressant effect (or its latency, for
that matter) is really pretty thin, if you asked me. I wouldn't go around saying the things
these guys are saying. I'd say it was an interesting result, but I wouldn't even begin to
speculate on benefits or potential harmful effects. Clearly these guys are looking for more
funding from Lily, and I don't applaud their cynicism. But kudos for the intuitive leap that
lead to this discovery.


> Article from New Scientist magazine:
>
>
>
> PROZAC stimulates the birth of new brain cells in rats, say scientists from New Jersey. The finding gives clues to what causes depression in people, how drugs like Prozac relieve it and why the effect takes so long to kick in.
>
> Just over a year ago, researchers showed that people grow new neurons all the time. This overturned a long-held belief that brain cells, unlike cells in other parts of the body, are not replaced when they die.
>
> Barry Jacobs and Casimir Fornal at Princeton University put together findings from several different brain studies. They knew, for instance, that depressed people have a smaller hippocampus--a structure that is involved in learning and memory--than healthy people.
>
> They also knew that chronic stress can slow neuron birth, or neurogenesis, in the brains of rodents. Stress is thought to contribute to depression. "A little light went on in my head," says Jacobs. "It just occurred to me that maybe this is what depression is all about."
>
> Jacobs and Fornal went on to show that activating one type of receptor for the neurotransmitter serotonin in rats' brains increased the birth of neurons. So they decided to see if Prozac, which belongs to a class of drugs known as selective serotonin re-uptake inhibitors (SSRIs), would have the same effect. SSRIs prevent serotonin from being mopped up, leaving more of it around to transmit messages.
>
> The team gave daily injections of Prozac to five rats for 21 days. Five control rats were injected with saline. During the final 7 days, they also gave the rats a chemical called BrdU, which labels new neurons. When they examined the rats' brains, 69 per cent more new neurons had appeared in the brains of the Prozac-treated rats compared with the controls.
>
> Jacobs and Fornal believe that the waxing and waning of neurogenesis in the hippocampus may be an important factor in explaining why people slump into depression and why they recover with SSRIs. It may also explain why Prozac takes several weeks to improve mood. "The time needed for these newly generated cells to mature and make appropriate connections provides an explanation for the 'therapeutic lag' in antidepressant therapy," Jacobs told the meeting.
>
> Jacobs thinks serotonin could also help to treat other neurological diseases, such as Alzheimer's. But he cautions that it probably won't be of use to healthy people: "Their level of neurogenesis might already be optimal."

 

Re: VERY interesting theory on AD time lag..

Posted by Adam on November 8, 1999, at 23:53:47

In reply to Re: VERY interesting theory on AD time lag..., posted by Adam on November 8, 1999, at 17:36:01

> Clearly these guys are looking for more funding from Lily, and I don't applaud their cynicism. But kudos for the intuitive leap that
> lead to this discovery.

OK, I've started mini-flame wars saying things like this before, so please let me apologize right now: My
skepticism about this report I think is warranted, but I have no buisness calling the investigators cynics
because I think their enthusiasm is unfounded. Sorry.

Having said that, I do think it's just plain weird that they would attribute antidepressant action to increased
neurogenesis, given what is known about such phenomena, which is not a whole lot. The paper showing definitively
that neuronal stem cells do in fact exist only came out a short time ago. I don't think this new and very exciting
discovery is all that well understood yet.

And anyway, it doesn't take a genius to see there are some serious holes in this theory. One real problem it
took about ten minutes for me to figure out (and I'm sure these guys thought of this) is why, if Prozac makes you
grow new nerves cells, do the antidepressant effects go away so quickly once you stop taking the drug? They
hypothesize that congenital defects and/or stress lead to a smaller hypothalmus, and this is an underlying cause
of depression. Fine. Without even arguing that point, if in six weeks or however long it takes for the latent
period of antidepressant action to end you have grown back whatever neurons you need to feel better, then why
should you keep having to take the drug? To prevent further damage? Are they suggesting depression is a neuro-
degenerative disease like Parkinsons? Neurodegenerative diseases can lead to depression, but it does not follow that
that is the etiology of all depression, or even a significant fraction of depressive illnesses. Are they suggesting
that neurogenesis in depressed people occurs at a slower rate than healthy individuals? I don't think anyone has
demonstrated that. No one has had time to.

