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Biomedical subjects

R Rupprecht

Publications and source records attributed to R Rupprecht.

At least 55 records · Page 3Linked to original sources
PubMed2001

Attenuation of HPA axis hyperactivity and simultaneous clinical deterioration in a depressed patient treated with mirtazapine.

It has been suggested that hypothalamic-pituitary-adrenal (HPA) system dysregulation plays an important role in the pathophysiology of depression and that normalization of HPA axis hyperactivity precedes successful treatment with antidepressants. We report the case of a 61-year-old patient suffering from a major depressive episode who underwent the combined dexamethasone suppression/CRH stimulation test (DEX/CRH test) before and again after one week of mirtazapine treatment. While the patient showed a marked decrease of cortisol and ACTH secretion during the DEX/CRH test within one week, a pronounced and ongoing deterioration of depressive symptoms with suicidal thoughts occurred that was resistant to antidepressant medication and had to be treated with electroconvulsive therapy. Apparently, mirtazapine rapidly attenuates HPA axis hyperactivity in depressed patients via direct pharmacoendocrinological effects. However, this amelioration of HPA system dysregulation is not necessarily accompanied by clinical improvement.

Adrenocorticotropic Hormone↗
PubMed2000

Lack of association of serotonin-2A receptor gene polymorphism (T102C) with suicidal ideation and suicide.

Serotonergic dysfunction has been implicated in the pathophysiology of affective disorders and suicidality. Especially the density of the 5-HT2A receptor was claimed as being increased in suicidality, proposed as an adaptive upregulation due to reduced serotonergic transmission. Recent studies have shown an association of allele C of the 5-HT2A-T102C polymorphism with suicidal ideation in patients with major depression. The purpose of this study was to test whether this proposed marker indicates susceptibility not only to suicidal ideation in depressed patients but also to suicidality as a syndrome. We investigated the 5-HT2A-T102C polymorphism in 131 suicide victims with unknown underlying psychiatric diagnoses, 84 patients with major depression with or without suicidal ideation, and 125 healthy controls. We were unable to find any association of genotype or allele frequencies to major depression, suicidal ideation, or suicide as a syndrome. Thus, our results suggest that this polymorphism may not commonly be involved in the susceptibility to suicidality. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:831-835, 2000.

Adult↗
PubMed2000

Evidence for an association between a G-protein beta3-gene variant with depression and response to antidepressant treatment.

Abnormal signal transduction pathways have been implicated in the pathogenesis of bipolar disorder and major depression. G-proteins are key elements of these pathways in the regulation of cellular responses by transmission of signals from receptors to effector proteins. In recent years several studies have reported altered levels and activities of G-protein alpha subunits in depressive patients. A recently identified polymorphism of a G-protein beta3 subunit (C825T) has been shown to be associated with increased signal transduction and ion transport activity. Therefore, we investigated whether this Gbeta3 polymorphism is associated with affective disorders or with the response to antidepressant treatment in 88 depressive patients (10 bipolar disorder, 78 major depression) compared with 68 schizophrenic patients and 111 healthy controls. We found a significantly higher frequency of the T allele in depressive patients than in healthy controls (genotype: chi2 = 9.571, df = 2, p = 0.008; alleles: p = 0.004, OR = 1.87, 95% CI 1.23-2.84; Fisher's exact test, two sided) and schizophrenic patients (genotype: chi2 = 8.037, df = 2, p = 0.018; alleles: p = 0.009, OR = 1.94, 95% CI 1.99-3.14; Fisher's exact test, two sided). We also found a statistical significant association between TT homozygosity and response to antidepressant treatment after four weeks (p = 0.01). The results of this study suggest that the investigated G-protein beta3 subunit seems to be a susceptibility factor for major depression and maybe even for bipolar disorder, but not for schizophrenia. Further, the presence of the T allele could be an indicator for treatment response.

Adult↗
PubMed2000

[The state of psychiatry in Ukraine. Psychiatric hospitals in Kiev and Shitomir].

