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Biomedical subjects

S Kasper

Publications and source records attributed to S Kasper.

At least 145 records · Page 8Linked to original sources
PubMed1998

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.

Adult↗
PubMed1998

Effects of tryptophan depletion in drug-free depressed patients who responded to total sleep deprivation.

BACKGROUND: There is some evidence that sleep deprivation (SD) might exert its antidepressant properties by involving serotonergic mechanisms. We investigated the effects of short-term tryptophan depletion (TD) on depressed patients who responded to a single night of total SD. METHODS: Drug-free depressed inpatients (n = 30) were randomly assigned to either TD or sham depletion. Tryptophan depletion was induced by a 24-hour low-tryptophan diet (day 1) followed the next morning by ingestion of a tryptophan-free amino acid mixture (day 2). During sham depletion, the diet and the amino acid beverage were supplemented with tryptophan. Sleep deprivation was performed from day 1 until day 2. Only SD responders received the amino acid beverage the morning after SD. Behavioral ratings and total and free plasma tryptophan levels were obtained before and after the test sessions. RESULTS: Twenty-two of 30 patients showed a favorable outcome after SD. As predicted, TD significantly lowered total and free plasma tryptophan levels, whereas both levels increased during sham depletion. No acute effects on mood were observed during the day after SD in either treatment group. Unexpectedly, TD, but not control testing, prevented the depressive relapse after the recovery night in most of the patients. CONCLUSIONS: Tryptophan depletion did not reverse the antidepressant effects of SD, but it prevented the relapse beyond a night of recovery sleep. These findings suggest that SD does not act via a single monoamine-related mechanism, but they allow the assumption that TD may induce neurochemical alterations that transiently improve depression.

Adult↗
PubMed1998

Effects of tryptophan depletion vs catecholamine depletion in patients with seasonal affective disorder in remission with light therapy.

BACKGROUND: Although hypotheses about the therapeutic mechanism of action of light therapy have focused on serotonergic mechanisms, the potential role, if any, of catecholaminergic pathways has not been fully explored. METHODS: Sixteen patients with seasonal affective disorder who had responded to a standard regimen of daily 10000-lux light therapy were enrolled in a double-blind, placebo-controlled, randomized crossover study. We compared the effects of tryptophan depletion with catecholamine depletion and sham depletion. Ingestion of a tryptophan-free amino acid beverage plus amino acid capsules was used to deplete tryptophan. Administration of the tyrosine hydroxylase inhibitor alpha-methyl-paratyrosine was used to deplete catecholamines. Diphenhydramine hydrochloride was used as an active placebo during sham depletion. The effects of these interventions were evaluated with measures of depression, plasma tryptophan levels, and plasma catecholamine metabolites. RESULTS: Tryptophan depletion significantly decreased plasma total and free tryptophan levels. Catecholamine depletion significantly decreased plasma 3-methoxy-4-hydroxyphenylethyleneglycol and homovanillic acid levels. Both tryptophan depletion and catecholamine depletion, compared with sham depletion, induced a robust increase (P<.001, repeated-measures analysis of variance) in depressive symptoms as measured with the Hamilton Depression Rating Scale, Seasonal Affective Disorder Version. CONCLUSIONS: The beneficial effects of light therapy in the treatment of seasonal affective disorder are reversed by both tryptophan depletion and catecholamine depletion. These findings confirm previous work showing that serotonin plays an important role in the mechanism of action of light therapy and provide new evidence that brain catecholaminergic systems may also be involved.

Adult↗
PubMed1998

Genomic organization and chromosomal localization of the murine epididymal retinoic acid-binding protein (mE-RABP) gene.

The murine epididymal retinoic acid-binding protein (mE-RABP) is specifically synthesized in the mouse mid/distal caput epididymidis and secreted in the lumen. In this report, we have demonstrated by Southern blot analysis of genomic DNA that mE-RABP is encoded by a single-copy gene. A mouse 129/SvJ genomic bacterial artificial chromosome (BAC) library was screened using a cDNA encoding the minor form of mE-RABP. One positive BAC clone was characterized and sequenced to determine the nucleotide sequence of the entire mE-RABP gene. The molecular cloning of the mE-RABP gene completes the characterization of the 20.5-kDa-predicted preprotein leading to the minor and major forms of mE-RABP. Comparison of the DNA sequence of the promoter and coding regions with that of the rat epididymal secretory protein I (ESP I) gene showed that the mE-RABP gene is the orthologue of the ESP I gene that encodes a rat epididymal retinoic acid-binding protein. Several regulatory elements, including a putative androgen receptor binding site, "CACCC-boxes," NF-1, Oct-1, and SP-1 recognition sites, are conserved in the proximal promoter. Analysis of the nucleotide sequence of the mE-RABP gene revealed the presence of seven exons and showed that the genomic organization is highly related to other genes encoding lipocalins. The mE-RABP gene was mapped by fluorescent in situ hybridization to the [A3-B] region of the murine chromosome 2. Our data, combined with that of others, suggest that the proximal segment of the mouse chromosome 2 may be a rich region for genes encoding lipocalins with a genomic organization highly related to the mE-RABP gene.