Maybe there's something I'm missing here, but I don't think so. This is too much of a leap too soon for my tastes,
and I have a hard time understanding how these investigators came so confidently to their conclusions.

 

Hmmm: my two cents worth

Posted by Sean on November 9, 1999, at 12:25:26

In reply to VERY interesting theory on AD time lag..., posted by Bruce on November 8, 1999, at 12:30:02

> Article from New Scientist magazine:
>
>
>
> PROZAC stimulates the birth of new brain cells in rats, say scientists from New Jersey. The finding gives clues to what causes depression in people, how drugs like Prozac relieve it and why the effect takes so long to kick in.
>
> Just over a year ago, researchers showed that people grow new neurons all the time. This overturned a long-held belief that brain cells, unlike cells in other parts of the body, are not replaced when they die.
>
> Barry Jacobs and Casimir Fornal at Princeton University put together findings from several different brain studies. They knew, for instance, that depressed people have a smaller hippocampus--a structure that is involved in learning and memory--than healthy people.
>
> They also knew that chronic stress can slow neuron birth, or neurogenesis, in the brains of rodents. Stress is thought to contribute to depression. "A little light went on in my head," says Jacobs. "It just occurred to me that maybe this is what depression is all about."
>
> Jacobs and Fornal went on to show that activating one type of receptor for the neurotransmitter serotonin in rats' brains increased the birth of neurons. So they decided to see if Prozac, which belongs to a class of drugs known as selective serotonin re-uptake inhibitors (SSRIs), would have the same effect. SSRIs prevent serotonin from being mopped up, leaving more of it around to transmit messages.
>
> The team gave daily injections of Prozac to five rats for 21 days. Five control rats were injected with saline. During the final 7 days, they also gave the rats a chemical called BrdU, which labels new neurons. When they examined the rats' brains, 69 per cent more new neurons had appeared in the brains of the Prozac-treated rats compared with the controls.
>
> Jacobs and Fornal believe that the waxing and waning of neurogenesis in the hippocampus may be an important factor in explaining why people slump into depression and why they recover with SSRIs. It may also explain why Prozac takes several weeks to improve mood. "The time needed for these newly generated cells to mature and make appropriate connections provides an explanation for the 'therapeutic lag' in antidepressant therapy," Jacobs told the meeting.
>
> Jacobs thinks serotonin could also help to treat other neurological diseases, such as Alzheimer's. But he cautions that it probably won't be of use to healthy people: "Their level of neurogenesis might already be optimal."


Well, I just don't know one way or the other on
this one. It might be the case that the newly
grown cells are specific to certain neurotransmitter
substrates and do significantly increase the levels
of one or more neurotransmitters/peptides by virute
of increased turnover of gene products in those
areas of the brain. In other words, these are not
dendrites or glial cells they are talking about
but much finer structures along the lines of
axonal and/or re-uptake projections in fairly
localized regions.

But hey, I'm talking out my ass...

 

Re: Hmmm: my two cents worth

Posted by Adam on November 10, 1999, at 0:26:56

In reply to Hmmm: my two cents worth, posted by Sean on November 9, 1999, at 12:25:26

>
> But hey, I'm talking out my ass...
>
I guess that never stopped me :).

I've been thinking more about the implications of increased neural stem cell proliferation
rates, and the implications could be disturbing.

Since we're all speculating wildly (as the investigators mentioned above clearly are) here's
another thing I thought of...

Stem cells exist all over the body. The paradigm is the hematopoietic stem cell that exists in
the bone marrow, and neural stem cells from adult tissues have been grown in culture since the
mid-90s. The first real evidence of a specific stem cell type doing its job in situ was reported
in the journal Cell last January. They showed that ependymal cells (cells that line the
ventricals) could divide and give rise to both neurons and glial cells (specifially astrocytes).
These cells can migrate in response to signals both known and unknown and find their way to where
they are needed (to form scar tissue in a spinal cord injury, for example, or replenish neurons
in the olfactory bulb).

