[Tourette's syndrome - a review]. / Das Tourette-Syndrom Eine Ubersicht.

Tourette's syndrome (TS) is a neuropsychiatric disorder characterised by the occurrence of chronic motor and vocal tics that usually begin in childhood. A prevalence of 4-5/10.000 individuals is estimated. Tourette's syndrome patients frequently show comorbidity with other psychiatric disorders such as obsessive compulsive disorder (OCD), attention deficit hyperactivity disorder (ADHD), anxiety, and affective disorders. Some forms of OCD seem to share a common genetic etiology with TS and to be a facultative part of the TS phenotypic spectrum. Based on MRI, positron emission tomography (PET), and single photon emission computed tomography (SPECT), data alterations in the cortico-striato-pallido-thalamo-cortical functional systems have been discussed. Within these systems, dopaminergic neurotransmission is thought to play an important role in the pathophysiology of TS. Autoimmunological mechanisms seem to be important in some subtypes of TS and OCD that are triggered or exacerbated by infections with hemolytic streptococci. In these cases, immune modulatory therapy proved to be efficient. To date, there is no established treatment regimen for TS. The medications used most frequently are antipsychotics.

Study of family history in seasonal affective disorder.

OBJECTIVE: In our investigation we assessed the risk of morbidity for psychiatric disorders among the first-degree relatives of patients with seasonal affective disorders (SAD) and compared it with a control group of patients suffering from nonseasonal mood disorders (NSMD). METHODS: Over a period of 12 months (June 1994 to May 1995) we recruited patients consecutively admitted to our psychiatric university outpatient clinic in a prospective study. All patients were diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, revised 4th edition. A total of 344 patients presented themselves with a diagnosis of affective disorder. Out of these, 36 were diagnosed as having SAD. From the same group of 344 patients, we selected a matched control group of 36 patients suffering from NSMD. The experimental and control groups were matched according to sex, age, severity of illness and number of siblings. RESULTS: There was no significant difference concerning the lifetime prevalences for psychiatric disorders among the fist-degree relatives in both groups (SAD = 16.5% and NSMD = 19%). CONCLUSION: It seems that there is no difference in familiarity for psychiatric disorders between SAD and NSMD.

No change in striatal dopamine re-uptake site density in psychotropic drug naive and in currently treated Tourette's disorder patients: a [(123)I]-beta-CIT SPECt-study.

BACKGROUND: There is evidence that Tourette's disorder (TD) is associated with abnormalities in the dopaminergic system involving the dopamine transporter (DAT). Data from [(123)I]-beta-CIT single photon emission computed tomography (SPECT) studies and postmortem findings concerning DAT densities in TD patients are not conclusive. The objective of our study was to measure DAT densities with [(123)I]-beta-CIT binding in TD patients who were either psychotropic drug naive or currently treated with antipsychotics (AP) and healthy controls. METHOD: Altogether 20 TD patients were investigated. A total of 15 patients were psychotropic drug naive and five were currently treated with AP. Ten psychotropic drug naive patients were compared with ten age and sex matched healthy subjects. Five currently treated patients were compared with five age and sex matched psychotropic drug naive TD patients. The investigation was carried out using [(123)I]-beta-CIT (2-beta-carbomethoxy-3-beta(4-iodophenyl)-tropane and SPECT. Regions of interest (ROI) were drawn over the striatum and the cerebellum. RESULTS: The DAT densities measured by the striatal/cerebellar (S/C) binding ratio did not differ between drug naive TD patients and the controls. The difference between currently AP treated and psychotropic drug naive TD patients did not reach the level of significance. There was no correlation between the ratio and severity of tics and illness. CONCLUSION: Our study with psychotropic drug naive TD patients contributed to clarify the inconsistent results concerning the DAT.

Effective open-label treatment of tourette's disorder with olanzapine.