Amino Acid Sequence↗
PubMed1998

[Effects of electroconvulsive therapy on cognitive functions in therapy-refractory depression].

Within the context of an extensive study of electroconvulsive therapy at the Psychiatric Clinic of the University of Bonn 15 patients suffering from therapy-resistant Major depression (DSM III-R) were examined with a detailed psychometric test battery, containing memory- and nonmemory tests. The test battery had been applied short time before, during and after the treatment with 10 ECT applied unilateral over the nondominant hemisphere. Comparing the test performances before and 1-2 days after the end of the series there were only few remarkable changes: a significant decrease was diagnosed exclusively in 30 min delayed recall of verbal items, while visual short-term memory and visual-constructive performance showed a significant improvement (in spite of unilateral stimulation on the right side). None of the other cognitive functions inclusively speed of performances and reaction time was detracted short time after the end of the ECT-treatment, instead all the measures improved albeit not significantly. Between responders to treatment (50% improvement in HAMD) and non-responders no significant differences neither before nor after the treatment were detected. The non-responders had in nearly all of the tests some better (but not significantly) results despite being older than the group of responders.

Adult↗
PubMed1998

Sertindole and dopamine D2 receptor occupancy in comparison to risperidone, clozapine and haloperidol - a 123I-IBZM SPECT study.

The striatal D2 dopamine binding was studied in schizophrenic patients treated with the novel atypical antipsychotic drug sertindole (n=10). Comparisons were obtained with haloperidol (n=8), clozapine (n=6), risperidone (n=11) and untreated healthy controls (n=8) of a dataset which has partly been reported previously. 123I-Iodobenzamide (IBZM) single photon emission computerized tomography (SPECT) was used for estimation of striatal dopamine D2 receptor binding. Sertindole-treated patients exhibited significantly (P < 0.001) lower levels of striatal D2 binding (BG/FC ratio:1.28) compared with those treated with haloperidol (BG/FC ratio:1.09) and risperidone (8 mg:1.18) but significantly (P < 0.005) higher levels compared with clozapine (BG/FC ratio: 1.49). However, if patients were pretreated with a depot neuroleptic, significantly (P < 0.05) higher striatal D2 binding (BG/FC ratio:1.12) has been obtained. Since sertindole has been shown to exert distinct clinical efficacy for treatment of positive and negative symptoms, our data are indicative that antipsychotic efficacy is not associated with a high degree of striatal D2 receptor occupancy in schizophrenic patients.

Adult↗
PubMed1998

Social phobia: the nature of the disorder.

Social phobia is characterized by a fear of social situations, which are either avoided or endured with intense anxiety or distress. There is a high prevalence of social phobia in the community and the course of the condition tends to be chronic. In spite of the personal impact of social phobia, few sufferers seek professional help. This is due to a lack of awareness about the condition on the part of health professionals and the public. Social phobia demands increased awareness, so that sufferers receive the treatment they need and deserve, so giving them the opportunity to improve their quality of life.

Adolescent↗
PubMed1998

Effects of tryptophan depletion in fully remitted patients with seasonal affective disorder during summer.

BACKGROUND: Deficiencies in brain serotonin function are believed to play an important role in the pathophysiology of seasonal affective disorder/winter type (SAD). However, no direct evidence has been reported so far that lowered brain serotonin activity causes the symptoms of SAD. METHODS: We studied 11 SAD patients who had suffered recurrent winter depressive episodes of SAD and were fully recovered and off treatment during the summer. In a randomized, balanced, double-blind crossover design patients received two amino acid beverages, one containing tryptophan and the other containing no tryptophan but otherwise identical. Behavioural ratings and plasma total and free tryptophan concentrations were assessed at baseline before administration of the amino acid beverages and at several time points afterwards. RESULTS: The tryptophan-free amino acid beverage induced significant decreases of plasma total and free tryptophan levels and both levels increased during sham depletion (condition x time interaction: P < 0.001). Tryptophan depletion, but not sham depletion caused a transient return of depressive symptoms (condition x time interaction: P < 0.001). CONCLUSIONS: The present study demonstrates that SAD patients in remission during the summer are vulnerable to a return of depression when depleted of tryptophan. This finding supports the importance of serotonergic mechanisms in the pathophysiology of SAD.

Adult↗
PubMed1998

Effects of fluoxetine versus bright light in the treatment of seasonal affective disorder.