The situation of psychiatric patients in the Ukraine is determined by the financial and economic difficulties of this country. In the larger cities, so-called polyclinics take care of ambulant psychiatric patients. However, no other social psychiatric institutions exist. Here, the modalities of hospital psychiatric treatment are discussed using the psychiatric hospitals in Kiev and Shitomir as examples. Undertreatment is also a problem, because only a few psychopharmacological drugs are produced in the Ukraine. Import of new psychopharmacological agents is hampered by economical problems. Improving the availability of psychopharmacological drugs and the establishment of a social psychiatric network are major aims for psychiatrists working in Ukraine.

Commitment of Persons with Psychiatric Disorders↗
PubMed2000

Increased ACTH concentrations associated with cholecystokinin tetrapeptide-induced panic attacks in patients with panic disorder.

Preclinical findings on the role of corticotropin releasing hormone (CRH) in stress and anxiety, on the interaction of CRH and cholecystokinin (CCK) in modulating anxiety, as well as the blunted corticotropin (ACTH) response to CRH in panic disorder suggest that CRH may play a role in panic disorder. To further characterize the role of the hypothalamic-pituitary-adrenocortical (HPA) system in panic disorder, we compared patients with and without CCK tetrapeptide (CCK-4) induced panic attacks. Twenty-four patients with panic disorder were given injections of CCK-4 (25 micrograms). Panic attacks, psychopathological changes, as well as ACTH and cortisol secretion were recorded. Fifteen of the 24 patients experienced a panic attack after CCK-4. ACTH secretion was significantly higher in the patients with CCK-4-induced panic attacks than in those without such attacks. The patients without CCK-4-induced attacks had a brief but less pronounced increase in ACTH concentrations. Cortisol concentrations were not significantly increased after CCK-4 administration. The increased ACTH concentrations suggest that the activation of the HPA system in CCK-4-induced panic attacks plays a physiological role. CRH may be involved in experimentally-occurring and perhaps in naturally-occurring panic attacks as well.

Adrenocorticotropic Hormone↗
PubMed2000

Effects of fluoxetine, indomethacine and placebo on 3 alpha, 5 alpha tetrahydroprogesterone (THP) plasma levels in uncomplicated alcohol withdrawal.

OBJECTIVE: The purpose of this study was to investigate the effects of fluoxetine (F) and indomethacine (I), two drugs that regulate the synthesis of the GABAergic neurosteroid 3 alpha, 5 alpha tetrahydroprogesterone (allopregnanolone, THP) on THP plasma levels and on symptoms of anxiety and depression in alcoholics during ethanol withdrawal. METHOD: Patients who met DSM-IV criteria for alcohol abuse were randomly assigned to treatment with F (40 mg/day) plus misoprostol (M) (500 mg/day) or I (100 mg/day) plus M or placebo (PL) plus M. Patients were rated with the Hamilton Anxiety (14-HAS) and Depression (17-HDS) scales on days 1, 5, 7, 15 and 28 of ethanol withdrawal and with a Visual Analogue Scale for Depression (VASD) and a Visual Analogue Scale for Anxiety (VASA) on days 1, 2, 4, 5, 7, 15 and 28 of withdrawal. On the same days a plasma sample was collected to measure the concentrations of THP by means of a very sensitive gas chromatographic mass spectrometric method. RESULTS: During withdrawal at days 1, 2, 4 and 5, THP plasma values were lower and symptoms of anxiety and depression were significantly higher compared to the late withdrawal phase at days 15 and 28. In the F or I treatment, the depression and anxiety score, measured by VASD and VASA, decreased significantly at day 5-7 whereas THP plasma levels significantly increased compared to PL condition CONCLUSIONS: Treatment of alcohol withdrawal either with F or I reduced the extent of anxiety and depression and normalised THP plasma levels that were decreased during withdrawal.

Adult↗
PubMed2000

Treatment of mitral valve prolapse and panic disorder with metoprolol.

The prevalence of mitral valve prolapse (MVP) and panic disorder (PD) has been reported to range from 0-50% depending on the respective diagnostic manuals and described selection criteria. We report the case of a 44-year-old patient suffering from both panic disorder and mitral valve prolapse. While antidepressants did not result in any improvement of panic symptoms, a fast remission was achieved by treating the patient with metoprolol. This case report suggests that betablockers might represent a useful tool in the treatment of panic disorder and mitral valve prolapse.

