New Explanation of Tourette's Syndrome

James Howard jmhoward at sprynet.com
Tue Jan 13 12:08:53 EST 1998


A Potential Explanation of  Tourette's Syndrome
James Howard

This is designed for consumption by people who have knowledge and/or
experience with  Tourette's syndrome.  (If this interests someone
without these connections to  Tourette's syndrome, I suggest some prior
reading.)  With that in mind, I can make this very brief.  My work,
copyrighted 1985, suggests that the major hormone of the adrenal glands,
dehydroepiandrosterone (DHEA), is necessary for proper growth and
development of all tissues, and maintenance, thereof, following
development, especially the brain.  The other major hormone of the
adrenal glands, cortisol, I suggest works to antagonize the effects of
DHEA.  Therefore, I would label cortisol the primary "anti-DHEA"
hormone.  Currently, there is much study of the connection of cortisol
and DHEA, but the work is backwards to my idea.  That is, searches of
the medical literature will produce much research on  DHEA as the major
"anti-cortisol" hormone.  (In the medical literature, the general term,
"glucocorticoid" is often used in the place of "cortisol," so you might
find references to DHEA as an "anti-glucocorticoid," if you pursue
this.)  While this is important to me and my copyright, I mention this
difference only to demonstrate that a number of investigators think the
connection of DHEA and cortisol is important.  It is important to my
explanation of  Tourette's syndrome.

There are a number of reports in the literature that connect increased
cortisol with  Tourette's syndrome (TS).  No one has studied the levels
of DHEA in this syndrome, so this is my hypothesis regarding TS and
DHEA. Just below is a recent citation that sums up the connection of
cortisol and TS.  For those without the knowledge, you should know that
cortisol production, by the adrenal glands, is stimulated by a cascade
of molecules.  Corticotropin-releasing factor (CSF) stimulates the
release of adrenocorticotropin hormone (ACTH), which travels to the
adrenals and mainly stimulates cortisol production.  (ACTH does
stimulate some production of DHEA, prolactin is more important than
ACTH; more on that below.)  The important statement in this citation is:
"The TS patients had significantly higher levels of CSF CRF than both
the normal controls and the OCD patients."

Biol Psychiatry 1996 May 1;39(9):776-783  "Elevated cerebrospinal fluid
corticotropin-releasing factor in  Tourette's syndrome: comparison to
obsessive compulsive disorder and normal controls"

"Stress- and anxiety-related fluctuations in tic severity are cardinal
features of  Tourette's syndrome (TS), and there is evidence for
involvement of noradrenergic mechanisms in the pathophysiology and
treatment of the disorder. To examine further the pathobiology of this
enhanced vulnerability to stress and anxiety, we measured central
activity of corticotropin-releasing factor (CRF) in patients with TS and
the related condition, obsessive compulsive disorder (OCD). Lumbar
cerebrospinal fluid (CSF) was obtained in a standardized fashion for
measurement of CRF from 21 medication-free outpatients with TS, 20 with
OCD, and 29 healthy controls. The TS patients had significantly higher
levels of CSF CRF than both the normal controls and the OCD patients.
However, there was no difference in CSF CRF between the OCD patients and
the normal controls. Group differences in CSF CRF were unrelated to
current clinical ratings of depression, anxiety, tics, and obsessive
compulsive behaviors. Although the functional significance of this
finding remains to be elucidated, these results are consistent with the
hypothesis that stress-related neurobiological mechanisms may play a
role in the pathobiology of TS."

The investigators, above, also stated that "Stress- and anxiety-related
fluctuations in tic severity are cardinal features of  Tourette's'
syndrome
"  Cortisol is known as the "stress hormone."  Therefore, I
deduce that cortisol has negative effects in TS.  It is known that
cortisol, especially over lengthy time, is a neurotoxin; cortisol is bad
for the brain. 

It has also been found that: "The TS patients secreted significantly
more ACTH than the normal controls in response to the stress of lumbar
puncture."  Biol Psychiatry 1994 Jul; 36(1): 35-43  Remember, CSF
stimulates ACTH, which stimulates cortisol.

