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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 18 of 18. This is the beginning of the thread.
Posted by SLS on September 10, 2005, at 8:07:34
September 8, 2005
CONTACT: Karen Kreeger
(215) 349-5658
karen.kreeger@uphs.upenn.edu
Penn Awarded $1.8 Million to Search for New Mood-Disorder Drugs,
in a Collaboration With Wyeth Research Laboratories(Philadelphia, PA) - The National Institutes of Mental Health (NIMH) has awarded the University of Pennsylvania School of Medicine $1.8 million over the next three years to establish a National Cooperative Drug Discovery Group for the Treatment of Mood Disorders (NCDDG-MD). This group is comprised of researchers from the Center for Neurobiology at Penn and the Neuroscience Discovery Department at Wyeth Research Laboratories, Princeton N.J. The aim of this National Institutes of Health (NIH)-sponsored academic-industry collaboration is to develop new antidepressant drug treatments based on the role of neurogenesis (the production of new neurons) in regulating stress and depression.
“The NIH wants drug-development programs to jump-start new approaches for creating drugs to treat depression,” explains Irwin Lucki, PhD, Professor of Psychiatry and principal investigator of the Penn component of NCDDG-MD.
The Wyeth component is led by Lee Schechter, PhD, who is the Therapeutic Area Head for Depression and Anxiety Research in Neuroscience Discovery. “The previous research findings demonstrating that antidepressants can induce neurogenesis in the brain has opened up a new and exciting area for scientific investigation delving into novel mechanisms of antidepressant drug action,” says Schechter. “We are very excited about this initiative with Penn under the NCDDG-MD program.”
According to the World Health Organization (WHO), approximately 121 million people currently suffer from depression, which can lead to reduced productivity in the workplace and home. “Depression causes immense financial burdens for individuals and their families, as well as society,” echoes Lucki. WHO estimates that the annual costs of mental illness in the U.S. is close to $148 billion. Although effective treatments for depression do exist, they are marked by limitations, such as side effects and a three-to-five-week delay before they take effect. And, less than 60 percent of patients seeking treatment respond to current antidepressants.
In recent years, advances in imaging techniques have allowed researchers to scan the brains of patients suffering from depression. Such brain images show distinct shrinkage in the hippocampus and cortex, regions known to play a role in mediating mood and cognitive reasoning. Animal studies reveal that chronic stress leads to similar volume and cell loss in these brain regions, suggesting a link between depression and stress throughout the lifetime.
“Increasingly, we are learning that certain areas of the brain are responsible for generating new cells, and this renewal process is causing us to reexamine the way that stress affects the brain,” explains Lucki. Stress reduces the amount of neurogenesis, or cell growth, in these areas of renewal. Conversely, chronic administration of antidepressant drugs increases neurogenesis. The NCDDG-MD is in the midst of identifying compounds that facilitate neurogenesis in key areas of the brain to develop innovative therapies for depression.
Recently, Penn and Wyeth researchers examined a hormone called insulin-like growth factor (IGF-1) that has been shown to promote neurogenesis. Brian Hoshaw, PhD, research associate in the Department of Psychiatry at Penn, in collaboration with Jessica Malberg, PhD, Senior Research Scientist in Neuroscience Discovery at Wyeth, discovered that IGF-1 produces behavioral effects similar to antidepressant treatments in animal models. With further examination of the way that IGF-1 and other neurotrophins increase neurogenesis, the research team may be able to develop better antidepressant drugs.
The NCDDG-MD is also developing an animal model capable of detecting the effects of antidepressants on chronic stress using neurogenesis. With such a model, researchers could begin to better understand the delay in drug efficacy of antidepressants and how this may relate to changes in neurogenesis, suggest Lucki and Schechter.
Lucki, Hoshaw, and Penn colleagues state no financial interests in Wyeth.
Posted by linkadge on September 10, 2005, at 21:05:47
In reply to NIMH funds research into neurogenesis drugs, posted by SLS on September 10, 2005, at 8:07:34
I wonder what other sorts of things affect IGF-1 ?
Any AD drugs? Excercise ?
Linkadge
Posted by linkadge on September 11, 2005, at 12:28:33
In reply to Re: u sure do remind me of, posted by linkadge on September 11, 2005, at 9:49:56
I have been doing some reading. There seems to be a link between slow wave sleep, HGH release and IGF-1.
If SSRI's decrease slow wave sleep, and reduce HGH secretion, then I can just put 2 and 2 together that they might interfere with IGF production.
Linkadge
Posted by denise1966 on September 12, 2005, at 11:59:05
In reply to NIMH funds research into neurogenesis drugs, posted by SLS on September 10, 2005, at 8:07:34
Hi,
I don't get it
For a start, there are many people (including myself in the past, when
I was lucky) respond to ADs in a matter of days, what's happening there
then, did we sprout new neurons in a matter of days? Please don't put this down to placebo, that only infuriates me, I know for sure it wasn't placebo, I don't get placebos, if that was the case it's a pity I didn't get a placebo response when I had hypnotherapy, rTMS, vitamens, johns wort, Sam E etc etc. So please don't even mention placebo to me.Secondly, why do antidepressants stop working for people, if they
worked because they initiated neurogenis then why would they sudddenly
stop working?I expect people don't know the answers, it just me wondering to myself again.