BACKGROUND: Disturbances of serotonergic neurotransmission appear to be particularly important for the pathophysiology of winter depression. This study investigated whether fluoxetine has antidepressant effects comparable to bright light in the treatment of seasonal affective disorder (winter type). METHOD: A randomized, parallel design was used with rater and patients blind to treatment conditions. One week of placebo (phase I) was followed by 5 weeks of treatment (phase II) with fluoxetine (20 mg per day) and a placebo light condition versus bright light (3000 lux, 2 h per day) and a placebo drug. There were 40 patients (20 in each treatment condition) suffering from seasonal affective disorder (SAD) according to DSM-III-R who had a total score on the Hamilton Depression Scale of at least 16. RESULTS: Forty patients entered phase II and 35 completed it (one drop-out in the fluoxetine group and four in the bright light group). Fourteen (70%) of the patients treated with bright light and 13 (65%) of those treated with fluoxetine were responders (NS). The remission rate in the bright light group tended to be superior (bright light 50%, fluoxetine 25%; P = 0.10). Light therapy improved HDRS scores significantly faster, while fluoxetine had a faster effect on atypical symptoms. Light treatment in the morning produced a significantly faster onset of improvement, but at the end of treatment the time of light application seemed not to be crucial. CONCLUSION: Both treatments produced a good antidepressant effect and were well tolerated. An apparently better response to bright light requires confirmation in a larger sample.

Adult↗
PubMed1998

D2-dopamine receptor occupancy measured by IBZM-SPECT in relation to extrapyramidal side effects.

The purpose of this study was to compare striatal D2 dopamine receptor occupancy of various typical neuroleptics and clozapine in relation to the occurrence of extrapyramidal side effects (EPS). Forty-four inpatients with schizophrenia, including 12 patients with schizodominant schizoaffective disorder, were evaluated using 123I-iodobenzamide (IBZM) and single photon emission computed tomography. Striatal D2 dopamine receptor occupancy was estimated by use of a striatal/frontal cortex ratio (ST/FC) of IBZM binding. Fourteen patients were neuroleptic-free and served as controls. Six patients were treated with clozapine and 24 patients were treated with various typical neuroleptics. ST/FC ratios in patients taking typical neuroleptics were significantly lower than those who were neuroleptic free or treated with clozapine. Patients with EPS had lower ST/FC ratios than those without EPS. A significant linear relationship between ST/FC ratios and severity of EPS estimated by the Simpson-Angus-Scale was established (r=-0.51, p=0.041).

Adult↗
PubMed1998

Mirtazapine in recurrent brief depression.

Recurrent brief depression (RBD) has a high prevalence in the general population (approximately 10%). At present, data on the treatment of RBD are sparse. Results of treatment studies with selective serotonin reuptake inhibitors (fluoxetine, paroxetine) did not demonstrate superiority of the active drug over placebo in RBD. We report about two patients with RBD treated with mirtazapine over a period of 4 months. Mirtazapine is a noradrenergic with specific selective serotoninergic antidepressant. Patients had to keep a diary in order to document psychopathological symptoms of major depression according to DSM-IV. We showed a marked reduction of severity, duration and frequency of brief depressive episodes in two patients with RBD treated with 30 mg mirtazapine over a period of 4 months. Mirtazapine enhances serotonergic as well as noradrenergic neurotransmission. This dual mechanism of action may be necessary to improve RBD. Consequently, mirtazapine might be a treatment option for patients with RBD. However, our preliminary observations need to be substantiated in controlled studies.

Administration, Oral↗
PubMed1998

Side effects, dropouts from treatment and cost consequences.

Estimating the cost of treatment of depression has to take into account the quantifiable direct costs of medication, and hospital and community care, and the indirect costs such as loss of productivity, unemployment, costs of social support, etc. It also has to take into account the intangible costs to the depressed individual which are more difficult to quantify. Depression is a long-term illness and is associated with considerable morbidity and mortality which contribute substantially to the indirect costs of the illness. Successful treatment can be expected to reduce the overall costs of depression to the individual and to society at large. Compliance with treatment is an essential factor in the successful treatment of depression. Meta-analyses of published papers have indicated that significantly more patients discontinue treatment with tricyclic antidepressants due to side effects than with selective serotonin reuptake inhibitors and therefore better tolerated antidepressants should be the first choice of treatment. Pharmacoeconomic studies that take account of the failure of treatment represented by the discontinuations due to side effects show that an apparently cheaper antidepressant like imipramine may turn out to be more expensive than the better tolerated antidepressants.

Antidepressive Agents↗
PubMed1998

Weak antidepressant response after buspirone augmentation of serotonin reuptake inhibitors in refractory severe depression.