Adrenergic Uptake Inhibitors↗
PubMed2000

Pharmacological characterisation of cortical gamma-aminobutyric acid type A (GABAA) receptors in two Wistar rat lines selectively bred for high and low anxiety-related behaviour.

Two Wistar rat lines that have been selectively bred for high-anxiety-related behaviour (HAB) and low-anxiety-related behaviour (LAB) in the elevated plusmaze test may be considered as a genetically prone animal model to study the neurochemical correlates of anxiety-related behaviour. Because there are pronounced differences between the two lines both in baseline levels of open-arm exploration in the elevated plus-maze test and in sensitivity to the anxiolytic effects of 1 mg/kg diazepam, we used these lines to investigate the pharmacology of the benzodiazepine binding site and the GABA binding site of cortical GABAA receptors. No difference in characteristics of flunitrazepam, zolpidem or muscimol binding to cortical GABAA receptors could be detected between the two lines. Although there was an increase in the brain concentration of the anxiolytic neuroactive steroid allopregnanolone, a potent positive allosteric modulator of GABAA receptors, both in HAB and LAB animals after a forced swim stress, allopregnanolone concentrations did not differ between the two lines. Moreover, plasma dehydroepiandrosterone (DHEA) concentrations were similar in HAB and LAB animals. We conclude that anxiety-related behaviour and benzodiazepine sensitivity in these rat lines are likely to be independent of the pharmacology of cortical GABAA receptors.

Animals↗
PubMed1999

Dysregulation of the hypothalamo-pituitary-adrenal axis is related to the clinical course of MS.

OBJECTIVE: To investigate whether dysregulation of the hypothalamo-pituitary-adrenal (HPA) axis is related to clinical characteristics in MS. METHODS: The authors performed the combined dexamethasone-corticotropin-releasing hormone test (Dex-CRH test) in 60 MS patients and 29 healthy control subjects. In addition, the short adrenocorticotropic hormone (ACTH) test was performed in 39 consecutive patients. All patients had active disease and none were treated with glucocorticoids, immunosuppressants, or immunomodulators. RESULTS: The patients had an exaggerated rise in plasma cortisol concentrations in the Dex-CRH test (p < 0.05), indicating hyperactivity of the HPA system. The degree of hyperactivity was moderate in relapsing-remitting MS patients (n = 38; area under the time-course curve for cortisol [AUC-Cort] 226.2+/-38.9 arbitrary units [AU], mean +/- SEM), intermediate in secondary progressive MS patients (n = 16; AUC-Cort, 286.8+/-60.2 AU), and marked in primary progressive MS patients (n = 6; AUC-Cort, 670.6+/-148.6 AU). Differences were significant between the three patient groups (p < 0.005), and between control subjects (n = 29; AUC-Cort, 150.8+/-34.1 AU) and each patient group. Indicators of HPA axis activation correlated with neurologic disability (Kurtzke's Expanded Disability Status Scale), but not with the duration of the disease, number of previous relapses, previous corticosteroid treatments, or depressed mood (Hamilton Depression Scale). The ACTH test was normal in 31 of the 33 patients studied. CONCLUSION: HPA axis hyperactivity in MS is related to the clinical type of disease, with a suggestion of increasing HPA axis dysregulation with disease progression.

Adrenocorticotropic Hormone↗
PubMed1999

Po gene expression is modulated by androgens in the sciatic nerve of adult male rats.

The present results show that androgens are able to modulate the Po gene expression in different models. In particular, we have shown that: (1) the messenger for the androgen receptor (AR) is present in the rat sciatic nerve but not in cultured Schwann cells; (2) castration induces a decrease of Po mRNA levels in the sciatic nerve of male rats, which is counteract by the subsequent treatment with dihydrotestosterone (DHT), the 5alpha-reduced metabolite of testosterone; (3) castration is also able to significantly decrease in the sciatic nerve the activity of the enzyme 5alpha-reductase (which converts testosterone into DHT); and (4) DHT is able to stimulate Po gene expression in cultured Schwann cells. These observations seem to indicate that androgens may exert their effect on Po gene expression via indirect mechanisms; modulation of neuronal influences reaching the Schwann cells through the binding of the androgen to the AR present in neurons may be postulated. However, alternative mechanisms may also be taken in consideration. The data presented suggest indeed that androgens might act on Schwann cells via the progesterone receptor (PR) rather than the AR. It has been observed that: (1) the messenger for PR is present in Schwann cells; (2) DHT may activate the transcriptional activity of a PR-responsive gene by binding to the PR; and (3) putative steroid responsive elements have been described in this paper to be present in the Po promoter region.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1999

Concentrations of 3 alpha-reduced neuroactive steroids and their precursors in plasma of patients with major depression and after clinical recovery.

