Bipolar disorder (BD) is a chronic affective disorder with extreme mood swings that include mania or hypomania and depression. Though the exact mechanism of BD is unknown, neuroinflammation is one of the numerous investigated etiopathophysiological causes of BD. This article presents a systematic review of the data regarding brain inflammation evaluating microglia, astrocytes, cytokines, chemokines, adhesion molecules, and other inflammatory markers in postmortem BD brain samples. This systematic review was performed according to PRISMA recommendations, and relevant studies were identified by searching the PubMed/MEDLINE, PsycINFO, EMBASE, LILACS, IBECS, and Web of Science databases for peer-reviewed journal articles published by March 2019. Quality of included studies appraised using the QUADAS-2 tool. Among the 1814 articles included in the primary screening, 51 articles measured inflammatory markers in postmortem BD brain samples. A number of studies have shown evidence of inflammation in BD postmortem brain samples. However, an absolute statement cannot be concluded whether neuroinflammation is present in BD due to the large number of studies did not evaluate the presence of infiltrating peripheral immune cells in the central nervous system (CNS) parenchyma, cytokines levels, and microglia activation in the same postmortem brain sample. For example, out of 15 studies that evaluated microglia cells markers, 8 studies found no effect of BD on these cells. Similarly, 17 out of 51 studies evaluating astrocytes markers, 9 studies did not find any effect of BD on astrocyte cells, whereas 8 studies found a decrease and 2 studies presented both increase and decrease in different brain regions. In addition, multiple factors account for the variability across the studies, including postmortem interval, brain area studied, age at diagnosis, undergoing treatment, and others. Future analyses should rectify these potential sources of heterogeneity and reach a consensus regarding the inflammatory markers in postmortem BD brain samples.
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Cerebrospinal fluid proteomic study of two bipolar disorder cohorts
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The Translational Psychiatry Program (USA) is funded by the Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth). The Laboratory of Neurosciences (Brazil) is one of the centers of the National Institute for Molecular Medicine (INCT-MM) and one of the members of the Centre of Excellence in Applied Neurosciences of Santa Catarina (NENASC). Its research is supported by grants from the National Council for Scientific and Technological Development (CNPq) (JQ and TB), the Foundation for Research and Innovation of the State of Santa Catarina (FAPESC) (JQ and TB), and the InstitutoCérebro e Mente (JQ) and UNESC (JQ and TB).
Conflict of interest
JQ: Clinical Research Support: Allergan (Clinical Trial), Janssen Pharmaceuticals, Inc. (Clinical Trial). Advisory Boards, Speaker Bureaus, Expert Witness, or Consultant. Assurex Health, Inc. (Speaker Bureau), Daiichi Sankyo (Speaker Bureau), Janssen Pharmaceuticals, Inc. (Speaker Bureau). Patent, Equity, or Royalty: Instituto de Neurociencias. Dr. Joao Quevedo (Stockholder), Other Artmed Editora (Copyright), Artmed Panamericana (Copyright), Elsevier (Copyright). The other authors declare that they have no conflict of interest.
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Giridharan, V.V., Sayana, P., Pinjari, O.F. et al. Postmortem evidence of brain inflammatory markers in bipolar disorder: a systematic review. Mol Psychiatry 25, 94–113 (2020). https://doi.org/10.1038/s41380-019-0448-7
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