Blunted growth hormone response to clonidine in Gilles de la Tourette syndrome.

Noradrenergic mechanisms have been involved in the pathogenesis of Gilles de la Tourette Syndrome (GTS). Since the central alpha 2 adrenergic agonist clonidine is widely used as a therapeutic agent in GTS, the present study aimed at assessing whether GH release after clonidine, representing central alpha 2-adrenergic receptor sensitivity, was altered in GTS. After administration of 2 micrograms/kg body weight clonidine, the GH response was examined in nine drug-free, alcohol-abstinent GTS patients (eight men, one woman) and in nine age- and sex-matched abstinent healthy controls. A blunted response of GH release (< 5 ng/ml) was observed in seven patients and the area under the curve (AUC) of the GH-release was significantly reduced (p < .01) compared to controls. This finding indicates an involvement of the noradrenergic system in GTS.

Investigations of the cellular immunity during depression and the free interval: evidence for an immune activation in affective psychosis.

1. Results of investigations of the immune function in affective disorders are conflicting. Some authors described an immune suppression, others an immune activation in major depression. The authors performed a study of cellular immunity in the MDD subtype endogenous depression. 23 patients suffering from endogenous depression were investigated during the depressive state, the results were compared with a group of 14 patients during the free interval and 51 healthy controls. 2. The lymphocyte proliferation after incubation with diphtheria- and tetanus toxoid, mainly stimulating T-cells, was reduced but after incubation with an antigen-cocktail, stimulating both, T- and B-cells, was increased in patients during depression and during the free interval compared to controls. 3. The CD3(+)- and CD4(+)-cells were significantly enhanced in both groups of patients while the CD8(+)-cells showed no differences to the controls. The ratio CD4+/CD8+ was increased in patients, too, as described in some autoimmune disorders. 4. The suppressor cell activity was significantly reduced in the PWM-assay and in the PHA-assay. The mixed lymphocyte culture showed a tendency to reduced suppressor cell activity as well. 5. The results point to an immune activation and to a disturbed control of the proliferative activity in affective psychosis. A T-cell related defect, not compensated by an increased number of CD3+- and CD4+ -cells is discussed. 6. From our point of view, the conflicting results of psychoneuroimmunological investigations in depressive disorders may be related to etiologically different subgroups of depression. The diagnostic category of MDD is possibly one of the traps in psychoneuroimmunology.

Repeated dexamethasone suppression test during depressive illness. Normalisation of test result compared with clinical improvement.

Serial plasma cortisol concentrations were recorded under controlled conditions after an overnight dexamethasone suppression (DST) in 20 depressed patients with initially abnormal test results. The cortisol levels were related to clinical course. All 20 patients showed normalisation of hypothalamic-pituitary-adrenal (HPA) hyperactivity, a mean of 3.4 +/- 1.8 weeks before clinical recovery was achieved. In 4 clinically remitted patients the endocrine disturbance as evidenced by abnormal DST results preceded a depressive relapse. DST results did not appear to be affected by psychotropic drugs including benzodiazepines.

The lack of effect of bupropion HCL (Wellbatrin) on the secretion of growth hormone and prolactin in humans.

The effect of bupropion HCL (Wellbatrin), a new anti-depressant, on the secretion of GH and PRL in healthy male subjects and male hyperprolactinaemic patients was studied. The study was a randomised double-blind test in which 6 subjects and 6 patients who had been treated with neuroleptics were each, in accordance with the random plan, treated once with placebo and once with 200 mg bupropion p.o.. After administration of the test substance, blood was drawn to measure bupropion, GH and PRL up to 240 minutes thereafter. Neither in the healthy men nor in the patients could a specific effect of bupropion on the secretion of GH be shown in comparison to placebo although bupropion in all subjects and patients was well reabsorbed. As opposed to the results of Stern et al. (5), no change in the secretion of PRL was measured in either the healthy subjects or the hyperprolactinaemic patients. In addition, no change in the TRH-induced stimulation of PRL could be measured. The results of the present study offer no positive contribution towards an explanation of the mechanism of bupropion.

Cellular immunity, HLA-class I antigens, and family history of psychiatric disorder in endogenous psychoses.

