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Biomedical subjects

M Rothermundt

Publications and source records attributed to M Rothermundt.

At least 19 recordsLinked to original sources
PubMed2004

S100B potently activates p65/c-Rel transcriptional complexes in hippocampal neurons: Clinical implications for the role of S100B in excitotoxic brain injury.

Increased serum levels of S100B are positively correlated with multiple forms of CNS damage, such as stroke, CNS trauma and neurodegenerative diseases, but also in psychiatric disorders. However, it is currently not known whether increased serum levels of S100B reflect a neuroregenerative or neurodegenerative response. Since glutamate receptor overactivation (excitotoxicity) may contribute to neuronal pathology in psychiatric disorders, we investigated the effect of S100B on N-methyl-d-aspartate (NMDA)-induced neuronal cell death. Here we demonstrate that very low concentrations of S100B significantly protect primary rat hippocampal neurons against NMDA toxicity by activation of transcription factors of the Rel/nuclear factor kappaB (NF-kappaB) family. Further experiments suggest that i) S100B activated expression of the receptor of advanced glycation products (RAGE) gene in neurons and ii) S100B induced a unique composition of the active NF-kappaB complex consisting of the p65 and c-Rel subunits suggesting a novel mechanism for NF-kappaB activation involved in S100B-mediated neuroprotection. Our data suggest that S100B secreted during the glial response to brain injury potently activates p65/c-Rel in a RAGE-dependent manner and may exert neuroprotective and neuroregenerative effects in psychiatric disorders.

Animals↗
PubMed2004

The impact of the selective monoamine reuptake inhibitors reboxetine and citalopram on visually-evoked event-related potentials in depressed patients.

OBJECTIVE: The aim of our study was to assess the possible relationship between event-related potentials (ERP) and serotonergic or noradrenergic activity in depression. Therefore, we were interested in the impact of different monoamine reuptake inhibitors on ERP. METHODS: Thirty-six inpatients with major depression were treated with either reboxetine (n = 17) or citalopram (n = 19) in a prospective randomized study. Before and after four weeks of treatment, visually-evoked ERP were investigated. Twenty-two patients completed the study. Monoaminergic function was determined by oral reboxetine and citalopram challenge tests. RESULTS: P3 latency significantly decreased after a four-week treatment with either drug. There was no significant difference in the decrease of P3 latency between both drugs. We detected a significant inverse correlation between serotonergic hypofunction before treatment and the P3 latency (r = -0.739, p = 0.001). CONCLUSIONS: These results show that, in depressed patients, the P3 latency is decreased by antidepressive treatment. Furthermore, the results suggest that P3 latency might depend on the serotonergic rather than the noradrenergic system.

Adolescent↗
PubMed2003

[Depressive disorders with somatic illnesses].

Up to 40% of medically ill patients suffer from clinically relevant depressive disorders, of which almost half can be classified as major depression. Some modern medical treatment procedures seem to increase the risk of depression. Quality of life as well as influences detrimental to the course of medical illness can be favourably influenced by a validated diagnostic approach and early careful therapeutic interventions. However, treating depressive disorders does not seem to exert a direct influence on the somatic prognosis. High depressive co-morbidity and burden of illness for both the individual and the society form a stark contrast to the obviously still insufficient diagnostic and therapeutic strategies in daily medical routine.

Attitude to Health↗
PubMed2002

Immunological research in clinical psychiatry: report on the consensus debate during the 7th Expert Meeting on Psychiatry and Immunology.

There is convincing evidence that cytokines are involved in the physiology and pathophysiology of brain function and interact with different neurotransmitter and neuroendocrine pathways. The possible involvement of the immune system in the neurobiological mechanisms that underlie psychiatric disorders has attracted increasing attention in recent years. Thus in the last decade, numerous clinical studies have demonstrated dysregulated immune functions in patients with psychiatric disorders. Such findings formed the basis of the 7th Expert Meeting on Psychiatry and Immunology in Muenster, Germany, where a consensus symposium was held to consider the strengths and weaknesses of current research in psychoneuroimmunology. Following a general overview of the field, the following topics were discussed: (1) methodological problems in laboratory procedures and recruitment of clinical samples; (2) the importance of pre-clinical research and animal models in psychiatric research; (3) the problem of statistical vs biological relevance. It was concluded that, despite a fruitful proliferation of research activities throughout the last decade, the continuous elaboration of methodological standards including the implementation of hypothesis-driven research represents a task that is likely to prove crucial for the future development of immunology research in clinical psychiatry.