BACKGROUND: There is preclinical and clinical evidence that plasma concentrations of 3 alpha-hydroxy-5 alpha-pregnan-20-one (3 alpha,5 alpha-tetrahydroprogesterone; 3 alpha,5 alpha-THP), a neuroactive steroid that is a positive allosteric modulator of the GABAA receptor, are altered in depression and normalize as a result of antidepressant treatment. However, no data are available on the concentrations of 3 alpha,21-dihydroxy-5 alpha-pregnan-20-one (3 alpha,5 alpha-tetrahydrodeoxycorticosterone; 3 alpha,5 alpha-THDOC), another GABA ergic neuroactive steroid, in depression. METHODS: We studied nine depressed patients before and after treatment with various antidepressants and compared them to healthy matched control subjects. Blood samples were quantified by means of a highly sensitive combined gas chromatography/mass spectrometry analysis. RESULTS: Compared to control subjects, plasma concentrations of 3 alpha,5 alpha-THDOC and its precursor 5 alpha-dihydrodeoxycorticosterone (5 alpha-DHDOC) were increased in depressed patients and were not significantly influenced by antidepressant treatment. However, 3 alpha,5 alpha-THP plasma concentrations were decreased in depression and clinically effective antidepressant treatment was accompanied by an increase of 3 alpha,5 alpha-THP concentrations in these patients. CONCLUSIONS: Our results provide the first evidence for a differential alteration in the plasma concentrations of the 3 alpha-reduced neuroactive steroids 3 alpha,5 alpha-THDOC and 3 alpha,5 alpha-THP in major depression, which is only partially reversed by successful antidepressant treatment.

Adult↗
PubMed1999

[Coincidence of schizophrenia and panic disorder].

The coincidence between panic disorder and depression is a well known phenomenon. However, only few studies investigated the coincidence of panic disorder with schizophrenia. This may in part be explained by the fact that both positive and negative symptoms of schizophrenia may mask the clinical symptoms of a panic disorder. We report on a female patient suffering both from agoraphobia with panic disorder and paranoid schizophrenia according to ICD-10. The productive psychotic symptoms responded well to treatment with a low dose of zotepine, whereas the panic disorder was effectively treated with a combined therapy with imipramine and cognitive behavioral therapy. Although it has to be questioned whether the coincidence between panic disorder and schizophrenia reflects two different diagnostic entities, the occurrence of symptoms of a panic disorder in schizophrenia deserve further attention because these may be treated efficiently by a specific pharmacotherapy and psychotherapy.

Agoraphobia↗
PubMed1999

The GABA(A) receptor antagonist picrotoxin attenuates most sleep changes induced by progesterone.

Progesterone has been shown to exert benzodiazepine-like effects on sleep, which suggests that they are mediated by an agonistic modulation of GABA(A) receptor functioning. To assess the involvement of GABA(A) receptors, we investigated the sleep responses to one dose of the GABA(A) antagonist picrotoxin (1.5 mg/kg) and progesterone (90 mg/kg), administered IP to eight rats alone and in combination, during the first 4 post-injection hours. Compared with vehicle, picrotoxin significantly delayed the latency to non-rapid eye movement sleep (non-REMS) and thereby decreased all sleep states, but barely affected the EEG activity within non-REMS. Progesterone significantly shortened non-REMS latency, increased pre-REMS, depressed low-frequency EEG activity (< or = 8 Hz) and augmented EEG activity in the higher frequencies within non-REMS. Except for the changes in high-frequency EEG activity, picrotoxin attenuated all effects of progesterone. These findings support the notion that GABA(A) receptors play an important role in the sleep effects of progesterone.