Since 1990 open clinical studies and case descriptions reported full or partial antidepressant response after the addition of buspirone to various ongoing antidepressive treatments. Buspirone acts as a partial serotonin agonist at the 5-HT1A receptor. We tried to augment the effect of serotonin-selective re-uptake inhibitors (SSRI) with 30 mg buspirone in a series of 10 in-patients suffering from refractory depression. We observed two cases of partial remission and five other cases with minimal improvement but no case with complete recovery following buspirone augmentation. On the basis of our naturalistic drug surveillance in 10 refractory depressives, we cannot recommend 30 mg-buspirone augmentation of SSRI treatment in severely ill depressives.

Adult↗
PubMed1998

How much do novel antipsychotics benefit the patients?

Although great advances have been made in the pharmacotherapy of schizophrenia, many patients are still not taking full advantage of the beneficial effects of antipsychotic drugs. This is largely a result of the low levels of compliance. Conventional antipsychotics have little efficacy against negative symptoms, and so many patients with schizophrenia are refractory to treatment with these drugs. Additionally, clinically effective doses of conventional antipsychotics can actually aggravate negative symptoms through the development of extrapyramidal symptoms (EPS). Patients taking these drugs, therefore, often felt that the treatment was making them worse instead of better, and were reluctant to continue with it. The novel antipsychotics offer great potential for improving compliance. Clinical trials have shown that atypical drugs such as sertindole do not induce EPS, are effective against negative as well as positive symptoms and do not affect cognition. These observations have been reflected in postmarketing clinical experience, leading to recommendations that novel antipsychotics, such as sertindole, should be prescribed to first-episode patients. These patients would then not experience EPS and would be more likely to continue with their medication in the long term and thus avoid relapse. The major problems affecting compliance with pharmacotherapy for schizophrenia are outlined here showing, by means of case histories, how sertindole has benefited schizophrenic patients.

Adult↗
PubMed1998

Occurrence of trazodone-induced delirium.

Trazodone, a triazolepyridine derivate, is both chemically and pharmacologically distinct from other serotonin reuptake inhibitors and possesses antidepressant, anxiolytic and hypnotic activity. We observed trazodone-induced delirium in three depressed patients who also suffered from preexisting organic cerebral lesions (two cases) or thyroideal dysfunction (one case). The appearance of hallucinations, psychomotoric agitation, and cognitive changes after initiation of trazodone therapy and their prompt cessation after drug discontinuation led to the impression that these were drug-induced phenomena. One possible hypothesis for the observed deliria is an oversensitivity to the effect of meta-chlorphenylpiperazine, which is a metabolite of trazodone with specific 5-HT agonistic properties.

Adult↗
PubMed1998

Pathological regional cerebral blood flow in opiate-dependent patients during withdrawal: a HMPAO-SPECT study.

The aims of the present study were to investigate regional cerebral blood flow (rCBF) in heroin-dependent patients during withdrawal and to assess the relation between these changes and duration of heroin consumption and withdrawal data. The rCBF was measured using brain SPECT with 99mTc-HMPAO in 16 heroin-dependent patients during heroin withdrawal. Thirteen patients received levomethadone at the time of the SPECT scans. The images were analyzed both visually and quantitatively. A total of 21 hypoperfused brain regions were observed in 11 of the 16 patients. The temporal lobes were the most affected area, hypoperfusions of the right and left temporal lobe were observed in 5 and 5 patients, respectively. Three of the patients had a hypoperfusion of the right frontal lobe, 2 patients showed perfusion defects in the left frontal lobe, right parietal lobe and left parietal lobe. The results of the quantitative assessments of the rCBF were consistent with the results of the qualitative findings. The stepwise regression analysis showed a significant positive correlation (r = 0.54) between the dose of levomethadone at the time of the SPECT scan and the rCBF of the right parietal lobe. Other significant correlations between clinical data and rCBF were not found. The present results suggest brain perfusion abnormalities during heroin withdrawal in heroin-dependent patients, which are not due to the conditions of withdrawal.

Adult↗
PubMed1998

Enlarged cerebrospinal fluid spaces in opiate-dependent male patients: a stereological CT study.

Computed tomography was performed in 9 male patients with a diagnosis of opiate dependence and in 9 age-matched psychiatric controls (neurotic depression). Patients with a history or diagnosis of another substance dependence (alcohol, cocaine, cannabis) were excluded from the study. The volumes of internal and external components of cerebrospinal fluid (CSF) were measured with a point-counting stereological method. Analysis of variance with age as a covariate revealed a significant enlargement of external and external CSF spaces in male patients with opiate dependence. There was no significant correlation between the length of opiate dependence and the volumes of internal and external CSF spaces. The present results suggest that opiate dependence is associated with structural brain alterations. However, the relationship between opiate dependence and structural brain changes is complex and still not well understood.

Adult↗