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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 13 of 13. This is the beginning of the thread.
Posted by Squiggles on August 7, 2005, at 12:11:59
I've come across this theory that lithium
has neurogenerative and neuroprotective
properties in the brain (cells and neurons?).
There is some optimism that lithium can
therefore be used not only for bipolar illness,
but such degenerative brain diseases as
Alzheimer's, Parkinson's and others.An example of research in this are is
Dr. Husseini Manji's work (Chief of the Laboratory of Molecular Pathophysiology at the National Institute of Mental Health), seehttp://www.bpkids.org/site/
PageServer?pagename=lrn_004DrI have a question about this theory: if
lithium protects, even regrows neurons or
brain cells, and thus protects the brain
from derpession and bipolar depression,
how is it that upon cessation of the drug,
bipolar symptoms return? Does it have
something to do with the rate of neural
growth? As i have written here before,
I experienced severe and sucididal psychotic
bipolar symptoms after 5 months on a corrupt
or depleted or low dose of lithium preparation
and was revived on reistatement of my old strong
preparation.Any suggestions would be appreciated.
Thank you
Squiggles
Posted by linkadge on August 7, 2005, at 16:58:13
In reply to Neurogenerative properties of lithium, posted by Squiggles on August 7, 2005, at 12:11:59
I would think that the neurorestorative properties of lithium are just some of the properties. It also stabalizes glutamate neurotransmission which is probably neuroprotective.
It is my understanding that the disease causes the atrophy, not the other way around. Meaning that when the drug is stopped, the disease will start again and the atrophy will probably return.
(the disease will start first then probably the atrophy later)Divalproex has some neuroregenerative properties but not nearly to the same degree as lithium. Carbamazapine has little effect in this regard.
It is funny because most antidepressants show some ability to grow new neurons in the hippocampus. Lithium affects this region, but also affects the frontal cortex (subgenual prefrontal), grey matter etc.
Linkadge
Posted by Squiggles on August 7, 2005, at 17:08:38
In reply to Re: Neurogenerative properties of lithium, posted by linkadge on August 7, 2005, at 16:58:13
What is the difference between the
"disease" and the "atrophy" -- aren't
they the same thing?Squiggles
Posted by linkadge on August 7, 2005, at 19:50:23
In reply to Re: Neurogenerative properties of lithium, posted by Squiggles on August 7, 2005, at 17:08:38
Some researchers believe that bipolar disorder is a genetic disease related to a specific abnormality in glutamate neurotransmission.
We know that carabazapine (tegretol) can treat some people's bipolar without producing trophic capabilities, and/or without producing neurogenesis.
So the disease may start because of a abnormality in the regulation of certain neruomodulators, but may progress and worsen due to the downstream neurodegenerative effects of this disregulation.
Lithium may have a broader theraputic application thant tegretol due to its ability to produce neuromodulation *and* neurogenesis.
Linkadge
Posted by Squiggles on August 7, 2005, at 21:29:52
In reply to Re: Neurogenerative properties of lithium, posted by linkadge on August 7, 2005, at 19:50:23
I appreciate the explanation. I can't
understand much of this, partly because
the medical nomenclature is unfamiliar,
and mostly because this is terra incognita
to me.> Some researchers believe that bipolar disorder is a genetic disease related to a specific abnormality in glutamate neurotransmission.
Yes, I've heard of the glutamate theory, as
well as the lithium ions crossing the cell membrane theory, vaguely;
>
> We know that carabazapine (tegretol) can treat some people's bipolar without producing trophic capabilities, and/or without producing neurogenesis.Maybe tegretol is similar to lithium, without
the neurogenerative side effects?
>
> So the disease may start because of a abnormality in the regulation of certain neruomodulators, but may progress and worsen due to the downstream neurodegenerative effects of this disregulation.
>
Hmm, sounds hypothetical. But i'm a layman.> Lithium may have a broader theraputic application thant tegretol due to its ability to produce neuromodulation *and* neurogenesis.
I guess I just have to study this stuff, to
say anything worthwhile. I do notice however,
that there is great emphasis on the tail-end
of the illness - i.e. the effects on the brain,
and not much on prime causes, like endocrinological changes that may effect the brain. Just a thought, because Kraeplin did
menion many possible causes (with genetic being
the most likely) but also atherosclerosis of the
brain, as well as metabolic changes. Also,
the fact that post-partum depression seems
related to hormonal changes may give one the
impression that endocrinology is not considered
as important as neurology.Squiggles
>
>
> Linkadge
>
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Posted by linkadge on August 8, 2005, at 15:22:37
In reply to Re: Neurogenerative properties of lithium, posted by Squiggles on August 7, 2005, at 21:29:52
"Maybe tegretol is similar to lithium, without
the neurogenerative side effects? "It stabalizes the calium and sodium channels (which would hopefully protect against further dammage) but does not seem to have many trophic capabilities.
It is known that lithium is linked to fewer suicides than either tegretol or depakote.
I would assume that its trophic capabilities have something to do with this.Linkadge
Posted by Squiggles on August 8, 2005, at 16:03:59
In reply to Re: Neurogenerative properties of lithium, posted by linkadge on August 8, 2005, at 15:22:37
> "Maybe tegretol is similar to lithium, without
> the neurogenerative side effects? "
>
> It stabalizes the calium and sodium channels (which would hopefully protect against further dammage) but does not seem to have many trophic capabilities.
>
> It is known that lithium is linked to fewer suicides than either tegretol or depakote.