Because nothing really makes sense.
Denise
Posted by linkadge on September 12, 2005, at 17:47:43
In reply to Re: This neurogenesis theory doesn't ring true., posted by denise1966 on September 12, 2005, at 11:59:05
I consider depression helped in two phases. The first phase is HPA axis regulation. High levels of cortisol supress the natural regulation of neurogenesis.
So, many times when people are depressed, the thing thats going to work the fastest is something that will calm them down. Benzo's have helped my depression when it gets really bad.
Some AD's (and zyprexa) can offer that immediate HPA axis regulation, which can help depression.
After this, you need to look at why the HPA axis got dysregulated. Generally this happens becuse the coping stradegy one is useing is not working very well.
In order to maintain that HPA axis regulation you need to learn new ways to approach your stressors.
Neurogenesis makes the day fresh. It is the part of the brain that says, ok today was crap, but tomorrow I am going to come up with a faster/easier way to deal with things that won't get me P.O.'d and stressed to the brink. That is neurogenesis, when the brain says "I am going to look at my problems from a different angle".
IN order to stay happy we need to believe that the future is going to be different. Without new neurons we get stuck in ruts.
Linkadge
Posted by Pfinstegg on September 12, 2005, at 23:22:09
In reply to Re: This neurogenesis theory doesn't ring true., posted by linkadge on September 12, 2005, at 17:47:43
Most of the agents that help depression do so by 1)activating the left frontal areas, 2)resetting the HPA axis at a lower level, and 3)allowing normal neurogenesis to resume in the hippocampus and probably other areas. One of the results of the neurogenesis, seen when SSRI's are used, is that more serotonin gets produced, and then stays around in the inter-cellular spaces.It seems as though most of the AD's initially do one or more of these things. TMS and ECT do all of them. I should put in the caveat that- not for everyone, and not permanently. I recently noticed an article which said that TMS, at regular intervals. plus the right AD is producing about a 70% remission rate. That's what has worked for me, so I have a bias in favor of it; I was so sorry to learn that it didn't work for you, Denise. And Link, what happened with your TMS machine? Do you think you used it too often?
As to why AD's poop out, I don't think this huge problem has been properly investigated yet. My own feeling- not based on very much hard evidence- is that the SSRIs and SNRIs cause an abnormal situation-too much serotonin in the brain, so that long-term, your dopamine drops, resulting in anhedonia, and the number of neurons producing serotonin drops, too, because the flood of serotonin makes one's brain think that these neurons are not needed. The drugs which seem to work best long-term are the MAOIs, which boost the amounts of serotonin, nor-epinephrine and dopamine about equally. I'm speculating that, with them, things are in better balance, and you don't lose any particular type of neuron. Of course, they're not so easy to take! Maybe the selegiline patch will work out well.
Posted by SLS on September 13, 2005, at 0:10:49
In reply to Neurogenesis, posted by Pfinstegg on September 12, 2005, at 23:22:09
Hi Pfinstegg.
> I recently noticed an article which said that TMS, at regular intervals. plus the right AD is producing about a 70% remission rate. That's what has worked for me, so I have a bias in favor of it;
What was the suggested interval between TMS treatments?
Thanks.
I am not so convinced that neurogenesis is the cause of improvement as it is the result. Not yet, anyway.
I would sure like them to study more closely medication "poop-out" or tachyphylaxis. My responses to antidepressants and mood-stabilizers persist for only three days, usually occurring between 7 and 14 days after initiating treatment. The consistency of this pattern is remarkable. For the moment, I am somewhat focused on presynaptic events to account for this pattern. For those people whose improvement lasts for months or years before relapse occurs, it may be that whole brain circuit systems must be considered, as you described. I would be inclined to look at changes in postsynaptic receptor sensitivities or second messenger / gene transcription systems as the facilitators of these contratherapeutic events.
- Scott
Posted by linkadge on September 13, 2005, at 8:23:09
In reply to Re: Neurogenesis, posted by SLS on September 13, 2005, at 0:10:49
Neurogeneisis need not necessarily be brand new neurons. It can mean the reestablishment of previous connections.
Neurogeneisis happens in all areas of the brain. In the pleasure centres of the brain too.
When you're depressed it may be from broken limbic circutry. When connections are restablished those feelings come back.
Its not the only theory.
But we know that growth factor injections produce similar AD effects (NT-3 NGF, BDNF, GDNF etc)
Did you see that 60minautes episode on parkinsons and GDNF, it was crazy. One guy coudn't move at all, but after 2 years on GDNF he was able to walk over and hope on a tractor to ride.
That is a parralell that I see to mood disorders. Depression is parkinsons of the limbic system, and those growth factors may be the best chance we have to walk again.
Linkadge
Posted by denise1966 on September 13, 2005, at 9:25:09
In reply to Re: Neurogenesis, posted by SLS on September 13, 2005, at 0:10:49
Scott,
Yes I'm definately inclined to agree with you about neurogenesis being the result of the improvement but not the improvement itself. Not that I know jack sh*t :-)
It's very strange that you respond for just brief periods of time and then relapse again, I wonder what's going on there.
