Copyright ă 1997 James Michael Howard,
(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.