PMID- 25768030 OWN - NLM STAT- MEDLINE DCOM- 20161109 LR - 20191113 IS - 1488-2434 (Electronic) IS - 1180-4882 (Print) IS - 1180-4882 (Linking) VI - 40 IP - 4 DP - 2015 Jul TI - Monocyte and microglial activation in patients with mood-stabilized bipolar disorder. PG - 250-8 AB - BACKGROUND: Bipolar disorder is associated with medical comorbidities that have been linked to systemic inflammatory mechanisms. There is, however, limited evidence supporting a role of neuroinflammation in bipolar disorder. Here we tested whether microglial activation and associated tissue remodelling processes are related to bipolar disorder by analyzing markers in cerebrospinal fluid (CSF) and serum from patients and healthy controls. METHODS: Serum was sampled from euthymic patients with bipolar disorder and healthy controls, and CSF was sampled from a large subset of these individuals. The levels of monocyte chemoattractant protein-1 (MCP-1), YKL-40, soluble cluster of differentiation 14 (sCD14), tissue inhibitor of metalloproteinases-1 (TIMP-1) and tissue inhibitor of metalloproteinases-2 (TIMP-2), were measured, and we adjusted comparisons between patients and controls for confounding factors. RESULTS: We obtained serum samples from 221 patients and 112 controls and CSF samples from 125 patients and 87 controls. We found increased CSF levels of MCP-1 and YKL-40 and increased serum levels of sCD14 and YKL-40 in patients compared with controls; these differences remained after controlling for confounding factors, such as age, sex, smoking, blood-CSF barrier function, acute-phase proteins and body mass index. The CSF levels of MCP-1 and YKL-40 correlated with the serum levels, whereas the differences between patients and controls in CSF levels of MCP-1 and YKL-40 were independent of serum levels. LIMITATIONS: The cross-sectional study design precludes conclusions about causality. CONCLUSION: Our results suggest that both neuroinflammatory and systemic inflammatory processes are involved in the pathophysiology of bipolar disorder. Importantly, markers of immunological processes in the brain were independent of peripheral immunological activity. FAU - Jakobsson, Joel AU - Jakobsson J AD - The Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. FAU - Bjerke, Maria AU - Bjerke M AD - The Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. FAU - Sahebi, Sara AU - Sahebi S AD - The Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. FAU - Isgren, Anniella AU - Isgren A AD - The Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. FAU - Ekman, Carl Johan AU - Ekman CJ AD - The Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden. FAU - Sellgren, Carl AU - Sellgren C AD - The Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. FAU - Olsson, Bob AU - Olsson B AD - The Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. FAU - Zetterberg, Henrik AU - Zetterberg H AD - The Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; and UCL Institute of Neurology, Queen Square, London, UK. FAU - Blennow, Kaj AU - Blennow K AD - The Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. FAU - Palsson, Erik AU - Palsson E AD - The Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. FAU - Landen, Mikael AU - Landen M AD - The Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; and the Departments of Clinical Neuroscience and Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Canada TA - J Psychiatry Neurosci JT - Journal of psychiatry & neuroscience : JPN JID - 9107859 RN - 0 (Adipokines) RN - 0 (Biomarkers) RN - 0 (CCL2 protein, human) RN - 0 (CHI3L1 protein, human) RN - 0 (Chemokine CCL2) RN - 0 (Chitinase-3-Like Protein 1) RN - 0 (Lectins) RN - 0 (Lipopolysaccharide Receptors) RN - 0 (Psychotropic Drugs) RN - 0 (TIMP1 protein, human) RN - 0 (TIMP2 protein, human) RN - 0 (Tissue Inhibitor of Metalloproteinase-1) RN - 127497-59-0 (Tissue Inhibitor of Metalloproteinase-2) SB - IM MH - Adipokines/blood/cerebrospinal fluid MH - Adult MH - Biomarkers/blood/cerebrospinal fluid MH - Bipolar Disorder/blood/cerebrospinal fluid/drug therapy/*immunology MH - Chemokine CCL2/blood/cerebrospinal fluid MH - Chitinase-3-Like Protein 1 MH - Cross-Sectional Studies MH - Female MH - Humans MH - Lectins/blood/cerebrospinal fluid MH - Lipopolysaccharide Receptors/blood/cerebrospinal fluid MH - Male MH - Microglia/*immunology MH - Middle Aged MH - Monocytes/*immunology MH - Psychotropic Drugs/therapeutic use MH - Tissue Inhibitor of Metalloproteinase-1/blood/cerebrospinal fluid MH - Tissue Inhibitor of Metalloproteinase-2/blood/cerebrospinal fluid PMC - PMC4478058 EDAT- 2015/03/15 06:00 MHDA- 2016/11/10 06:00 PMCR- 2015/07/01 CRDT- 2015/03/14 06:00 PHST- 2015/03/14 06:00 [entrez] PHST- 2015/03/15 06:00 [pubmed] PHST- 2016/11/10 06:00 [medline] PHST- 2015/07/01 00:00 [pmc-release] AID - 10.1503/jpn.140183 [pii] AID - jpn-40-250 [pii] AID - 10.1503/jpn.140183 [doi] PST - ppublish SO - J Psychiatry Neurosci. 2015 Jul;40(4):250-8. doi: 10.1503/jpn.140183.