Now, my basic principle, that DHEA is the positive hormone and cortisol
is its antagonist, suggests that DHEA should have positive effects
against stress and anxiety.  This has recently been studied and
supported.   "In conclusion, the results presented here show DHEA to be
effective as an antidespair agent in rats with both high anxiety and
despair."  Physiol Behav 1997 Nov; 62(5): 1053-1057   DHEA may alleviate
the stress in TS by increasing the ratio of DHEA to cortisol.

A number of drugs have been used in  Tourette's syndrome.   However,
over time these prove to actually increase tics.  I suggest that the
initial success of these drugs, and their subsequent failure, is due to
positive, then negative, effects on DHEA production.

Mov Disord 1995 Nov;10(6):791-793  "Tardive tourettism after exposure to
neuroleptic therapy"

"A case of neuroleptic-induced adult-onset tardive tourettism is
presented with video documentation. After prolonged neuroleptic therapy,
the patient developed motor and vocal tics at 36 years of age. The tics
were identical to those seen in childhood-onset  Tourette's syndrome.
These cases are rare and have been considered by some to represent
tardive akathisia"

DHEA is significantly low in DHEA (Biol Psychiatry 1973; 6: 23). 
(Please read my explanation of schizophrenia in detail at
http://www.naples.net/~nfn03605.)  Some of the drugs used to treat
schizophrenia have been useful in the treatment of TS.  The drugs used
to control schizophrenia, I suggest, actually exert their effect by
stimulating DHEA production.  That is, "
antipsychotic potencies of most
neuroleptic drugs closely correspond to their prolactin-releasing
potencies at low doses
" (Biol Psychiatry 1990; 27: 1204).  Prolactin is
highly effective at stimulating DHEA production, and, in fact, may be
specific for stimulating DHEA (Am J Ob Gyn 1987; 156: 1275, and
Endocrinology 1985; 117: 1968).  One of these drugs, haloperidol, is
effective in TS (first quotation, below). However, prolonged use of
haloperidol has the negative side effect of increasing tics (second
quotation, below).


Am J Ment Retard 1997 Mar;101(5):497-504  " Tourette's syndrome
associated with mental retardation: a single-subject treatment study
with haloperidol"

"A Tic Checklist and direct observation tic measurement procedure were
developed for the assessment of  Tourette's syndrome in individuals with
mental retardation. Using a single-subject reversal design, we applied
this assessment method to the evaluation of haloperidol treatment for a
subject with  Tourette's syndrome and severe mental retardation.
Relative to baseline, haloperidol 10 mg/day produced decreases of 66% in
simple motor tics, 46% in complex motor tics, 45% in simple vocal tics,
and 50% in complex vocal tics. Improvement was also seen in careprovider
ratings of tic severity, hyperactivity, and compulsive behaviors."

Aust N Z J Psychiatry 1996 Jun;30(3):392-396  "Tics status"

"OBJECTIVES: To describe two patients with tics status, propose a
definition of this syndrome and draw attention to its clinical
significance. METHOD: Two patients suffering from  Tourette's Syndrome
who had developed episodes of continual motor tics that lasted from
minutes to hours, were non-suppressible and intruded into normal
functioning, were treated with an increase in the dose of haloperidol,
in one case with the addition of clonazepam. RESULTS: The offset of the
episodes was gradual and the tic disorder was worse after the episodes.
One patient had further spontaneous episodes of tics status.
CONCLUSIONS: The recognition of tics status has implications for the
management as well as our understanding of the pathobiology of tics and 
Tourette's Syndrome. The definition of tics status should be
standardised."

Nicotine has also been found to be useful, again for a limited time, in 
Tourette's syndrome.  Smoking, i.e., nicotine, increases the production
of DHEA. 

J Steroid Biochem Mol Biol 1993 Aug;46(2):245-251  "Cigarette smoking is
associated with elevated adrenal androgen response to
adrenocorticotropin"

"Cigarette smoking alters the pattern of endogenous steroid levels. We
examined this phenomenon in two separate male groups. Group A consisted
of 189 dyslipidemic men participating in the Helsinki Heart Study and
group B of 100 men including patients with heart disease and healthy
controls. The subjects in the latter group underwent ACTH-testing. In
group A, smokers had significantly higher basal androstenedione and
dehydroepiandrosterone sulfate (DHEAS) levels and
androstenedione/cortisol ratios than nonsmokers. Mean concentrations of
cortisol, dehydroepiandrosterone (DHEA), androstanediol glucuronide,
testosterone, and sex-hormone binding globulin (SHBG) did not differ
between smokers and nonsmokers. In group B, smokers had lower high
density lipoprotein (HDL)-cholesterol and apolipoprotein AI and higher
triglyceride levels than nonsmokers. Basal androstenedione and ACTH
stimulated androstenedione and DHEA concentrations were higher in
smokers. No significant differences were found in basal insulin, SHBG,
estrone, estradiol, testosterone, free testosterone, and
dihydrotestosterone concentrations between smokers and nonsmokers. These
results suggest that smoking decreases the activity of either 21- or 11
beta-hydroxylase in the adrenal cortex, which results in increased
secretion of adrenal androgens."