Allergy and Immunology↗
PubMed2001

Review of immunological and immunopathological findings in schizophrenia.

The involvement of immunological and immunopathological mechanisms in the etiopathogenesis of schizophrenia has been a matter of research, with recently increasing effort. This article reviews the findings focusing on postmortem neuropathology, the blood-brain barrier, antibodies, acute phase proteins, immunocompetent cells, and activation markers of immunocompetent cells. Evidence for the two primarily postulated hypotheses (the infectious hypothesis and the autoimmune hypothesis) is critically discussed. On the basis of the findings, perspectives for future research are outlined aiming at a precise and consequent strategy to elucidate a potential involvement of immune mechanisms in the etiopathogenesis of schizophrenia.

Humans↗
PubMed2001

Different immune patterns in melancholic and non-melancholic major depression.

The search for immune patterns in major depression has thus far resulted in ambiguous findings, probably because patient samples are psychiatrically heterogeneous. We therefore focused on a detailed classification of subtypes of major depression, comparing patients with melancholic and non-melancholic major depression. Inpatients suffering from acute major depression were diagnosed and subclassified according to DSM IV criteria. Cell counts were determined by FACS analysis and morphology. Cytokine production (IL-2, IFN-gamma, IL-10) upon mitogen stimulation was measured by ELISA in a whole blood assay. Non-melancholic patients showed increased counts of leukocytes, lymphocytes and NK-cells in the acute stage of disease and after two and four weeks of treatment. Their lymphokine production was unchanged compared to that of healthy controls. Melancholic patients on the other hand demonstrated normal cell counts but a decreased production of IL-2, IFN-gamma and IL-10 during the acute stage of disease followed by a normalization with clinical improvement. Melancholic and non-melancholic patients showed different immune patterns. Classifying melancholic and non-melancholic patients is helpful towards the identification of immune characteristics typical for these diseases.

Adult↗
PubMed2001

Inflammatory markers in major depression and melancholia.

BACKGROUND: There is evidence that patients with major depression (MD) also suffer an inflammatory immune reaction. However, the results remain ambiguous. This could be due to the psychiatrically heterogeneous patient samples investigated in many published studies. Since melancholic depression is psychopathologically and possibly etiologically different from non-melancholic MD, we focused on investigating immune parameters in these two subgroups. METHODS: 43 in-patients suffering from acute major depression were diagnosed, sub-classified according to DSM IV criteria, and compared to 43 matched healthy controls. Cell counts were determined by morphology, and acute phase proteins [c-reactive protein (CRP), alpha(2)-macroglobulin (A2M), haptoglobin (HP)] were measured by laser nephelometry. Cytokine production (IL-1beta) upon mitogen stimulation was measured by ELISA in a whole blood assay. RESULTS: Non-melancholic patients showed increased monocyte counts and A2M serum concentrations in the acute stage of disease and after 2 and 4 weeks of treatment. Melancholic patients demonstrated a decreased monocyte count upon admission and after 4 weeks of treatment. HP levels and IL-1beta production were unchanged in all studied subjects. LIMITATIONS: Medication of the patients varied. The differentiation between melancholic and non-melancholic depression was performed clinically and was not performed using any standardized instrument. CONCLUSION: Melancholic and non-melancholic patients show different immune patterns. This differentiation might clarify immunological findings in MD and point towards etiological factors that are involved in the development of various subtypes of MD.

Acute-Phase Proteins↗
PubMed2001

S-100B is increased in melancholic but not in non-melancholic major depression.

