A Potential Explanation of Tourette’s Syndrome

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


(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.