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Biomedical subjects

Jürgen-Christian Krieg

Publications and source records attributed to Jürgen-Christian Krieg.

At least 19 recordsLinked to original sources
PubMed2006

Immune-endocrine host response to endotoxin in major depression.

OBJECTIVE: An impaired hypothalamic-pituitary-adrenocortical (HPA) function is a well-established finding in major depression (MD), but it is still unclear how this dysfunction affects immune responses in this disorder. METHOD: To further examine the relationship between immune and endocrine responses in MD, 0.4ng/kg body weight endotoxin [LPS] or 100mug hCRH were sequentially applied to 12 patients with MD and to 12 age- and gender-matched healthy controls after pre-treatment with 1.5mg dexamethasone (DEX). Immune (TNF-alpha, IL-6, rectal temperature) and endocrine (ACTH, cortisol) parameters were examined as area under the curve (AUC) levels. RESULTS: After pre-treatment with DEX, LPS evoked an immune response in all participants of the study with most immune parameters significantly related to the endotoxin challenge. However, only a marked immune response resulted in an additional endocrine reaction. Subsequently, the quantitative extent of the endocrine reaction was related to the extent of the immune response after DEX/LPS challenge. Pre-LPS AUC levels of cortisol, ACTH and post-LPS levels of IL-6 as well as the post-CRH AUC levels of cortisol and ACTH were related to the depressive symptomatology as measured by the Beck depression inventory (BDI). In depressive patients who showed increased cortisol plasma levels before LPS, the later increase in IL-6 was reduced. CONCLUSIONS: The challenge with DEX/LPS did not reveal major impairments of evoked immune functions in MD. Only the endocrine parameters and the IL-6 response were related to the depressive symptomatology, suggesting a limited interaction between immune and endocrine dysfunctions in MD.

Adrenocorticotropic Hormone↗
PubMed2006

Effects of oxidative challenge and calcium on ATP-levels in neuronal cells.

BACKGROUND: Neurocellular overload with hydrogen peroxide (H2O2) induces oxidative stress and may initiate a cascade of intracellular toxic events leading to energy failure, increased lipid peroxidation and subsequently cell death. Studies suggest that hippocampal neurons may be more vulnerable to oxidative stress than cortical cells pointing to a differential vulnerability of neuronal cells. Since disturbed ATP- and calcium (Ca2+)-metabolism may be involved in this process, we here evaluated the effects of H2O2-induced oxidative stress and the involvement of Ca2+-regulation on neuronal energy metabolism. METHODS: Using primary cortical and hippocampal neurons as well as immortalized hippocampal HT22 cells, we determined ATP-levels and accompanying cell death after oxidative challenge with H2O2. Additionally, the combined effects of H2O2 and alterations in Ca2+-concentrations were pharmacologically characterized in more detail. RESULTS: H2O2-incubation decreased ATP-levels in a dose- and time-dependent manner in all neuronal cell systems tested. Such effects were most pronounced in primary hippocampal neurons. In cortical cells, increased ATP-levels were notable under low H2O2-concentrations. A dose-dependent decrease in ATP-concentrations was observed after treatment with Ca2+, which was further enhanced by additional H2O2-challenge. CONCLUSIONS: Our data underline that both, H2O2- and Ca2+-treatment, are able to disturb intracellular energy metabolism. Out of the different systems studied, the ATP-decrease is most pronounced in hippocampal primary neurons, suggesting that this mechanism contributes to the selective neuronal vulnerability to oxidative stress in these neurons.

Adenosine Triphosphate↗
PubMed2006

Sleep deprivation and pain perception.

Chronically painful conditions are frequently associated with sleep disturbances, i.e. changes in sleep continuity and sleep architecture as well as increased sleepiness during daytime. A new hypothesis, which has attracted more and more attention, is that disturbances of sleep cause or modulate acute and chronic pain. Since it is well-known that pain disturbs sleep the relationship between the two has since recently been seen as reciprocal. To fathom the causal direction from sleep to pain we have reviewed experimental human and animal studies on the effects of sleep deprivation on pain processing. According to the majority of the studies, sleep deprivation produces hyperalgesic changes. Furthermore, sleep deprivation can interfere with analgesic treatments involving opioidergic and serotoninergic mechanisms of action. The still existing inconsistency of the human data and the exclusive focus on REM sleep deprivation in animals so far do not allow us to draw firm conclusions as to whether the hyperalgesic effects are due to the deprivation of specific sleep stages or whether they result from a generalized disruption of sleep continuity.