All stem cells have the quality of being "multipotent": they divide and give rise to two new cells.
One is another stem cell like itself, and the other is a cell that will terminally differentiate
into a specific cell type. By "terminally differentiated" I mean that even if the cell can divide
further, it will give rise only to cells just like itself. Neurons are "quiescent"; as far as we
know, they don't divide at all.

Stem cells keep dividing as long as they last. Now, all somatic cells (non-germ cells), including
stem cells, can only divide so many times. All chromosomes in cells contain repetitive, GC-rich
sequences of DNA stuck on on the ends of the molecule called telomeres. Telomeres are synthesised
normally in somatic cells only during embryogenesis. Then enzyme that synthesizes them (telomerase)
isn't active in somatic cells beyond this point. The telomeres function to keep the chromosome
intact-they provide a sort of glue at the end that prevents it from unravelling and undergoing
catastrophic rearrangements. The trouble is, every time a cell divides, it loses a bit of the telomere.
Eventually, the telomere reaches a certain length, which is sensed by the cell. When the cell
reaches this point, it commits suicide. This is an evolutionary consequence of aging. Every cell
has this built-in clock, and it leads to death unless telomerase is active (only in germ cells and
cancerous cells, which are immortal).

If my understanding of neural stem cells is correct, they divide when needed to give rise to cells
that go where they're needed (just like hematopoietic stem cells). It could very well be that the
aging brain starts to decay because our complement of stem cells decreases (as it does in all tissues)
as time passes and cells reach the end of their life span. This will happen sooner or later depending
in part on how many times the cell has divided at a given time. If this rate of division is sped up,
what could this mean? One possibility (and a scary one at that) is that, like the candle burning
twice as bright half as long, you run out of neural stem cells earlier than you would have otherwise.
While it's true you may have a few more neurons than the average person when you reach that point,
if you have fewer stem cells later in life, you might not get the new growth that you need when and
where you need it. If what these guys are saying about Prozac is true, I see this as a distincly
possible scenerio, at least as possible as their functional association with antidepressant effect.
It also could be true of any drug that boosts serotonin levels, if serotonin is in some way the trigger
of a growth signal. This signal could just be mimicking stress (such as injury), and that's why these
cells are dividing 60-some-odd% more.

Kind of creepy, if you ask me.

 

Re: Hmmm: my two cents worth

Posted by Sean on November 10, 1999, at 11:46:08

In reply to Re: Hmmm: my two cents worth, posted by Adam on November 10, 1999, at 0:26:56

