Pathophysiology Of Tourette Syndrome Research Articles

Alpha Melanocyte Stimulating Hormone (MSH) in Tourette's Syndrome

The intermediate lobe of the pituitary is thought to be the primary source of alpha-melanocyte stimulating hormone (alpha-MSH). While the intermediate lobe of the human fetus contains high concentrations of alpha-MSH, the human adult pituitary is devoid of the peptide. Based on evidence implicating the hypothalamus as a site of dysfunction in Tourette's syndrome (TS), and studies suggesting that alpha-MSH may be involved in neuronal maturation, we measured plasma alpha-MSH levels in three unmedicated TS patients (aged 12 to 69), and in three age-matched controls. High plasma alpha-MSH concentrations were detected in all three patients. None of the patients showed any abnormalities in skin coloration. These findings suggest that abnormalities in the synthesis or release of alpha-MSH may be linked to the pathophysiology of TS, and also to the delay in neurodevelopmental maturation.

Opioid modulation of gonadotrophin release in Tourette's syndrome.

Currently the most prevailing hypothesis attempting to explain the pathophysiology of Tourette's syndrome (TS) suggests that the disease results from dopaminergic (DA) hyperactivity (Golden, 1986). Evidence for this hypothesis is indirect and includes the favorable response of these patients to haloperidol, exacerbation of symptoms with dopaminergic drugs (e.g., methylphenidate) and the findings of reduced DA metabolites in the CSF of some TS patients (Singer et al., 1982). We have recently suggested that deranged opioid functions may also be important in the pathophysiology of TS (Sandyk, 1985). Our hypothesis was based on the favorable response of a subgroup of patients to administration of opiate antagonists (e.g., naloxone, naltrexone) (Sandyk et al., 1986), and is also supported by a recent finding demonstrating depletion of striatal dynorphins in a subject with TS (Haber et al., 1986). Furthermore, based on several clinical features of the disease, we have recently suggested that the hypothalamus could be a site of dysfunction in the disease (Sandyk et al., 1986). To investigate the possible role of deranged opioid-mediated hypothalamic functions in TS further, we tested the effects of acute naloxone (Nx) challenge on plasma FSH and LH levels in 5 male TS patients (aged 11-16 years) and in 4 non-TS-diseased controls (narcoleptics). The plasma FSH and LH levels were drawn prior to and 30 min following the intramuscular administration of 1.2 mg of naloxone.

Elevated CSF dynorphin A [1–8] in Tourette's syndrome

A recent neuropathological study has reported decreased levels of dynorphin A immunoreactivity in striato-pallidal fibers in the brain of a patient with severe Gilles de la Tourette's syndrome (TS). This observation, taken with the neuroanatomic distribution of dynorphin and its broad range of motor and behavioral effects, has led to speculation concerning its role in the pathobiology of TS. We report on the presence of elevated concentrations of dynorphin A [1-8] in the CSF of 7 TS patients, aged 20 to 45 years. The increase in CSF dynorphin was found to be associated with the severity of the obsessive compulsive symptoms but not with tic severity in these patients. Although CSF studies lack the precision necessary to address questions of selective involvement of neuronal system in specific CNS locations, these findings suggest that endogenous opioids are involved in the pathobiology of TS and related disorders. Tourette's syndrome (TS) is a chronic neuropsychiatric disorder of childhood onset that is characterized by multiple motor and phonic tics that wax and wane in severity and an array of behavioral problems including some forms of obsessive compulsive disorder (OCD) (1). Once thought to be a rare condition, the prevalence of TS is now estimated to be one case per 1,000 boys and one case per 10,000 girls, and milder variants of the syndrome are likely to occur in a sizeable percentage of the population (2). Although the etiology of TS remains unknown, the vertical transmission of TS within families follows a pattern consistent with an autosomal dominant form of inheritance (3,4). Neurobiologic and pharmacological data have implicated central monoaminergic and neuropeptidergic systems in the pathophysiology of TS, and basal ganglia structures remain the prime candidates as the neuroanatomical origin for TS and related conditions (1). Endogenous opioids, including dynorphin and met-enkephalin are concentrated in structures of the basal ganglia (5), are known to interact with central dopaminergic neurons (6, 7), and may play an important role in the control of motor functions (8). Post-mortem brain studies have directly implicated opioids in the pathophysiology of Parkinson's disease (9), Huntington's disease (10), and most recently in TS (11). The neuropathological study of Haber et al. (11) reported decreased levels of dynorphin A [1-17] immunoreactivity in striatal fibers projecting to the globus pallidus in the brain of a patient with severe TS. This ovservation, taken with the neuroanatomic distribution of dynorphin and its broad range of motor and behavioral effects, has led to speculation concerning its role in the pathobiology of TS.(ABSTRACT TRUNCATED AT 400 WORDS)

Sexual hormones in the pathophysiology of Tourette's syndrome.

The following paper discusses clinical and neurochemical evidence for a role of sexual hormones in the pathophysiology of Tourette's syndrome.

Provocative Drug Testing in Tourette's Syndrome: d- and l-Amphetamine and Haloperidol

Tourette's syndrome (TS) has become the focus of more intensive investigation in recent years as a model neuropsychiatric disorder with precisely defined clinical diagnostic criteria and symptoms which are often responsive to pharmacotherapeutic intervention. In this provocative study, six TS patients were given doses of d-amphetamine, l-amphetamine, and haloperidol, in order to evaluate whether acute drug administration might provide a means of further clarifying the neurochemical pathophysiology of TS. Our patients experienced a heterogeneous array of responses, which precluded inferences regarding the neurochemistry of TS. Our results, however, illuminated many of the difficulties which confront investigators wishing to do behavioral pharmacologic research with TS patients, and provided insight into the complex nature of this neurobehavioral disorder.

Gilles de la Tourette syndrome after long‐term chlorpromazine therapy

Following 6 years of continuous chlorpromazine therapy for schizophrenia, a young woman developed multifocal tics and vocalizations characteristic of Tourette syndrome. The symptoms first appeared when chlorpromazine was withdrawn. They were permanent, although partially ameliorated by chronic haloperidol therapy. Because of her age and past history, these symptoms were attributed to chronic neuroleptic therapy analogous to neuroleptic-induced tardive dyskinesia, rather than to Tourette syndrome per se. These symptoms suggest that chronic receptor-site blockade can result in hypersensitivity of dopamine receptor sites, and that this may play a role in the pathophysiology of Gilles de la Tourette syndrome. This is the first evidence that hypersensitivity of dopamine receptors is involved in the pathophysiology of Tourette syndrome.