Animals↗
PubMed2005

Interleukin-6 induces glutathione in hippocampal cells.

The cytokine interleukin-6 (IL-6) increases the levels of the physiological antioxidant glutathione (GSH) in peripheral organ systems such as liver tissue. Only little evidence exists about the actions of this cytokine on GSH in neuronal cell systems despite its possible neuroprotective effects. Therefore, we here characterized the effects of IL-6 on GSH in clonal hippocampal HT22 cells and in rat neuronal primary hippocampal cells. Our results demonstrate significant increases of GSH under most conditions after treatment with IL-6 in a time range of 1 to 48 h (HT22 cells) and 1 to 72 h (primary rat neuronal hippocampal cells). Further studies with an IL-6 antibody strongly support the specificity of the effects. These results suggest that IL-6 plays a substantial role in the regulation of GSH in hippocampal cells.

Analysis of Variance↗
PubMed2005

Antioxidative and steroid systems in neurological and psychiatric disorders.

A large number of neurological and psychiatric diseases like Morbus Parkinson, amyotrophic lateral sclerosis, dementia, schizophrenia and probably also affective disorders show an enhanced production of reactive oxygen species. Moreover, alterations of antioxidative systems and beneficial effects of antioxidative substances including steroid compounds such as estrogens have been described in several of these diseases. This review focuses on alterations of antioxidative systems in the course of neurological diseases and psychiatric disorders and on the differential effects of steroids on these systems in the central nervous system. Moreover, a possible clinical relevance of alterations of circulating steroids and of steroid treatment under these conditions is discussed.

Animals↗
PubMed2005

Clozapine-induced weight gain: a study in monozygotic twins and same-sex sib pairs.

To assess the relative contribution of genetic factors in antipsychotic-induced weight gain, we explored the similarity in body mass index (BMI) (kg/m(2)) change under clozapine only (clozapine DeltaBMI) and upon additional inclusion of BMI change under prior antipsychotic medication (total DeltaBMI) of five monozygotic twins in comparison with seven same-sex sibs. Twin and sib pairs were identified by a telephone screening of 786 office-based psychiatrists. Measured data on weight and other clinical variables were obtained cross-sectionally and retrospectively from medical records. We found greater similarity in total DeltaBMI in monozygotic twins (intrapair difference 2.78+/-3.41 kg/m(2)) than in same-sex sibs (5.55+/-4.35 kg/m(2)), resulting in heritability estimates of h(2)=0.8 and A=0.45 (ACE twin model). However, intrapair differences in clozapine DeltaBMI were similar between twins (4.18+/-4.27 kg/m(2)) and sibs (4.68+/-4.88 kg/m(2)). We hypothesize that the weight plateau achieved under clozapine is influenced by genetic factors. The weight gain achieved during pretreatment with other antipsychotics seems to limit clozapine-induced weight gain, thus presumably explaining why heritability/similarity in monozygotic twins in comparison with same-sex sibs is greater for total DeltaBMI than for clozapine DeltaBMI. An important caveat is that, owing to the sample size, the heritability estimates have a large standard error and thus have to be interpreted with caution.

Adolescent↗
PubMed2004

Effects of clozapine and its metabolites on the 5-HT2 receptor system in cortical and hippocampal cells in vitro.