Olanzapine is an atypical antipsychotic drug which shows a high antagonistic affinity to the D1, D2 and D4 and the 5-HT2A and 5-HT2c receptors. The goal of our investigation was to assess the efficacy of olanzapine in patients with Tourette's disorder who were either antipsychotic naive or who did not tolerate and/or did not respond to previous antipsychotic treatments in an open-label pilot study. Fourteen patients with a mean (SD 12.4) age of 32.6 years were treated for a period of 6 weeks. Seven patients did not respond to, or did not tolerate, previous neuroleptic treatments and seven patients were antipsychotic naive. All patients received olanzapine in ascending dosage, following a washout period of 1 week. Initial dosage was 10 mg/day with a maximum dosage of 20 mg/day. The Yale Global Tic Severity Scale (YGTSS), Fischer Symptom Check List-Neuroleptika and the Clinical Global Impression Severity Scale (CGI) were used. Two of the 14 patients did not complete the investigation. The mean dosage of olanzapine was 15 mg/day (SD 3.3) at day 42 (end of the study). The YGTSS scores and the CGI significantly decreased over the treatment period. The only side-effect observed was mild sedation which decreased during the course of the investigation and two patients had weight gain of 3-5 kg with increased appetite. In our study, we found that olanzapine was a safe and effective treatment alternative to other antipsychotics. In order to confirm these preliminary results, double-blind placebo controlled trials are warranted.

The citalopram challenge test in patients with major depression and in healthy controls.

Neuroendocrine challenge tests in depressed patients have revealed a blunted hormonal reaction to serotonergic stimuli. In the present study, citalopram was chosen as the serotonergic agent for neuroendocrine stimulation. Compared to earlier challenge agents, citalopram has the advantage of serotonergic selectivity, its application is well tolerated and the possibility of intravenous application reduces pharmacokinetic interference. Sixteen patients suffering from an acute episode of major depression and 16 healthy controls underwent the stimulation procedure with 20 mg of citalopram and placebo. Whereas significant differences in the secretion of prolactin and cortisol between citalopram and placebo challenge were observed in the control group, no differences were found in the group of depressed patients. Comparison of depressed patients and controls showed a significantly blunted prolactin secretion in patients. Differences in cortisol secretion following serotonergic stimulation with citalopram did not become significant. The stimulation procedure was well tolerated in all subjects, although a higher number of side effects was observed in the control group. The amount of side effects did not correlate with the hormone responses. These results are in line with the hypothesis of serotonergic hypofunction in depressed patients. In conclusion, the 20-mg citalopram challenge test is thought to be a promising tool for further investigation of serotonergic function in psychiatric illness.

Cerebral CT findings in male opioid-dependent patients: stereological, planimetric and linear measurements.

Cerebrospinal fluid (CSF) space enlargement has been demonstrated in substance-related disorders like alcohol and cocaine dependence. Experimental animal studies showed a reduction in shape and size of mesolimbic dopaminergic neurons after chronic morphine administration. Other studies indicated a change of neurofilament and glial fibrillary acid proteins after chronic opiate administration. Furthermore, frequent overdosing and toxicological effects of 'street'-heroin may lead to CSF space enlargement in opioid dependence. In our study the pericortical and ventricular CSF space of 21 male opioid-dependent patients was compared with an age- and sex-matched normal control group. Considering serious problems with ratio and proportion measures, we used a battery of linear (cella media index, Huckman number, frontal horn index), planimetric (cortical atrophy score) and stereological volumetric measures in order to detect differences in cranial computerized tomography scans. We found a significant ventricular and cortical volume loss of the brain in opioid-dependent patients. A higher degree of frontal lobe volume loss seemed to be associated with a shorter period of abstinence before relapse. However, the etiology of volume loss of the brain in opioid-dependent patients is still unclear, but experimental animal studies provide some evidence that long-term, chronic opiate exposure is associated with visible changes of specific structures in the brain.

Genetic polymorphisms for drug metabolism (CYP2D6) and tardive dyskinesia in schizophrenia.

In the present study, the occurrence of tardive dyskinesia (TD) in chronic schizophrenia patients was investigated in relation to pharmacogenetic polymorphisms. It is known that the metabolism of important neuroleptic drugs is influenced by polymorphisms of the CYP2D6 gene, which encodes the cytochrome P450 enzyme debrisoquine/spartein hydroxylase. Forty-five patients meeting the DSM IV criteria for schizophrenia, chronic course, were recruited. The patients were examined for the mutations CYP2D6*3, CYP2D6*4 and CYP2D6*5. The CYP2D6 genotype distribution in the patient group did not differ from that in healthy Caucasian populations. Tardive dyskinesia was found in 26 patients (57.8%). When comparing patients without CYP2D6 mutations with patients heterozygous for one mutation, we found a higher incidence of TD in the latter (81.3% vs. 46.4%, p = 0.031, multiple regression analysis), which demonstrates a significant influence of the CYP2D6 genotype of the manifestation of TD. As slight differences in the metabolism of drugs in patients heterozygous for CYP2D6 mutations and patients without such mutations are known, we conclude that heterozygous carriers of 2D6 mutated alleles may show an increased susceptibility to developing TD.