BACKGROUND: Recent evidence suggests that neurodegeneration may be involved in the pathophysiology of major depression. The astroglial peptide S-100B was shown to be increased in many diseases causing neuronal cell damage or degeneration. METHOD: S-100B plasma levels were determined in 28 patients with major depression and 28 matched healthy controls using an immunofluorometric sandwich assay. RESULTS: Patients suffering from melancholic depression showed significantly increased S-100B levels compared to healthy controls while non-melancholic patients demonstrated normal levels. LIMITATIONS: Medication of patients varied. The differentiation between melancholic and non-melancholic patients was performed clinically without using a standardized instrument. CONCLUSIONS: Neurodegeneration or axonal remodeling may be involved in the pathogenesis of melancholic depression.

Adult↗
PubMed2001

Increased S100B blood levels in unmedicated and treated schizophrenic patients are correlated with negative symptomatology.

S100B, a calcium-binding protein produced by astroglial cells, is a marker of astroglial cellular integrity. It has been shown to be increased in acute brain damage and neurodegeneration. A recent study showed increased S100B levels in medicated acutely psychotic patients with schizophrenia. The study presented here included 26 drug-free patients with acute schizophrenia and 26 matched healthy controls. S100B blood concentrations were determined using a quantitative immunoassay upon admission and after 6 weeks of neuroleptic treatment. The PANSS was used to investigate psychopathology. Unmedicated schizophrenic patients showed significantly increased S100B levels compared to matched healthy controls. After 6 weeks of treatment, 11 patients showed normal S100B levels while in 15 patients the levels remained increased. These patients showed significantly higher PANSS negative scores upon admission and after 6 weeks of treatment. Schizophrenic patients display a loss of astroglial integrity which is not caused by neuroleptic medication. Continuously increased S100B levels are associated with negative symptomatology.

Adult↗
PubMed2000

Cytokine production in unmedicated and treated schizophrenic patients.

Recent findings have strengthened the hypothesis that immunological dysfunctions may contribute towards the multifactorial pathogenesis of schizophrenia. The validity of these findings is questioned by the fact that most studied subjects have received potentially immunomodulatory medication upon investigation. In order to rule out such confounding effects, 24 initially unmedicated acutely ill schizophrenic patients were studied immunologically and psychiatrically (PANSS) before and during 4 weeks of neuroleptic treatment. The production of IFN-gamma was decreased upon admission and after 2 weeks of treatment compared to matched healthy controls. No differences in IL-2 and IFN-gamma production between unmedicated and medicated states were observed. These results do not support the notion that neuroleptic medication in vivo might influence TH1 cytokine production in schizophrenia.

Antipsychotic Agents↗
PubMed2000

Decreased in vitro production of interferon-gamma and interleukin-2 in whole blood of patients with schizophrenia during treatment.

A pattern of aberrations in the T-cell cytokine system that is typical for autoimmune disorders has also been reported in patients with schizophrenia, namely a decreased interleukin-2 (IL-2) production and increased levels of the soluble IL-2 receptor (sIL-2R). It has also been reported that the production of interferon-gamma (IFN-gamma) may be lowered. In a longitudinal design, we studied the production of both IFN-gamma and IL-2 and their correlation in patients with schizophrenia during treatment and investigated whether associations exist between cytokine production and clinical variables. The production of IFN-gamma and IL-2 was measured in equal numbers (n = 29) of patients with schizophrenia (DSM-IV) and controls who were matched for age and gender. Patients were measured 1 day after admission (T1), after 14 (T2) and 28 (T2) days of treatment. Psychopathology was assessed after these times. The production of both IFN-gamma and IL-2 was significantly lower in patients than in controls throughout the whole investigation period (T1-T3). The productions of both cytokines were significantly correlated in controls (r = 0.60, P </= 0.001) as well as in patients with schizophrenia (mean production T1-T3: r = 0.71, P </= 0.001). No associations between cytokine measurements and psychopathology or age-at-onset could be found. Our findings of lowered and correlated IFN-gamma and IL-2 production indicate that alterations in the cytokine system of patients with schizophrenia might resemble those in autoimmune disorders. It is suggested that these immunological abnormalities are associated with acute exacerbation, rather than with a clinical subtype of schizophrenia.