PURPOSE: The goal of the present study was to determine the effects of clozapine (Cloz) and its metabolites norclozapine (Norcloz) and clozapine-N-oxide (Cloz-N-oxide) on the 5-HT(2) receptor system on the levels of protein and gene expression in in vitro systems of primary cortical cells of the rat and human hippocampal SHS5Y5 neuroblastoma cells. METHODS: Clinically relevant concentrations of Cloz (200/400 ng/ml) and its metabolites (200 ng/ml) were used for the examination of the effects of Cloz and its metabolites on serotoninergic 5-HT(2) receptor parameters (density, affinity and mRNA levels) as well as on glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA levels in primary cortical cells of the rat after treatment for 24 h under in vitro conditions. To compare the results to human cells, we also measured treatment-induced changes in 5-HT(2) and GAPDH mRNA levels in human hippocampal SHS5Y5 cells. RESULTS: A significant decrease was found in primary cortical cells for 5-HT(2) receptor density (Cloz 200/Cloz 400/Norcloz 200 and Cloz-N-oxide 200 vs. control) and 5-HT(2A) receptor mRNA levels (Cloz 200 vs. control). 5-HT(2A) receptor mRNA levels were also significantly reduced (Norcloz 200 vs. control) in SHS5Y5 cells. GAPDH mRNA levels were not affected. CONCLUSIONS: The results of the present study show that Cloz and Norcloz induce significant alterations on the 5-HT(2) receptor system in primary cortical cells of the rat and in human hippocampal cells.

Analysis of Variance↗
PubMed2004

Sleep in eating disorders.

Sleep research on eating disorders has addressed two major questions: (1) the effects of chronic starvation in anorexia nervosa and of rapidly fluctuating eating patterns in bulimia nervosa on the sleep regulating processes and (2) the search for a significant neurobiological relationship between eating disorders and major depression. At present, the latter question appears to be resolved, since most of the available evidences clearly underline the notion that eating disorders (such as anorexia and bulimia nervosa) and affective disorders are two distinct entities. Regarding the effects of starvation on sleep regulation, recent research in healthy humans and in animals demonstrates that such a condition results in a fragmentation of sleep and a reduction of slow wave sleep. Although several peptides are supposed to be involved in these regulatory processes (i.e. CCK, orexin, leptin), their mode of action is still poorly understood. In opposite to these experimentally induced sleep disturbances are the findings that the sleep patterns in eating disorder patients per se do not markedly differ from those in healthy subjects. However, when focusing on the so-called restricting anorexics, who maintain their chronic underweight by strictly dieting, the expected effects of malnutrition on sleep can be ascertained. Furthermore, at least partial weight restoration results in a 'deepening' of nocturnal sleep in the anorexic patients. However, our knowledge about the neurobiological systems (as well as their circadian pattern of activity) that transmit the effects of starvation and of weight restoration on sleep is still limited and should be extended to metabolic signals mediating sleep.

Anorexia Nervosa↗
PubMed2004

Lack of association between the -759C/T polymorphism of the 5-HT2C receptor gene and clozapine-induced weight gain among German schizophrenic individuals.

Weight gain is a major side effect of treatment with clozapine and other antipsychotics. Recent studies suggest an important role of the serotonin type 2C receptor gene (5-HT2CR) in antipsychotic-induced weight gain. However, investigations pertaining to a possible association between a -759C/T polymorphism (C allele) of the 5-HT2CR and weight gain induced by clozapine and/or other antipsychotics have yielded inconsistent results. We investigated the -759C/T polymorphism of the 5-HT2CR in relation to clozapine-induced change in body mass index (BMI) (kg/m) in 97 German patients with schizophrenia and found no association between the -759C allele and weight gain after 12 weeks of clozapine treatment. In addition, confounding effects of initial BMI, age, sex and duration of illness on change in BMI could not be detected by multiple linear regression analysis. Our data do not support an involvement of the -759C/T polymorphism of the 5-HT2CR in clozapine-induced weight gain in German patients with schizophrenia. Further pharmacogenetic studies pertaining to antipsychotic-induced weight gain are warranted.

Adolescent↗
PubMed2004

The effect of sleep deprivation on pain.

Chronic pain syndromes are associated with alterations in sleep continuity and sleep architecture. One perspective of this relationship, which has not received much attention to date, is that disturbances of sleep affect pain. To fathom this direction of cause, experimental human and animal studies on the effects of sleep deprivation on pain processing were reviewed. According to the majority of the studies, sleep deprivation produces hyperalgesic changes. Furthermore, sleep deprivation can counteract analgesic effects of pharmacological treatments involving opioidergic and serotoninergic mechanisms of action. The heterogeneity of the human data and the exclusive interest in rapid eye movement sleep deprivation in animals so far do not allow us to draw firm conclusions as to whether the hyperalgesic effects are due to the deprivation of specific sleep stages or whether they result from a generalized disruption of sleep continuity. The significance of opioidergic and serotoninergic processes as mediating mechanisms of the hyperalgesic changes produced by sleep deprivation are discussed.

