[Medicine-for-people] Depression, Dementia, and Lithium

Thu May 3 11:57:48 PDT 2007

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Medicine for People!

May 2007
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Contents
Depression, Dementia, and Lithium
 - Lithium is an Essential Nutrient
 - Lithium and Bi-Polar Disorder
 - Lithium Increases Gray Matter in People with Bipolar Disorder
 - Lithium Protects the Brain from Dementia
 - Lithium and Depression
 - Lithium and Stroke
 - Adverse Effects of Lithium
 - Summary

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Depression, Dementia, and Lithium
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== Lithium ==
Some time ago one of the children in our practice, a child with a learning
disorder, developed a new and disturbing symptom- trichotillomania.
Trichotillomania is the fancy term for hair-pulling; George had bald areas
on his scalp from playing with bits of hair on his head.

What could we do?

Searching the National Library of Medicine,  I found a report  that lithium
had been effective in eight of ten children with trichotillomania.  We
started George on a low dose of lithium.

Lithium, you ask?  Isn't that for people with bi-polar (manic-depressive)
disorder?

== Lithium is an Essential Nutrient ==
Well, yes, dear Reader, but the beneficial effects of lithium on brain
structure and individual mood are far too powerful to leave it in that
pigeonhole.  We, as individuals and as a society, need to recognize that
lithium is an essential component of our diet and our physiology.
Essential as in "required."  In areas where lithium levels are low or
absent in the drinking water, criminal behavior and drug abuse are higher
than in areas with adequate lithium in the water.  Lithium levels are lower
in the hair of learning disabled students as well as violent criminals.
When researchers gave low-dose supplements of lithium to those same groups,
they discovered more stability of mood.

So lithium has much more value to us as individuals and as a society than
we're commonly aware of.  But since we all know lithum as a treatment for
bipolar disorder, let's start there.

== Lithium and Bi-Polar Disorder ==
While doctors have written about bi-polar disorder since ancient times,
only in 1949 was lithium first described as an effective mood-stabilizing
agent for it, and only in 1970 was lithium approved by the FDA.  I have
many patients who happily take lithium to maintain a normal life despite
bipolar disorder, and many who miss the "ups" when they take lithium and so
avoid it and its alternative, valproic acid (Depakote).

In these recent exciting decades our new technologic tools have allowed us
to see into the living brain.  Scans show that some areas of the brain
shrink by 40 percent in volume in people with untreated bipolar disorder.
Treat those people with lithium, however, and you can prevent this shrinkage.

== Lithium Increases Gray Matter in People with Bipolar Disorder ==
Our brains contain neurons, which do the processing.   Many of our neurons
are in the outer layer, the cortex of the brain. When we look at the brain
as a whole, this outer layer appears gray, hence the expression "gray
matter." Deeper in the brain lies the white matter,  composed mostly of
axons, or connecting fibers.  We do our computing in the gray matter and
our data transmission in the white matter.  One study of ten people with
bipolar disorder measured gray-matter volume before treatment, then again
after a month of lithium treatment.  In eight of the ten patients, gray
matter volume increased by about 3 percent, equivalent to about five
teaspoons of functional brain.  Further analysis showed that this was a
true increase in neuronal tissue, not related to water retention or a
lithium effect on the MRI image.

Researchers found that the improvement in brain volume brought about by
lithium occurred because lithium increased the production of proteins that
protect brain cells from destruction.

== Lithium Protects the Brain from Dementia ==
So far, lithium is the only substance we know of that enhances the function
of these neuroprotective proteins.  Let's look at the one called bcl-2.
Bcl-2 protects the brain in  two distinct ways.

   - Alzheimer's dementia involves the production in the brain of "gunk"
called amyloid plaque and neurofibrillary tangles .   Bcl-2 and another
neuroprotective protein act to reduce the formation of amyloid plaque and
neurofibrillary tangles.

