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        Depression and Mania Induce Pro-inflammatory Activation of Macrophages Following Application of Serum from Individuals with Bipolar Disorder

        Pamela Ferrari,Mariana Migliorini Parisi,Rafael Colombo,Matheus Becker,Gabriel Fries,Bruna Maria Ascoli,Luiza Paul Géa,Márcia Kauer-Sant’anna,Flávio Kapczinski,Fábio Klamt,Fátima T.C.R. Guma,Adriane R 대한정신약물학회 2018 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.16 No.1

        Objective: Evidence has suggested that immune imbalance is involved with bipolar disorder (BD); however, its precise mechanism is poorly understood. This study investigated whether biochemical changes in the serum from BD patients could modulate the phenotype of cultured macrophages. Methods: Eighteen subjects with BD and five healthy individuals were included in this study. The human monocyte cell line U-937 was activated with phorbol 12-myristate 13-acetate (PMA) and polarization was induced with RPMI-1640 media supplemented with 10% serum from each patient for 24 hours. Gene expression of selected M1 and M2 markers was assessed by quantitative PCR. Results: Macrophages exposed to serum of manic and depressive BD patients displayed an increase of interleukin-1 (6.40±3.47 and 9.04±5.84 vs. 0.23±0.11; p<0.05) and tumor necrosis factor- (2.23±0.91 and 2.03±0.45 vs. 0.62±0.24; p=0.002 and p=0.004, respectively) compared to euthymic group (there was no difference between euthymic and controls). In parallel, U-937 macrophages treated with serum of patients in acute episode displayed a down-regulation of CXCL9 (0.29±0.20 vs. 1.86±1.61; p=0.006) and CXCL10 expression (0.36±0.15 and 0.86±0.24 vs. 1.83±0.88; p<0.000 and p=0.04) compared to the euthymia group. Conclusion: Our results are consistent with previous studies showing that changes in peripheral blood markers could modulate M1/M2 polarization in BD. The evidence of macrophages as source of inflammatory cytokines might be helpful to unravel how the mononuclear phagocyte system is involved in the etiology of BD.

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        Potential Candidates for Biomarkers in Bipolar Disorder: A Proteomic Approach through Systems Biology

        Paola Rampelotto Ziani,Jacson Gabriel Feiten,Jé,ferson Ferraz Goularte,Rafael Colombo,Bá,rbara Antqueviezc,Luiza Paul Gé,a,Adriane Ribeiro Rosa 대한정신약물학회 2022 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.20 No.2

        Bipolar disorder (BD) is one of the most disabling diseases characterized by severe humor fluctuation. It is accompanied by cognitive and functional impairment in addiction to high suicide rates. BD is often underdiagnosed and treated incorrectly because many of the reported symptoms are not exclusive to the disorder. Once the diagnosis is exclusively clinical, it is not possible to state precisely. From that, proteomic approaches were used to identify, in a large scale, all proteins involved in cellular or tissue processes. This review aggregate data from blood proteomes, by using protein association network, of subjects with BD and healthy controls to suggest dysfunctional molecular pathways involved in disease. Original articles containing proteomic analysis were searched in PubMed. Seven studies were selected and data were extracted for posterior analysis. A protein-protein interaction network was created by STRING database. A final set of proteins in this network were employed as input in ClueGO and, the main biological process was visualized using R package pathview. The analysis revealed proteins associated with many biological processes, including growth and endocrine regulation, iron transportation, protease inhibition, protection against pathogens and cholesterol transport. Moreover, pathway analysis indicated the association of uncovered proteins with two main metabolic pathways: complement system and coagulation cascade. Thus, a better understanding on the pathophysiology of psychiatric disorders and the identification of potential biomarker candidates are essential to improve diagnostic, prognostic and design pharmacological strategies.

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