Analgesics, Opioid↗
PubMed2003

Pharmacokinetics of clozapine and its metabolites in hippocampal HT22 cells.

Up to now, it is not yet clear whether and how clozapine and its metabolites are metabolized in neuronal cells. The interconversion of clozapine and its metabolites, clozapine-N-oxide and norclozapine, was studied in the hippocampal neuronal in vitro system of HT22 cells. Clinically relevant concentrations of clozapine (200+400 ng/ml) and its metabolites (100+200 ng/ml) were used for the examination of the metabolizing effects after short- (4 h) and long- (24 h) term incubation. Two-way analysis of variance revealed a significant decrease of clozapine (P<0.01) and norclozapine (P<0.01) levels in the supernatants of HT22 cells after the treatment procedures. Student-Newman-Keuls tests showed a significant decrease of clozapine 400 after 24 h of incubation (P=0.01) as well as of all concentrations of norclozapine. No significant treatment effects were found for the clozapine-N-oxide degradation. Using semi-quantification by reverse transcriptase-polymerase chain reaction methods, we could show a significant increase of cytochrome P450 (CYP) 1A2 mRNA levels (P<0.05) after clozapine treatment with 200 ng/ml. The results of the present study strongly suggest that clozapine and norclozapine are metabolized in hippocampal neuronal HT22 cells by CYP1A2, whereas the levels of clozapine-N-oxide were not affected. Moreover, CYP1A2 mRNA levels were significantly changed by incubation with clozapine 200.

Analysis of Variance↗
PubMed2003

On episode sensitization in recurrent affective disorders: the role of noise.

Episode sensitization is postulated as a key mechanism underlying the long-term course of recurrent affective disorders. Functionally, episode sensitization represents positive feedback between a disease process and its disease episodes resulting in a transition from externally triggered to autonomous episode generation. Recently, we introduced computational approaches to elucidate the functional properties of sensitization. Specifically, we considered the dynamics of episode sensitization with a simple computational model. The present study extends this work by investigating how naturally occurring, internal or external, random influences ("noise") affect episode sensitization. Our simulations demonstrate that actions of noise differ qualitatively in dependence on both the model's activity state as well as the noise intensity. Thereby induction as well as suppression of sensitization can be observed. Most interestingly, externally triggered sensitization development can be minimized by tuning the noise to intermediate intensities. Our findings contribute to the conceptual understanding of the clinical kindling model for affective disorders and also indicate interesting roles for random fluctuations in kindling and sensitization at the neuronal level.

Electricity↗
PubMed2003

Pain thresholds as a putative functional test for cerebral laterality in major depressive disorder and panic disorder.

OBJECTIVE: Both major depressive disorder (MDD) and panic disorder (PD) exhibit an illness-related functional cerebral laterality with a frontal right/left asymmetry. Using experimental pain lateralization as a putative indicator of functional cerebral laterality, we assessed body side differences in pressure, cold and heat pain thresholds in patients with MDD and PD as well as in healthy control subjects (HC). To control for an attentional bias in perception, reaction times for selective attention were also measured for both visual fields. METHOD: 21 inpatients with MDD, 21 inpatients with PD (DSM-IV diagnosis) and 20 HC subjects, all right-handed, were investigated drug free. Pain thresholds for pressure, cold and heat were assessed at the right and left forearm or hand. A neuropsychological standard test was used to measure selective attention (signal detection, Wiener Testsystem), which allows for the discrimination between left and right visual field stimulus processing. RESULTS: In all participants, a left-sided increased pain sensitivity could be verified by using pressure pain, but not by thermal pain (cold, heat). The diagnosis of MDD or PD had no influence on pain threshold lateralization. There were no differences in reaction times of selective attention between the groups of patients and the HC. Neither did stimulus presentation in the left or right visual field affect reaction time differently. CONCLUSION: Body side asymmetry of pain perception was only found for pressure pain targeting mainly deep tissue (muscle) nociception. This asymmetry, however, cannot be regarded as an indicator of a pathological functional cerebral laterality in MDD and PD.

Adult↗
PubMed2002

Differential effects of antidepressants on glucocorticoid receptors in human primary blood cells and human monocytic U-937 cells.