   - We've written before
(http://www.rienstraclinic.com/newsletter/2007/2007Jan.html#_edn1)that the
stress hormone, cortisol, can have a damaging effect on the brain when
present in excessive amounts.  Bcl-2 protects the brain from this damage,
as well as from damage due to free radicals and radiation.

Researchers looked at 1400 people over the age of sixty and found that
those who were given lithium for other reasons had significantly less
cognitive loss than those who did not take lithium.  While another study
did not confirm this result, the great preponderance of the evidence
indicates that lithium powerfully promotes brain health in many ways.
Let's look at some of those ways.

== Lithium and Depression ==
Not all depression will lift with an anti-depressant drug.  In that case,
psychiatrists will "augment" the anti-depressant drug with another drug.
Lithium has been used for this purpose for over thirty years.  This doesn't
mean that we think that the depressed person has bipolar disorder.  We just
know, based on experience and research, that lithium can also  help with
depression.

Lithium has a favorable effect on the serotonin system, the cortisol
system, and, along with several anti-depressant drugs, it increases
brain-derived neurotropic factor (BDNF).

BDNF is important because even ordinary depression results in shrinkage of
the brain.  The healthy brain produces BDNF which promotes growth and
regeneration of brain cells.  Stress, depression, and aging all decrease
the production of BDNF.

== Lithium and Stroke ==
Lithium does not just promote growth of gray matter.  It has been shown in
animals to promote regeneration of the axon, the long fiber that carries a
nerve signal from one place to another.   In one experiment, researchers
treated a group of rats with lithium for two weeks and compared them to
group not so treated.  In both groups, a major brain artery was blocked to
cause a stroke.  They measured the amount of brain tissue destruction in
both groups, and discovered that the lithium treated group lost less than
half as many brain cells as the untreated group.  They walked better and
suffered fewer coordination problems as a result.

== Adverse Effects of Excessive Lithium ==
So, with all these benefits, why doesn't lithium enjoy a better reputation?
  The trouble is that lithium is best known as a treatment for bipolar
disorder, and many people with that disorder require doses of lithium that
are close to toxic levels. Such individuals need to be carefully monitored
for toxic effects, which can include thyroid and kidney disorders, stomach
upset, tremors, confusion, diarrhea, or lethargy .

But lower doses, the doses normally found in our water and food, can cause
no more trouble than the sodium, vitamin D, and vitamin A found in our
food.  (Each of which, by the way, is toxic in excess, just as lithium is.)

Lithium is a metal, as is iron.  Except for hydrogen and helium, it has the
simplest structure of all the elements.   Our bodies have required it for
millions of years, and our cells contain special structures to pump it
through the membranes.  The question is not "lithium, good or bad?"  but
"lithium, how much?"

There is no generally recognized RDA for lithium, but authorities believe
it to be in the range of one milligram per day.  This contrasts with the 80
to 160 milligrams of elemental lithium (up to 1800 milligrams of lithium
carbonate ) for people with bipolar disorder. Many of the preventive
effects for neurodegenerative disease occur at doses much lower than the
dose used in bipolar disorder.  

== Summary ==
Our daily lithium usually arrives in our grains and vegetables, the amount
varying from place to place due to differing levels of groundwater lithium.
 While lithium has long been known as "the medicine for those crazy
manic-depressive folks," it has important benefits for the brain in
general.  It is life-saving for many people with bipolar disorder and
ordinary depression.   Under a physician's supervision, it can also help
with other neurologic and psychiatric conditions as well.

And George?   Within a month, he stopped the hair-pulling.  While he
continued to be a challenge to his parents, their careful attention to his
diet and to thoughtful limit-setting helped George to become a much happier
and productive young man than most children faced with his initial challenges.

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Note:  A footnoted version of this newsletter appears on our website at
http://www.rienstraclinic.com/newsletter/2007/2007May.html .

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Medicine for People! is written by Douwe Rienstra MD, edited by Carolyn
Latteier, and published at Port Townsend, Washington. Copyright May, 2007.

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