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      The Historical Development of Immunoendocrine Concepts of Psychiatric Disorders and Their Therapy

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          Abstract

          Relationships between the central nervous, immune and endocrine systems are a focus of psychiatric research, particularly in depression and schizophrenia. The field has long antecedents. Observed phenomena attributable to these relationships date back to the Neolithic era. Immunoendocrine theories in the broadest sense are recorded in antiquity. In the 19th century, Kraepelin and Wagner-Jauregg reported pioneering clinical observations in psychiatric patients. Von Basedow, Addison and Cushing described psychiatric symptoms in patients suffering from endocrine diseases. The 20th century opened with the identification of hormones, the first, adrenaline, chemically isolated independently by Aldrich und Takamine in 1901. Berson and Yalow developed the radioimmunoassay (RIA) technique in 1959 making it possible to measure levels of hormones and cytokines. These developments have enabled great strides in psychoimmunoendocrinology. Contemporary research is investigating diagnostic and therapeutic applications of these concepts, for example by identifying biomarkers within the endocrine and immune systems and by synthesizing and testing drugs that modulate these systems and show antidepressant or antipsychotic properties.

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          Most cited references151

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          An endotoxin-induced serum factor that causes necrosis of tumors.

          In studying "hemorrhagic necrosis" of tumors produced by endotoxin, it was found that the serum of bacillus Calmette--Guerin (BCG)-infected mice treated with endotoxin contains a substance (tumor necrosis factor; TNF) which mimics the tumor necrotic action of endotoxin itself. TNF-positive serum is as effective as endotoxin itself in causing necrosis of the sarcoma Meth A and other transplanted tumors. A variety of tests indicate that TNF is not residual endotoxin, but a factor released from host cells, probably macrophages, by endotoxin. Corynebacteria and Zymosan, which like BCG induce hyperplasia of the reticulo-endothelial system, can substitute for BCG in priming mice for release of TNF by endotoxin. TNF is toxic in vitro for two neoplastic cell lines; it is not toxic for mouse embryo cultures. We propose that TNF mediates endotoxin-induced tumor necrosis, and that it may be responsible for the suppression of transformed cells by activated macrophages.
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            The cyclooxygenase-2 inhibitor celecoxib has therapeutic effects in major depression: results of a double-blind, randomized, placebo controlled, add-on pilot study to reboxetine.

            Signs of an inflammatory process, in particular increased pro-inflammatory cytokines and increased levels of prostaglandine E(2) (PGE(2)), have repeatedly been described in major depression (MD). As cyclooxygenase-2 (COX-2) inhibitors inhibit the PGE(2) production and the production of pro-inflammatory cytokines, we performed a therapeutic trial with the COX-2 inhibitor celecoxib. In a prospective, double-blind, add-on study, 40 patients suffering from an acute depressive episode were randomly assigned to either reboxetine and celecoxib or to reboxetine plus placebo. After a wash-out period, 20 patients received 4-10 mg reboxetine plus placebo and 20 received reboxetine plus 400 mg celecoxib for 6 weeks. The treatment effect was calculated by analysis of variance. There were no significant differences between groups in age, sex, duration or severity of disease or psychopathology, or reboxetine dose or plasma levels. Over 6 weeks, both groups of patients showed significant improvement in scores of the Hamilton Depression Scale. However, the celecoxib group showed significantly greater improvement compared to the reboxetine-alone group. Additional treatment with celecoxib has significant positive effects on the therapeutic action of reboxetine with regard to depressive symptomatology. Moreover, the fact that treatment with an anti-inflammatory drug showed beneficial effects on MD indicates that inflammation is related to the pathomechanism of the disorder, although the exact mechanisms remain to become elucidated.
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              The mechanism of pancreatic secretion.

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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                04 December 2015
                December 2015
                : 16
                : 12
                : 28841-28869
                Affiliations
                [1 ]Archives for the History of Psychiatry in Leipzig, Department of Psychiatry, University of Leipzig, Leipzig 04103, Germany
                [2 ]Department of Mental Health, University of Tasmania, Hobart TAS 7005, Australia; ken.kirkby@ 123456utas.edu.au
                [3 ]Department of Psychiatry, University of Leipzig, Leipzig 04103, Germany
                [4 ]Department of Psychological Medicine, King’s College London, London SE5 8AF, UK; hubertus.himmerich@ 123456kcl.ac.uk
                Author notes
                [* ]Correspondence: holger.steinberg@ 123456medizin.uni-leipzig.de ; Tel.: +49-341-972-4113; Fax: +49-341-972-4559
                Article
                ijms-16-26136
                10.3390/ijms161226136
                4691083
                26690116
                78958234-875d-4ff7-9e37-e395a8afe329
                © 2015 by the authors; licensee MDPI, Basel, Switzerland.

                This article is an open access article distributed under the terms and conditions of the Creative Commons by Attribution (CC-BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 09 October 2015
                : 24 November 2015
                Categories
                Review

                Molecular biology
                immune system,cytokines,hormones,depression,schizophrenia,history of psychiatry
                Molecular biology
                immune system, cytokines, hormones, depression, schizophrenia, history of psychiatry

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