Psychol Med 1997 Mar;27(2):483-487  "Differential effects of transdermal
nicotine on microstructured analyses of tics in  Tourette's syndrome an
open study"

"BACKGROUND: The treatment of  Tourette's syndrome (TS) is often
unsatisfactory. However, there is some evidence that transdermal
nicotine patch (TNP) application may improve tics of nonsmoking TS
patients who are refractory to haloperidol treatment. METHODS: In this
open study we applied two 10 mg TNP for 2 consecutive days to four TS
patients whose symptoms were not controlled by haloperidol and to a
never-medicated TS patient, all of whom are non-smokers. The Yale Global
Tic Severity Scale (YGTSS) and a quantified video-taped micro-structured
analysis of tics (head-shake tics, eye-blinks, vocal tics, facial
grimace and other body tics) were both carried out to assess the change
after the application of TNP. RESULTS: TNP application significantly
reduced the YGTSS by an average of 50%, with no reported side-effects,
for up to 4 weeks but not 16 weeks, as compared with TNP-free period.
Consistent with these results, the total counts of tics also showed a
significant decrease for up to 4 weeks after the TNP application.
CONCLUSION: TNP application differentially affected individually
quantified tics, which may suggest a differential role of nicotinic
receptors in the generation of different tics."

Haloperidol and nicotine both reduced tic severity.  However, both of
these drugs were useful for a limited time.  My explanation of 
Tourette's syndrome is that these individuals produce more cortisol than
they should, and are limited in their ability to produce DHEA.  If this
is true, then the use of these two drugs, that stimulate DHEA
production, may overwhelm the ability of the adrenal glands to produce
DHEA.  That is, they stimulate DHEA for some time, then the ratio of
cortisol to DHEA may actually increase.  The tics that haloperidol
eventually causes may actually result from reduced availability of DHEA
for certain parts of the brain that cause the tics, characteristic of
prolonged haloperidol use.  I have developed an explanation of epilepsy
that suggests that epileptic seizures occur to increase DHEA.  Now, in
the case of haloperidol, only certain parts of the brain may be
affected, and the tics may represent small seizures, the purpose of
which is to stimulate DHEA.  It is known that tics are sometimes
misdiagnosed as seizure activity.  (You may read my theory of epilepsy
at http://www.naples.net/~nfn03605.)  (My work also suggests that the
addiction of smoking is due to the DHEA stimulated by nicotine, in
individuals who can continue to produce DHEA with nicotine.)

In my study DHEA, I have found references that show that DHEA is low in
childhood, increases through adolescence to a peak in young adulthood,
around age twenty to twenty-five.  Now,  this means that DHEA increases
from childhood through young adulthood.  This period of increasing DHEA
availability should reduce the symptoms of  Tourette's syndrome in some
individuals, assuming that undue stress is not experienced (increased
cortisol).  This is supported.

J Psychol 1997 Nov;131(6):615-626  "Psychophysiological aspects of 
Tourette's syndrome"

" Tourette's syndrome (TS), once considered a rare disorder, has been
investigated extensively in the last two decades. It is inherited,
usually beginning in childhood, and waxes and wanes, usually decreasing
in frequency and severity in adolescence and early adulthood.
Pharmacotherapy is the usual treatment approach, reducing frequency and
severity of symptoms, but it is not a cure and often has side effects.
Psychological help for people with TS and their families may be needed
for this complex disorder."

It is my hypothesis that  Tourette's syndrome results from too much
cortisol and too little DHEA.  I suggest that children with TS might
benefit from supplemental DHEA.  
James Howard

(I do not sell any product, service, or book, nor am I associated in any
manner or form with any entity, person, corporation, company, etc., that
does.)



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