We found an increased lymphocyte proliferation after stimulation with an antigen "cocktail" in 49 schizophrenic patients and 37 patients suffering from affective psychosis, compared with 45 healthy control subjects. On the basis of this and other findings such as increased numbers of CD3+ and CD4+ cells, an increased ratio of CD4+/CD8+ cells, and a reduced level of suppressor cell activity in schizophrenia and endogenous depression, we investigated the influence of the human leukocyte antigen-Class I (HLA-A, HLA-B, HLA-C) system on the altered immune function and evaluated the relationship to immune function of a family history of psychiatric disorders. A cluster analysis of cases with regard to the HLA-Class I antigens was first performed in a group of 133 healthy control subjects, and two immunogenetically different clusters were found; then 86 patients (49 schizophrenics, 37 affective psychoses) for whom immune functional data were available were assigned to the two HLA-I clusters that had been determined in the control subjects. Analyses of variance (ANOVAs) showed no differences in immune function between the two clusters. With respect to the cluster assignment and the family history of psychiatric diseases, a two-way ANOVA revealed significant differences in the lymphocyte response to the antigen cocktail, in the number of CD8+ cells, and in one suppressor cell assay. When patients were compared by ANOVA on the basis of family history of psychiatric disorder, patients with a positive family history showed a significantly higher number of CD4+ cells and a higher CD4+/CD8+ ratio. Moreover, certain HLA genes, especially HLA-A1, HLA-B8, HLA-B16, and HLA-C2 seemed to be related to the immune function and/or to the immune function and the family history.

Cellular immunity in schizophrenic patients before and during neuroleptic treatment.

A possible connection between immunological alterations and schizophrenia has been discussed for many years. We studied 55 schizophrenic patients in an acute stage of illness before they began neuroleptic treatment. 35 patients who showed clinical improvement on neuroleptics, and 51 healthy controls. Our interest was focused on parameters of cellular immunity. We found an increased lymphocyte response to stimulation with pokeweed mitogen (PWM) and phytohemagglutinin (PHA) in patients before neuroleptic therapy and also an increased response to stimulation with PWM and PHA during treatment compared to controls. Stimulation with antigens generally showed a lower lymphocyte response in patients than in controls, but the difference was only significant after stimulation with tuberculin before neuroleptic treatment and after stimulation with varidase, diphteria-toxoid, tuberculin, vaccinia, and rubella during neuroleptic treatment. The number of CD3+ and CD4+ cells, but not the number of CD8+ cells, was increased before and during treatment in comparison to controls. Suppressor-cell activity was reduced in three different suppressor cell assays before and during neuroleptic medication compared to controls. We therefore conclude that alterations of the immunological system which are, as has been demonstrated, not due to treatment with neuroleptics might play a role in schizophrenia.

A highly sensitive and precise radioenzymatic assay for plasma epinephrine and norepinephrine.

A modification of the procedures for simultaneous radiometric determinations of plasma epinephrine (E) and norepinephrine (NE) was developed. High performance liquid chromatography (HPLC) is excellently suited to separate the radioactive products of the enzymatic methylation of catecholamines. The time-saving procedure shows significant advantages as against the conventional method of isolating normetanephrine and metanephrine by thin layer chromatography. The high sensitivity (detection limit = 1 pg), specifity, and good precision (cv = 6%) of this assay are demonstrated.

T-cells and psychopathology in schizophrenia: relationship to the outcome of neuroleptic therapy.

Until recently, attention has been focused on the pathogenetic aspects of immunological findings in schizophrenic patients. There has been no mention of the relationship between such findings and schizophrenic symptoms. To study the probable relationship between T-cells and T-cell subgroups in the course and prognosis of schizophrenia, immunological and psychopathological parameters were correlated in 55 patients suffering from schizophrenia (ICD-9: 295.0-295.6) or schizoaffective psychosis (ICD-9: 257.7) before neuroleptic treatment. The correlations were performed for a second time in 24 of these patients after clinical improvement at a reinvestigation. Positive correlations of the Brief Psychiatric Rating Scale and the Scale for Assessment of Negative Symptoms with the numbers of CD3+ and CD4+ T-cells (total T- and T-helper cells), which were enhanced compared with controls, were found at the reinvestigation after clinical improvement, whereas no significant correlation could be detected at the pretreatment investigation. These results show that the cellular immune parameters are related to the course of the psychopathological symptoms in schizophrenia and, possibly, are a marker of the therapeutic outcome or neuroleptic treatment.

Neuroleptic malignant syndrome due to atypical neuroleptics: three episodes in one patient.

Neuroleptic malignant syndrome (NMS) is a rare, but potentially lethal complication of antipsychotic medication. The risk of developing NMS under atypical neuroleptics seems lower than under typical neuroleptics. However, the use of atypical neuroleptics in modern psychopharmacotherapy is increasing, so the incidence of NMS under these drugs may also increase. Here, we will describe three episodes of NMS that fulfilled the DSM-IV criteria for NMS (APA, 1994). The epivodes of NMS occured under treatment with clozapine, risperidone, and amisulpride. These episodes had some atypical features that will be discussed with regard to the pathophysiological mechanisms leading to NMS.