>
>
> >
> > But hey, I'm talking out my ass...
> >
> I guess that never stopped me :).
>
> I've been thinking more about the implications of increased neural stem cell proliferation
> rates, and the implications could be disturbing.
>
> Since we're all speculating wildly (as the investigators mentioned above clearly are) here's
> another thing I thought of...
>
> Stem cells exist all over the body. The paradigm is the hematopoietic stem cell that exists in
> the bone marrow, and neural stem cells from adult tissues have been grown in culture since the
> mid-90s. The first real evidence of a specific stem cell type doing its job in situ was reported
> in the journal Cell last January. They showed that ependymal cells (cells that line the
> ventricals) could divide and give rise to both neurons and glial cells (specifially astrocytes).
> These cells can migrate in response to signals both known and unknown and find their way to where
> they are needed (to form scar tissue in a spinal cord injury, for example, or replenish neurons
> in the olfactory bulb).
>
> All stem cells have the quality of being "multipotent": they divide and give rise to two new cells.
> One is another stem cell like itself, and the other is a cell that will terminally differentiate
> into a specific cell type. By "terminally differentiated" I mean that even if the cell can divide
> further, it will give rise only to cells just like itself. Neurons are "quiescent"; as far as we
> know, they don't divide at all.
>
> Stem cells keep dividing as long as they last. Now, all somatic cells (non-germ cells), including
> stem cells, can only divide so many times. All chromosomes in cells contain repetitive, GC-rich
> sequences of DNA stuck on on the ends of the molecule called telomeres. Telomeres are synthesised
> normally in somatic cells only during embryogenesis. Then enzyme that synthesizes them (telomerase)
> isn't active in somatic cells beyond this point. The telomeres function to keep the chromosome
> intact-they provide a sort of glue at the end that prevents it from unravelling and undergoing
> catastrophic rearrangements. The trouble is, every time a cell divides, it loses a bit of the telomere.
> Eventually, the telomere reaches a certain length, which is sensed by the cell. When the cell
> reaches this point, it commits suicide. This is an evolutionary consequence of aging. Every cell
> has this built-in clock, and it leads to death unless telomerase is active (only in germ cells and
> cancerous cells, which are immortal).
>
> If my understanding of neural stem cells is correct, they divide when needed to give rise to cells
> that go where they're needed (just like hematopoietic stem cells). It could very well be that the
> aging brain starts to decay because our complement of stem cells decreases (as it does in all tissues)
> as time passes and cells reach the end of their life span. This will happen sooner or later depending
> in part on how many times the cell has divided at a given time. If this rate of division is sped up,
> what could this mean? One possibility (and a scary one at that) is that, like the candle burning
> twice as bright half as long, you run out of neural stem cells earlier than you would have otherwise.
> While it's true you may have a few more neurons than the average person when you reach that point,
> if you have fewer stem cells later in life, you might not get the new growth that you need when and
> where you need it. If what these guys are saying about Prozac is true, I see this as a distincly
> possible scenerio, at least as possible as their functional association with antidepressant effect.
> It also could be true of any drug that boosts serotonin levels, if serotonin is in some way the trigger
> of a growth signal. This signal could just be mimicking stress (such as injury), and that's why these
> cells are dividing 60-some-odd% more.
>
> Kind of creepy, if you ask me.

I think you're right about the telomerase thing.
Basically it's the Hayflick limit being reached
prematurely right?

It is spooky, but not as spooky as killing
yourself...

 

Re: VERY interesting theory on AD time lag..

Posted by Bruce on November 10, 1999, at 12:41:04

In reply to Re: VERY interesting theory on AD time lag.., posted by Adam on November 8, 1999, at 23:53:47


> Having said that, I do think it's just plain weird that they would attribute antidepressant action to increased
> neurogenesis, given what is known about such phenomena, which is not a whole lot. The paper showing definitively
> that neuronal stem cells do in fact exist only came out a short time ago. I don't think this new and very exciting
> discovery is all that well understood yet.
>
> And anyway, it doesn't take a genius to see there are some serious holes in this theory. One real problem it
> took about ten minutes for me to figure out (and I'm sure these guys thought of this) is why, if Prozac makes you
> grow new nerves cells, do the antidepressant effects go away so quickly once you stop taking the drug? They
> hypothesize that congenital defects and/or stress lead to a smaller hypothalmus, and this is an underlying cause
> of depression. Fine. Without even arguing that point, if in six weeks or however long it takes for the latent
> period of antidepressant action to end you have grown back whatever neurons you need to feel better, then why
> should you keep having to take the drug? To prevent further damage? Are they suggesting depression is a neuro-
> degenerative disease like Parkinsons? Neurodegenerative diseases can lead to depression, but it does not follow that
> that is the etiology of all depression, or even a significant fraction of depressive illnesses. Are they suggesting
> that neurogenesis in depressed people occurs at a slower rate than healthy individuals? I don't think anyone has
> demonstrated that. No one has had time to.
>
> Maybe there's something I'm missing here, but I don't think so. This is too much of a leap too soon for my tastes,
> and I have a hard time understanding how these investigators came so confidently to their conclusions.

I think the researcher's answer would be that, Yes, the new hippocampus cells generally would go away once you stop taking antidepressants. The same forces that helped produced the depression in the first place (cortisol-induced hippocampus shrinkage) would quickly reassert themselves and begin anew at eating away the hippocampus.

Many people need chronic AD treatment. A few months of treatment provides relief for a few months, but a relapse is highly likely once one serious depression has occurred.

