A Potential Explanation of Tourette's Syndrome

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Copyright ã 1997 James Michael Howard, Fayetteville, Arkansas, U.S.A.


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(Some Potential New Support: Biological Psychiatry 2005 (March 15);
57: 667-673: The authors found increased levels of interleukin-12
and tumor necrosis factor alpha in their subjects. DHEA decreases
TNF alpha (Crit Care Med. 2001 Feb;29(2):380-4) and decreases
interleukin-12 (Aliment Pharmacol Ther. 2003 Feb;17(3):409-14). I
suggest it is possible that these findings may be explained by low
levels of DHEA, or interference of available DHEA, in Tourette's
syndrome.)

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 schizophrenia (Biol. Psychiatry 1973;
6: 23). (Please read my explanation of schizophrenia.) 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 standardized."

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 hypothesis of epilepsy.) (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.

Source: http://www.anthropogeny.com/A%20Potential%20Explanation%20of%
20Tourette.htm


Paul Marshall
editor @ tourettes-disorder.com
http://www.tourettes-disorder.com