The more I read about the research they are doing the more confused I get and scared I get that they might be barking up the wrong tree but I guess their studies into neurogenesis will reveeal other things. I hope they get there in 3 years.
I really wish you and Linkadge would get well soon so that you could both go into this line of work, I'm sure with both of your experiences with depression, interest and intelligence you'd get things moving a lot faster.
Denise
Posted by denise1966 on September 13, 2005, at 9:30:02
In reply to Re: This neurogenesis theory doesn't ring true., posted by linkadge on September 12, 2005, at 17:47:43
Linkadge,
I would have thought if I had high levels of cortisol it would show up somehow in physical symptoms and also my I did suppress to dexamethasone so wouldn't this mean that I don't have a problem with my HPA Axis?
Do you think that this GDNF would help depressives too?
I forgot to ask you before but have you ever tried taking 10mg of Zyprexa now and again rather than a benzo or small dose Zyprexa?
Denise
Posted by SLS on September 13, 2005, at 10:21:50
In reply to Re: Neurogenesis, posted by linkadge on September 13, 2005, at 8:23:09
Hi Linkadge.
Thanks for the insights.
Your observations and comments are compelling. I really hope that growth factors might represent a potent therapy for depression, even if it only works in conjuction with standard antidepressants.
- Scott> Neurogeneisis need not necessarily be brand new neurons. It can mean the reestablishment of previous connections.
>
> Neurogeneisis happens in all areas of the brain. In the pleasure centres of the brain too.
>
> When you're depressed it may be from broken limbic circutry. When connections are restablished those feelings come back.
>
> Its not the only theory.
>
> But we know that growth factor injections produce similar AD effects (NT-3 NGF, BDNF, GDNF etc)
>
> Did you see that 60minautes episode on parkinsons and GDNF, it was crazy. One guy coudn't move at all, but after 2 years on GDNF he was able to walk over and hope on a tractor to ride.
>
> That is a parralell that I see to mood disorders. Depression is parkinsons of the limbic system, and those growth factors may be the best chance we have to walk again.
>
>
> Linkadge
>
>
>
>
>
Posted by Pfinstegg on September 13, 2005, at 11:17:26
In reply to Re: Neurogenesis, posted by SLS on September 13, 2005, at 0:10:49
As a non-approved treatment, doctors and patients are still trying to figure out together what works best for each person. Dr. Hutto (Atlanta) says he has one man who comes every six months for ONE treatment, and at the other end of the range, a woman who comes every three weeks for four treatments. Both also take ADs and are doing well. I go every two months for four.treatments. Dr. George at So. Carolina recently published a paper about maintaining bipolar patients in remission with one treatment per week for a year, in addition to medication, which had not worked well by itself.
Posted by linkadge on September 13, 2005, at 13:18:35
In reply to To Linkadge, posted by denise1966 on September 13, 2005, at 9:30:02
I've tried taking zyprexa, but I don't really have the same reaction as you do.
I can calm me down when I feel kind of overstressed, but it is not my ideal chill pill.
Linkadge
Posted by linkadge on September 13, 2005, at 13:47:15
In reply to Re: Neurogenesis » linkadge, posted by SLS on September 13, 2005, at 10:21:50
The thing is that you can mess around with the neurotransmitters and HPA axis, but it has been shown in tests that if you block the neurotrophic effects of the meds, you block the behavioral effects of the meds. Especially in cases of risk avoidance, and stress induced behavioral helplessness.
Infact, it can be shown that clinically more effective AD's have more effect on growth factors, than do drugs will fewer neurotrophic effects.
With ECT being the formost in its induction of BDNF and clinical effect.
Linkadge
Posted by linkadge on September 13, 2005, at 16:09:30
In reply to Re: Neurogenesis, posted by linkadge on September 13, 2005, at 13:47:15
I've said it before, but I think that they should really look into the neurotrophic effects of the anthocyannin dyes found in blueberries.
They are finding that they are robustly neurotrophic. They also release dopamine in a dose dependant manner.
Linkage
Posted by deniseuk190466 on February 7, 2007, at 13:41:32
In reply to NIMH funds research into neurogenesis drugs, posted by SLS on September 10, 2005, at 8:07:34
Hi,
Does anyone know if anything is happening with this?
Denise
Posted by FredPotter on February 7, 2007, at 14:03:47
In reply to Re: Neurogenesis, posted by SLS on September 13, 2005, at 0:10:49
When I looked up neurogenesis on the net I got loads of hits about work into inducing it but that no-one has succeeded yet but that it's feasible. The peripheral nervous system yes, but not the CNS yet. So what's the story? Are we talking of dendritic growth, axon growth or completely new neurons? Are they referring to new neurons in the spinal cord rather than the brain?
Fred
Posted by deniseuk190466 on February 8, 2007, at 14:15:25
In reply to Re: Neurogenesis, posted by FredPotter on February 7, 2007, at 14:03:47
Hi Fred,
Well I'm not sure but I was sort of hoping that they might have made some progress some where.
Denise
This is the end of the thread.
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