You raise some good points. One question that occurred to me was, would another AD type also induce neogenesis? If it is just serotonin, how would this model explain the feact that people get better on norepinehrine or dopamine based drugs? Also, this model doesn't explain why only ~70% of people taking an SSRI get better. Presumably the extra serotonin would spur hippocampus growth even in the non-responders, yet they do not respond...

At any rate, it's a fledgling theory, and seems worthy of further attention. It cannot yet answer all questions put to it. You are probably right, in that there are many paths leading to the same outcome - depression.

Bruce

 

Another interestng theory on cause of depression &

Posted by dj on November 10, 1999, at 16:19:51

In reply to Re: VERY interesting theory on AD time lag.., posted by Bruce on November 10, 1999, at 12:41:04

October 26, 1999 -- NYTimes

New Way of Looking at Diseases of the Brain

By SANDRA BLAKESLEE

A highly respected neuroscientist has developed a provocative new theory of how the brain is organized which, if confirmed, would explain how and why the mind produces symptoms found in several seemingly unrelated disorders.

According to the theory, the deep sadness in severe depression, the hand wringing in obsessive compulsive disorder, the ringing in the ears of tinnitus, the unrelenting discomfort of chronic pain and the shaking and immobility seen Parkinson's disease all stem from the same basic brain defect: a decoupling of two brain regions that normally fire their cells in synchrony.

If the theory is correct, it would explain why experimental surgical techniques involving implanting electrodes in the brain to treat Parkinson's disease and depression seem to work so well, and it would expand their application to other brain diseases.

The neuroscientist, Dr. Rodolfo Llinas, a professor at New York University Medical School, presented his findings on Sunday night in Miami to some 4,000 researchers attending the annual Society for Neuroscience meeting.

Although the theory has not yet been subjected to peer review, a paper describing the work was submitted last week to Proceedings of the National Academy of Sciences and accepted for publication in just two days.

Dr. Llinas is a member of the academy, which often publishes the work of leading scientists or their protégés when the ideas are new and have not yet been tested by others.

"This work is very important," said Dr. Edward Jones, president of the Society for Neuroscience and director of the Center for Neuroscience at the University of California in Davis.

"What makes it so compelling is that it doesn't come completely out of left field.

It builds on a body of work that's been growing for some time.

Everyone will say wow, yes!"

Because these new insights into brain organization, if confirmed, would almost certainly promote the use of surgery to treat psychiatric and neurological diseases, other scientists urged caution in applying the theory. They are concerned because psychosurgeries that were tried 30 to 40 years ago in these same regions of the brain made many people mentally incompetent.

The theory involves two brain areas -- the cerebral cortex and the thalamus -- and how they communicate.

The cortex is a thickly folded band of tissue that carries out higher mental capacities in humans and other mammals. It is composed of six layers of cells that are highly interconnected and organized into specialized regions that allow people to move their bodies, plan for the future, talk, listen, sense touch, respond to emotions and carry out other functions. The sixth layer of these cells is also directly connected through nerve fibers to cells in the thalamus, an older brain structure that is just under the cortex.

The thalamus is usually thought of as a relay station. Virtually all information flowing from the outside world and lower brain regions must go through the thalamus before being passed on to the cortex.

But according to Dr. Llinas, the thalamus does much more than simply pass information.

The way that it coordinates its activity with the cortex, he says, gives rise not only to the symptoms seen in many neurological and psychiatric diseases, but to consciousness itself.

It does so through what Dr. Llinas calls thalamo-cortical oscillations. The thalamus contains special cells that pass tiny electrical currents across their membranes in a highly coordinated manner, Dr. Llinas said in a telephone interview. Rather than firing sporadically and singly, like other nerve cells, the cells in the thalamus oscillate, firing in groups together at various frequencies.

By virtue of their connections, these thalamic cells then cause cells in layer six -- the layer of the cortex closest to them -- to oscillate at the same frequency. This coordination between these oscillating cells in the cortex and thalamus, which are constantly flipping signals back and forth, binds information from different regions of the brain into complete actions, perceptions, movements and into consciousness itself, he said.

When the cells oscillate at a high frequency, the brain is awake and alert.

When they fall into low frequencies, the brain becomes disconnected, unconscious and falls asleep.