> I would assume that its trophic capabilities have something to do with this.
>
> Linkadge
>
>
>The neurons or dendrites or whatever that
become more robust or actually grow [?]
in the brain after lithium treatment --
are they specific to emotional stability?
Posted by Squiggles on August 8, 2005, at 16:44:18
In reply to Re: Neurogenerative properties of lithium, posted by linkadge on August 8, 2005, at 15:22:37
Here is one good Google hit i got on
neurotrophic lithium
Notice the meaning of neurotrophic - i.e.
much like a fertilizer or growth accelerator
of neurons;biopsychiatry.com/neurotrophic-moodstabilisers.htm
[insert http://www. prior to line]The foundation of this theory seems to rest
on postmortem brain findings of cell atrophy
and loss in depressives and manic-depressives.
This is correlated by MRI studies, i.e. "CNS
volume reduction" [gives a really new twist
to the phrase head-shrinker :-)];Chronic lithium uses does two things accoding
to this article:1. has neuroprotective effects in preclinical
paradigms [i am not sure what this means],and
2. enhances hippocampal neurogenesis
[ does this mean that the hippcampus neuronal
activity improves or actually changes in
structure?] N-acetylaspartate is mentioned
as something that is increased by lithium - it
is a marker - is this significant to the observation of the brain or to is function?As for the MRI evidence of gross general
increase in brain matter volume - can we
ask if this is a good thing? Is it necessarily
related to the smaller brain volume seen
in depressives? Or are there other states
or conditions were small brain volume is
idiosyncratic (e.g. women are known to have
smaller brains) or just different individuals.
Furthermore, is there evidence that affective
disorders actually shrink the brain, or could
it be something else, such as disease, or
very high on my list - drugs.And once gain, my pet question if infact
lithium and other mood-stabilizers can
contribute to not only neuroprotection but
neural growth of the brain , that should
make it immune to further depression states.
But as we see when the drug is stopped, the
depression returns. Perhaps i just have a hard
time understanding this.Thanks for reading.
Squiggles
Posted by linkadge on August 8, 2005, at 17:39:51
In reply to Re: Neurogenerative - some questions, posted by Squiggles on August 8, 2005, at 16:44:18
I don't think that overal size matters more than functionality.
When you're depressed, you experience a lack of ability to experience joy. It may be that the joy, or happiness areas of the brain are atrophied.
But its not just that. When you're depressed, you can't remember the good times, you literally can't remember them. Creating new brain cells is probably necessary to keep things new so that you don't get stuck in any one particular negative emotion. Neurorestoration may bring back to life the memories and experiences of the past who define who you are.
I saw a video on the brain done by David Sazuki. Anyhow it showed a picture of a mouse brain cell sample that had undergone a tramatic injury.
On the one side of the screen they showed the group of brain networks trying to reconnect themselves, kind of like a tree branching out, it was very slow.
On the other side of the screen they had a similar sample of cells that had been bathed in a certain growth factor (I think BNDF). This particular group of cells grew, branched out, and reconnected at an astonishingly faster rate than the sample with no growth factor applied.
So it may be that a catastophic neurological event has occured in the limbic system and that these growth factors work to restore its functionality.
Linkadge
Posted by linkadge on August 8, 2005, at 17:43:49
In reply to Re: Neurogenerative - some questions, posted by Squiggles on August 8, 2005, at 16:44:18
Lithium increases overall grey matter volume
see the image at:http://www.med.wayne.edu/neuroscience/labs/bird/pdfs/lancet-356-9237-2000.pdf
It enhances frontal cortex neurogenesis, and hippocampal neurogenesis too.
Linkadge
Posted by Squiggles on August 8, 2005, at 17:53:22
In reply to Re: Neurogenerative - some questions, posted by linkadge on August 8, 2005, at 17:39:51
Interesting. Well, I'm not complaining;
it's hard to make a direct connection
parallel style between emotive and cognitive
states and exactly what is necessary physically
in the brain to evoke these conscious states.
That may be a systemic problem, philosophically
and physically.Certainly, I am aware of the difference between
lithiated and non-lithiated states and it's
very different. Something serious is being
readjusted on lithium -- as if a balance that
has lost its equilibrium swing regains it
with lithium. It's hard to describe.There is no depression (maybe sadness at
sad events) - it's incredible. What I like
about lithium is its "clarity"; possibly
other ADs are like that, but i don't think
so after speaking to people. By "clarity"
I mean that your thinking and mental state
is unfuzzy, like a hyper-pixel picture, clear,
and unperturbed by affective colouring.
That is if you are lucky to keep within
the therapeutic index dose.As for the mice and rats (i saw the seizure
evocation - poor things), i do wish they would
leave the animals alone.Squiggles
Posted by linkadge on August 8, 2005, at 18:19:05
In reply to Re: Neurogenerative - some questions, posted by Squiggles on August 8, 2005, at 17:53:22
I guess that the bottom line is that the findings are pointing to the idea that lithium is promoting a healthier brain, both pysically and emotionally.
This is a good link too.
http://www.nature.com/news/2003/030310/pf/030310-11_pf.html
Posted by Dr. Bob on August 8, 2005, at 22:10:29
In reply to Re: Neurogenerative - some questions, posted by Squiggles on August 8, 2005, at 16:44:18
> biopsychiatry.com/neurotrophic-moodstabilisers.htm
> [insert http://www. prior to line]FYI, you can just post a URL directly, for example:
http://www.biopsychiatry.com/neurotrophic-moodstabilisers.htm
Bob
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