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      Neuropsychiatric Disease and Treatment (submit here)

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      Mean platelet volume in bipolar disorder: the search for an ideal biomarker

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          Abstract

          Background

          The pathophysiology of bipolar disorder (BD) remains a mystery. In this context, interest in the role of the immune and inflammatory systems in BD has been increasing. We aimed to compare the routine hemogram values of BD patients with those of the participants in the healthy control group, to assess the inflammation levels of the two groups. Mean platelet volume (MPV) can be obtained as routine hemogram parameters and may aid in the detection of systemic inflammation.

          Subjects and methods

          This study was conducted with BD (manic episode) inpatients (n=132) and healthy controls (n=135). Abnormally distributed variables (ie, neutrophil–lymphocyte ratio [NLR], platelet–lymphocyte ratio [PLR], neutrophils, lymphocytes, hemoglobin, hematocrit [HCT], mean corpuscular volume [MCV], mean corpuscular hemoglobin [MCH], mean corpuscular hemoglobin concentration [MCHC], red cell distribution width [RDW], MPV, and plateletcrit [PCT]) were compared using the Mann–Whitney U-test. Student’s t-test was used to compare the mean ages and white blood cell, red blood cell, and platelet counts of the patients with BD against those of the participants in the control group.

          Results

          The comparisons revealed that while the mean WBC and the median NLR, PLR, neutrophil, lymphocyte, MPV, and PCT values were significantly higher in the patients with BD ( P<0.05), the median hemoglobin, RBC, HCT, and MCHC values were significantly higher in the control group ( P<0.05).

          Conclusion

          Comparisons of hemogram values of patients with BD against those of the healthy control group revealed that inflammatory cells (absolute neutrophil count, platelet count, PCT, and MPV) and ratios (NLR, PLR) seem to be altered during manic episodes. These findings support the hypothesis that inflammatory activation occurs in BD during manic episodes. In addition to NLR and PLR, MPV may be useful in the detection of this activation. The most significant limitation in the study is that smokers were not excluded in both groups. The development of new preventive and therapeutic options can be facilitated through the understanding of this mechanism because through this mechanism, inflammation may pathologically affect brain function, as well as inducing and/or perpetuating BD.

          Most cited references33

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          Neuroinflammation and psychiatric illness

          Multiple lines of evidence support the pathogenic role of neuroinflammation in psychiatric illness. While systemic autoimmune diseases are well-documented causes of neuropsychiatric disorders, synaptic autoimmune encephalitides with psychotic symptoms often go under-recognized. Parallel to the link between psychiatric symptoms and autoimmunity in autoimmune diseases, neuroimmunological abnormalities occur in classical psychiatric disorders (for example, major depressive, bipolar, schizophrenia, and obsessive-compulsive disorders). Investigations into the pathophysiology of these conditions traditionally stressed dysregulation of the glutamatergic and monoaminergic systems, but the mechanisms causing these neurotransmitter abnormalities remained elusive. We review the link between autoimmunity and neuropsychiatric disorders, and the human and experimental evidence supporting the pathogenic role of neuroinflammation in selected classical psychiatric disorders. Understanding how psychosocial, genetic, immunological and neurotransmitter systems interact can reveal pathogenic clues and help target new preventive and symptomatic therapies.
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            Inflamed moods: a review of the interactions between inflammation and mood disorders.

            Mood disorders have been recognized by the World Health Organization (WHO) as the leading cause of disability worldwide. Notwithstanding the established efficacy of conventional mood agents, many treated individuals continue to remain treatment refractory and/or exhibit clinically significant residual symptoms, cognitive dysfunction, and psychosocial impairment. Therefore, a priority research and clinical agenda is to identify pathophysiological mechanisms subserving mood disorders to improve therapeutic efficacy. During the past decade, inflammation has been revisited as an important etiologic factor of mood disorders. Therefore, the purpose of this synthetic review is threefold: 1) to review the evidence for an association between inflammation and mood disorders, 2) to discuss potential pathophysiologic mechanisms that may explain this association and 3) to present novel therapeutic options currently being investigated that target the inflammatory-mood pathway. Accumulating evidence implicates inflammation as a critical mediator in the pathophysiology of mood disorders. Indeed, elevated levels of pro-inflammatory cytokines have been repeatedly demonstrated in both major depressive disorder (MDD) and bipolar disorder (BD) patients. Further, the induction of a pro-inflammatory state in healthy or medically ill subjects induces 'sickness behavior' resembling depressive symptomatology. Potential mechanisms involved include, but are not limited to, direct effects of pro-inflammatory cytokines on monoamine levels, dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, pathologic microglial cell activation, impaired neuroplasticity and structural and functional brain changes. Anti-inflammatory agents, such as acetyl-salicylic acid (ASA), celecoxib, anti-TNF-α agents, minocycline, curcumin and omega-3 fatty acids, are being investigated for use in mood disorders. Current evidence shows improved outcomes in mood disorder patients when anti-inflammatory agents are used as an adjunct to conventional therapy; however, further research is needed to establish the therapeutic benefit and appropriate dosage. Copyright © 2014 Elsevier Inc. All rights reserved.
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              Imbalance between pro-inflammatory and anti-inflammatory cytokines in bipolar disorder.

              The role of cytokines in bipolar disorder is still controversial. Although a few studies have found alterations of cytokines in bipolar disorder, their findings were inconsistent. The aim of this study was to determine whether the cytokines are involved in the pathophysiology of bipolar disorder. A total of 37 manic patients with bipolar disorder and 74 control subjects were recruited. The mitogen-induced production of tumor necrosis factor (TNF)-alpha, interleukin-6 (IL-6), IL-4, interferon (IFN)-gamma, and IL-2 was measured using quantitative sandwich ELISA at the time of admission and 6 weeks after mood stabilizer treatment. IL-6 and TNF-alpha production of bipolar manic patients was significantly higher than those of normal controls, while IL-4 values of the patients were significantly lower than normal controls. IL-6/IL-4, TNF-alpha/IL-4, IL-2/IL-4, and IFN-gamma/IL-4 ratios were significantly higher in bipolar manic patients than in normal controls. After 6 weeks of treatment, the levels of IL-6 significantly decreased compared with baseline. The effect of various types of mood stabilizers on cytokine production should be considered. These findings suggest that the increased activity of pro-inflammatory cytokines and an imbalance between pro-inflammatory and anti-inflammatory cytokines may play a role in the pathophysiology of bipolar disorder.
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                Author and article information

                Journal
                Neuropsychiatr Dis Treat
                Neuropsychiatr Dis Treat
                Neuropsychiatric Disease and Treatment
                Neuropsychiatric Disease and Treatment
                Dove Medical Press
                1176-6328
                1178-2021
                2016
                16 August 2016
                : 12
                : 2057-2062
                Affiliations
                [1 ]Department of Psychiatry
                [2 ]Department of Hematology, Faculty of Medicine, Cumhuriyet University, Sivas, Turkey
                Author notes
                Correspondence: Derya Guliz Mert, Department of Psychiatry, Faculty of Medicine, Cumhuriyet University, 58140 Sivas, Turkey, Tel +90 346 258 0000, Email drgulizaksoy@ 123456yahoo.com
                Article
                ndt-12-2057
                10.2147/NDT.S112374
                4998027
                27578978
                2d9eb76b-a80a-492d-b48a-1c5a6fe6ff85
                © 2016 Mert and Terzi. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                History
                Categories
                Original Research

                Neurology
                bipolar disorder,inflammation,mean platelet volume
                Neurology
                bipolar disorder, inflammation, mean platelet volume

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