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      Neuropsychiatric Disease and Treatment (submit here)

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      Associations of Serum Cytokines, Growth Factors, and High-Sensitivity C-Reactive Protein Levels in Patients with Major Depression with and without Type 2 Diabetes Mellitus: An Explanatory Investigation

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          Abstract

          Purpose

          We investigated the serum levels of cytokines, including interleukin 1β (IL-β), IL-6, IL-8, IL-10, tumor necrosis factor-alpha (TNF-α), and growth factors, including brain-derived neurotrophic factor, vascular endothelial growth factor, and insulin-like growth factor 1, and their association with major depression in patients with and without type 2 diabetes mellitus. We also investigated the response to antidepressant treatment in both groups.

          Patients and Methods

          Forty-one patients with major depression were recruited at the University Hospital of Occupational and Environmental Health. All patients were diagnosed with major depression using the Diagnostic and Statistical Manual for Mental Disorders, Fifth Edition. Type 2 diabetes mellitus was diagnosed according to the criteria of the Japan Diabetes Society. Six healthy controls with no history of psychiatric or physical diseases were also enrolled. Serum levels of several cytokines, growth factors, and high-sensitivity C-reactive protein (hs-CRP) were measured. The clinical symptoms of patients with major depression were assessed using the Montgomery-Asberg Depression Rating Scale.

          Results

          Significant differences in cytokines, growth factors, and hs-CRP were observed between the major depression and healthy control groups. Serum TNF-α levels were significantly higher in patients with major depression and type 2 diabetes mellitus than in those without type 2 diabetes mellitus. In the major depression group, serum IL-6 and hs-CRP levels tended to be higher in patients with type 2 diabetes mellitus than in those without. Several correlations among cytokines, growth factors, and hs-CRP were observed in patients with major depression with and without type 2 diabetes mellitus. Responses to pharmacological interventions for major depression did not differ between patients with and without type 2 diabetes mellitus.

          Conclusion

          Serum levels of TNF-α, hs-CRP, and IL-6 were different between patients with major depression with and without type 2 diabetes mellitus. Also, correlations were found between serum levels of cytokines, growth factors, and hs-CRP in patients with major depression. Inflammatory factors, which may be associated with growth factors, may be involved in the pathophysiology of major depression, particularly among patients with comorbid type 2 diabetes mellitus.

          Most cited references51

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          Diagnostic and Statistical Manual of Mental Disorders

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            Investigation of the freely available easy-to-use software ‘EZR' for medical statistics

            Y Kanda (2012)
            Although there are many commercially available statistical software packages, only a few implement a competing risk analysis or a proportional hazards regression model with time-dependent covariates, which are necessary in studies on hematopoietic SCT. In addition, most packages are not clinician friendly, as they require that commands be written based on statistical languages. This report describes the statistical software ‘EZR' (Easy R), which is based on R and R commander. EZR enables the application of statistical functions that are frequently used in clinical studies, such as survival analyses, including competing risk analyses and the use of time-dependent covariates, receiver operating characteristics analyses, meta-analyses, sample size calculation and so on, by point-and-click access. EZR is freely available on our website (http://www.jichi.ac.jp/saitama-sct/SaitamaHP.files/statmed.html) and runs on both Windows (Microsoft Corporation, USA) and Mac OS X (Apple, USA). This report provides instructions for the installation and operation of EZR.
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              A new depression scale designed to be sensitive to change

              The construction of a depression rating scale designed to be particularly sensitive to treatment effects is described. Ratings of 54 English and 52 Swedish patients on a 65 item comprehensive psychopathology scale were used to identify the 17 most commonly occurring symptoms in primary depressive illness in the combined sample. Ratings on these 17 items for 64 patients participating in studies of four different antidepressant drugs were used to create a depression scale consisting of the 10 items which showed the largest changes with treatment and the highest correlation to overall change. The inner-rater reliability of the new depression scale was high. Scores on the scale correlated significantly with scores on a standard rating scale for depression, the Hamilton Rating Scale (HRS), indicating its validity as a general severity estimate. Its capacity to differentiate between responders and non-responders to antidepressant treatment was better than the HRS, indicating greater sensitivity to change. The practical and ethical implications in terms of smaller sample sizes in clinical trials are discussed.
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                Author and article information

                Journal
                Neuropsychiatr Dis Treat
                Neuropsychiatr Dis Treat
                ndt
                Neuropsychiatric Disease and Treatment
                Dove
                1176-6328
                1178-2021
                03 February 2022
                2022
                : 18
                : 173-186
                Affiliations
                [1 ]Department of Psychiatry, University of Occupational and Environmental Health , Kitakyushu, Fukuoka, 8078555, Japan
                [2 ]3rd Internal Medicine, University of Occupational and Environmental Health , Kitakyushu, Fukuoka, 8078555, Japan
                Author notes
                Correspondence: Reiji Yoshimura, Department of Psychiatry, University of Occupational and Environmental Health , Kitakyushu, Fukuoka, 8078555, Japan, Tel +81936917253, Fax +81936924894, Email yoshi621@med.uoeh-u.ac.jp
                Author information
                http://orcid.org/0000-0003-2791-8113
                http://orcid.org/0000-0001-8328-4608
                Article
                350121
                10.2147/NDT.S350121
                8820450
                35140467
                08bfc4b1-1d40-484f-8c63-309f7566c054
                © 2022 Hoshikawa et al.

                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. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                : 19 November 2021
                : 04 January 2022
                Page count
                Figures: 2, Tables: 20, References: 51, Pages: 14
                Funding
                Funded by: the Institute of Health, Labor, and Welfare in Japan to RY;
                This work was supported in part by grants from the Institute of Health, Labor, and Welfare in Japan to RY (18K07576).
                Categories
                Original Research

                Neurology
                major depression,diabetes mellitus,cytokine,growth factor,high-sensitivity c-reactive protein,brain-derived neurotrophic factor

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