A number of data support the assumption that antidepressants (ADs) normalize the altered function of the hypothalamic-pituitary-adrenocortical (HPA) system involved in the pathophysiology of depressive disorder via direct effects on glucocorticoid receptors (GRs). In the present study, we examined the tricyclic ADs desipramine (DESI) and imipramine (IMI), the noradrenaline reuptake inhibitor maprotiline (MAPRO), and the noradrenergic and specific serotonergic AD (NaSSA) mirtazapine (MIR) for their effects on GR expression in primary human leukocytes and in monocytic U-937 cells. Semiquantitative RT-PCR indicated that the ADs exert differential effects on GR-mRNA levels in both primary human leukocytes and U-937 cells: whereas MAPRO and IMI did not induce pronounced changes in GR-mRNA levels, DESI and MIR significantly decreased the amounts of GR-mRNA in both cell systems. Further characterization of the effects of MIR revealed a time dependency of the regulation with an initial increase of GR-mRNA levels above control levels after 2.5 h of treatment and a decrease after 4, 24, and 48 h of incubation. A dose-response analysis demonstrated maximal effects of MIR at a concentration of 10(-7) M. Immunohistochemical studies showed that MIR increased the GR protein levels in a time-dependent manner and that this upregulation appeared earlier by additional treatment with dexamethasone (DEX). A translocation of the GR protein from the cytoplasm to the nucleus was induced between 24 and 48 h of treatment with MIR and MIR/DEX, respectively. Taken together, our data further support the assumption that ADs influence the neuroendocrine and immune system via effects on cellular GRs.

Antidepressive Agents↗
PubMed2002

[Coping with illness and the process of dying].

Coping with illness and the process of dying can be interpreted as an antinomy for a physician's work from ancient times. Successful coping is targeted by definition--at least implicitly--on preserving human life at the best quality possible. On the contrary, the process of dying leading to an individual's death remains out of scope. The aim of our study is to describe present concepts concerning the process of dying and successful coping with illness (i.e., with cancer) in order to look for the specific place of competent medical attendance and terminal care within this context.

Adaptation, Psychological↗
PubMed2002

Divided and selective attention in panic disorder. A comparative study of patients with panic disorder, major depression and healthy controls.

OBJECTIVE: While depression is definitely a condition with diminished attentional functioning, there is little evidence as to whether attention is also disturbed in panic disorder. In the present study patients with panic disorder and with depression were compared by means of neuropsychological tests which assess selective and divided attention. METHOD: Twenty-one inpatients with a Panic Disorder, 21 inpatients with a Major Depressive Disorder (DSM-IV diagnoses) and 20 healthy control subjects were investigated drug free. Neuropsychological standard tests were used to measure selective attention (Signal Detection, Wiener-Test-system) and divided attention (Gesichtsfeld-/Neglectprüfung, TAP), which allow the discrimination between left and right visual field stimulus processing. RESULTS: Patients with panic disorder and depression responded significantly slower than healthy control subjects in the test for divided attention, while no differences were found between the two groups of patients. In contrast, there were no differences among the groups of patients and control subjects in regard to reaction time in the test for selective attention. Stimulus presentations in the left and right visual fields did not affect the reaction times differently. CONCLUSIONS: Patients with panic disorder appeared as disturbed in their attentional functioning as patients with depression. Therefore, ignoring attentional deficits in patients with panic disorder is not justified.

Adult↗
PubMed2002

Encephalomyelitis disseminata: a rare, but challenging differential diagnosis of anorectic disorder.

The frequent occurrence of psychiatric syndromes in encephalomyelitis disseminata is known to obscure its diagnosis. We here report on the case of a 19-year-old female patient presenting symptoms of anorexia nervosa and subsequently diagnosed as suffering from encephalomyelitis disseminata. High dose corticoid treatment resulted in a nearly complete remission of the neurological symptoms as well as the normalization of her eating behaviour. Our case report underscores the importance of considering 'organic' aetiology in patients with symptoms of distinct eating disorders. The clinical course confirms recent findings, suggesting that acute inflammation in encephalomyelitis disseminata may induce behavioural symptoms, which precede the onset of neurological signs. To our knowledge, only one previous case has been reported to date.

Adult↗