Animals↗
PubMed1999

Assessment of neuroleptic-like properties of progesterone.

There is considerable evidence from epidemiological studies that the onset of psychiatric disorders may be related to changes in the secretion of gonadal hormones. For example, the postpartum period appears to be a vulnerable phase for the occurrence of psychiatric disturbances such as dysphoric mood and even severe psychotic disturbances. It has been suggested that a sudden drop in progesterone concentrations may contribute to the development of such disorders. Because the administration of this steroid might be of therapeutic value in psychiatric disturbances, we investigated the behavioral properties of progesterone in the rat to assess putative neuroleptic-like properties of this steroid. Progesterone administration dose-dependently increased the EEG activity during wakefulness in the 10- to 30-Hz frequency bands and decreased locomotor activity. While no anxiolytic activity could be detected in the plus maze, the highest dose of progesterone (90 mg/kg) exerted an inhibitory effect on the conditioned avoidance response. In contrast to haloperidol (0.5 mg/kg), progesterone neither produced catalepsy nor antagonized amphetamine-induced stereotypy. However, both progesterone (10, 30 and 90 mg/kg) and haloperidol (0.1 mg/kg) effectively restored the disruption of the prepulse inhibition (PPI) of the acoustic startle response (ASR) that was evoked by apomorphine (2 mg/kg). In contrast, allopregnanolone (10 mg/kg), one of the main metabolites of progesterone, did not significantly antagonize the effect of apomorphine on the PPI. This behavioral profile of progesterone is compatible with the sedative properties of its metabolite allopregnanolone via the GABAA receptor, but also with the possibility that progesterone itself shares some properties with atypical antipsychotics, which may be relevant for the development and treatment of psychotic disturbances.

Animals↗
PubMed1999

Binding characteristics of the glucocorticoid receptor in peripheral blood lymphocytes in multiple sclerosis.

Although the exact etiology of multiple sclerosis (MS) remains unresolved, immune reactions are believed to be the central pathogenic mechanisms. Endogenous and therapeutic steroid hormones affect the immune system, and inflammatory diseases are associated with activation of the hypothalamic-pituitary-adrenal axis, providing evidence of an immune-endocrine interplay. Function tests in MS have revealed dysregulation of the hypothalamic-pituitary-adrenal system in a substantial proportion of patients. We characterized glucocorticoid receptor (GR) binding in peripheral blood lymphocytes from 39 MS patients and 14 age- and sex-matched controls with respect to dissociation constant and binding capacity, using a whole-cell binding assay with [3H]dexamethasone as the ligand. GR binding parameters did not differ significantly between patients (Kd 8.98 +/- 1.07 nM, Bmax 183 +/- 29.8 fmol/mg) and controls (Kd 9.36 +/- 1.17 nM, Bmax 158 +/- 16 fmol/mg). No effect of age, sex, course, duration or severity of disease, or prior steroid treatments was detected. GR binding parameters were analyzed in relation to the results of the combined dexamethasone-CRH test, which reflects corticosteroid receptor function at the hypothalamus, in 30 patients and 9 controls. While controls showed a moderate correlation between binding affinity of the GR in lymphocytes and regulatory function at the hypothalamic level, the patients did not. These data suggest that the physiological relationship between binding and function of the glucocorticoid receptor is disturbed in MS.

Adolescent↗
PubMed1999

Neuroactive steroids: mechanisms of action and neuropsychopharmacological perspectives.

Steroids influence neuronal function by binding to intracellular receptors that can act as transcription factors and regulate gene expression. In addition, some so-called 'neuroactive steroids' are potent modulators of an array of ligand-gated ion channels and of distinct G-protein coupled receptors via nongenomic mechanisms, and they can influence sleep and memory. This article describes how these neuroactive steroids modulate neurotransmitter receptors and addresses the neuropsychopharmacological potential that arises from the intracellular crosstalk between genomic and nongenomic steroid effects. Neuroactive steroids could also have a role in the response to stress and the treatment of psychiatric disorders, such as depression, and, as they affect a broad spectrum of behavioral functions through their unique molecular properties, they could constitute a yet unexploited class of drugs.

Dehydroepiandrosterone↗