Adolescent↗
PubMed1999

Effects of amantadine treatment on in vitro production of interleukin-2 in de-novo patients with idiopathic Parkinson's disease.

An involvement of immunological events in the process of neurodegeneration has frequently been reported. We investigated the cytokine producing capacity for interleukin-2 (IL-2), interferon-gamma (IFN-gamma) and interleukin-10 (IL-10) in whole blood cultures of de-novo patients with idiopathic Parkinson's disease (PD) at the time of first diagnosis and after oral amantadine treatment. Before treatment, productions of IL-2 and IFN-gamma were markedly decreased in PD patients compared to patients with major depressive disorder and healthy controls. After amantadine treatment, the in vitro IL-2 secretion defect was corrected to normal levels in half of the patients, and the increase in IL-2 production was correlated with an increase in IFN-gamma secretion. Our findings suggest that immunological abnormalities occur in the course of PD and that a formerly unappreciated therapeutic potential of amantadine may arise from its immunomodulatory effects on altered T cell function in patients with PD.

Adult↗
PubMed1999

Elevated plasma levels of S-100b protein in schizophrenic patients.

BACKGROUND: In this study, we examined the possibility that structural damage to the brain may play a role in the pathogenesis of schizophrenia. METHODS: We compared plasma levels of S-100b protein in 20 patients with schizophrenic psychosis and 20 age- and gender-matched healthy blood donors. Concentrations of S-100 protein were determined by microtiter-based immunofluorometric assay detecting predominantly S-100b. RESULTS: Mean concentrations of S-100b protein in blood were significantly (p < or = .001) higher in schizophrenic patients (0.165 +/- 0.138 microgram/L) compared to control subjects (0.054 +/- 0.031 microgram/L). Levels did not correlate with age of onset or duration of psychosis. CONCLUSIONS: Our findings indicate that patients with schizophrenia may suffer ongoing structural damage to cells of the central nervous system, and that the concentration of S-100b protein in plasma may help to identify clinical subgroups in schizophrenia.

Adult↗
PubMed1998

Increased serum neopterin levels in acutely ill and recovered schizophrenic patients.

Twenty-nine in-patients with acute schizophrenia were examined to assess serum neopterin levels by ELISA at two points of time: during the state of acute symptoms and after clinical recovery at the point of discharge (at an interval of 30.84 +/- 15.22 days). Patients showed significantly higher levels of neopterin than controls. Moreover, the neopterin levels were significantly higher in patients after clinical improvement than in acutely ill patients. Neopterin levels in patients after clinical recovery were negatively correlated to scores of psychopathological symptoms, and positively to neuroleptic medication at the acute stage of the disease. The increase of serum neopterin during treatment of schizophrenia may reflect an up-regulation of dopamine turnover, rather than immunological activity.

Acute Disease↗
PubMed1998

Immunological dysfunction in schizophrenia: a systematic approach.

BACKGROUND: In the present study, immunological alterations were investigated as one possible factor contributing towards the pathogenesis of schizophrenia. Specifically cellular changes, deviating cytokine production and interfering variables were studied in order to improve our understanding of how these factors interact. METHOD: 44 acutely ill schizophrenics were compared with matched healthy controls. Cell numbers were determined by flow cytometry and cytokine production by whole blood assay and ELISA. A criss-cross technique was employed for the assessment of interfering serum factors. RESULTS: Cell counts for leukocytes, lymphocytes, pan T cells, activated T cells and the absolute B cell count of the schizophrenic patients were all within normal limits. The absolute and relative monocyte counts, the number of IL-2 receptor carrying T cells and the relative B cell count were slightly elevated. IL-2 and IFN-gamma production were increased while IL-10 production, the sIL-2R and cortisol levels remained unchanged. No interfering serum factors were detected. CONCLUSION: The deficient production of TH-1 cytokines in schizophrenia is not due either to a changed number of immunocompetent cells or to a counterregulation of the TH-2 cytokine IL-10. Serum factors in in vitro testing are not responsible for the deficient cytokine production.

Acute Disease↗