In studying patients with various brain diseases, Dr. Llinas and his colleagues noticed that particular regions of their thalamuses oscillated at abnormally low frequencies, as if those regions were asleep.

When this happens, Dr. Llinas said, key parts of the cortex are decoupled from the thalamus. Those parts of the cortex then become overly excited because they are no longer under proper control, he said, and symptoms of dysfunction emerge.

For example, a defect in one tiny part of the thalamus that projects to one of the higher areas controlling movements can cause those movements to become uncoordinated.

The result is the tremors seen in Parkinson's disease.

If the defect is a fraction of an inch away, a different part of the region controlling movement is affected, resulting in the rigidity seen in many patients.

Chronic-pain sufferers also have sluggish regions of the thalamus, Dr. Llinas said.

Areas of the cortex that deal with pain become overexcited, producing intense discomfort that does not respond to drugs.

Dr. Llinas speculates that the same underlying defect causes some types of depression, most tinnitus and obsessive compulsive disease. In each case, according to his theory, a part of the thalamus is out of phase with the cortex which, unregulated, produces symptoms of profound sadness, ringing in the ears or endless hand washing.

All these disorders might be treated by implanting electrodes into the thalamus to break the abnormal oscillation patterns, Dr. Llinas said. In fact, the most effective treatment for Parkinson's patients who do not respond to drug therapy involves putting electrodes directly into the thalamus. "This breaks the abnormal disconnection and the person immediately gets better," Dr. Llinas said. "But you have to keep the electrode in. It's like a pacemaker." Similar surgeries have been tried successfully for chronic pain and depression. In each case, the electrode is targeted on only a few thousand cells.

 

Re: VERY interesting theory on AD time lag..

Posted by Adam on November 10, 1999, at 16:40:58

In reply to Re: VERY interesting theory on AD time lag.., posted by Bruce on November 10, 1999, at 12:41:04

Perhaps. My understanding of their theory is that stress (which induces production of the stress hormone cortisol) leads to damage, which leads to depression. If the stress is removed (say, a childhood trauma)
and the depression is releived, why should this process continue? And again, why should relapse occur so quickly?

As for their proposition to use SSRIs as a treatment for Alzheimers, I recently attended a conference (mostly on gene therapy, though tissue grafting in that context was discussed). There are lots of people who
are looking to use neural progenitor cells from a variety of possible sources for just such a purpose, as well as other neurodegenerative diseases. It struck me that this approach (as a remedy) might save the patient
but not the person. If the formation of amyloid plaques isn't stopped, then older cells (which, one assumes, are the storage sites of old memories) will keep dying. Even if new cells could be coaxed into the
places where necrosis is occurring (a big if), they won't save what is lost, just replace it with something new. The brain normally has limited plasticity, and some theorize this allows us to retain long-term memory.
I could imagine a patient who, with constant reinforcement, might remember that their spouse is their spouse, but has long forgotten their wedding day, or why they fell in love in the first place. If there is
anything merciful about Alzheimer's, (my grandfather died of it), it's that the sufferer becomes so demented that they are no longer cognizant. To preserve awareness without curing the underlying disorder could be
as much a curse as anything else that might happen. It would at best only be a partial solution.

>
> I think the researcher's answer would be that, Yes, the new hippocampus cells generally would go away once you stop taking antidepressants. The same forces that helped produced the depression in the first place (cortisol-induced hippocampus shrinkage) would quickly reassert themselves and begin anew at eating away the hippocampus.
>
> Many people need chronic AD treatment. A few months of treatment provides relief for a few months, but a relapse is highly likely once one serious depression has occurred.
>
> You raise some good points. One question that occurred to me was, would another AD type also induce neogenesis? If it is just serotonin, how would this model explain the feact that people get better on norepinehrine or dopamine based drugs? Also, this model doesn't explain why only ~70% of people taking an SSRI get better. Presumably the extra serotonin would spur hippocampus growth even in the non-responders, yet they do not respond...
>
> At any rate, it's a fledgling theory, and seems worthy of further attention. It cannot yet answer all questions put to it. You are probably right, in that there are many paths leading to the same outcome - depression.
>
> Bruce


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