title: Monocyte and microglial activation in patients with mood-stabilized bipolar disorder.
abstract: 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.
  
  
  CONCLUSIONS
  The cross-sectional study design precludes conclusions about causality.
  
  
  CONCLUSIONS
  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.
authors.affiliation: The Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Joel
authors.initials: J
authors.lastname: Jakobsson
authors.affiliation: The Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Bjerke
authors.affiliation: The Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Sara
authors.initials: S
authors.lastname: Sahebi
authors.affiliation: The Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Anniella
authors.initials: A
authors.lastname: Isgren
authors.affiliation: The Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Carl Johan
authors.initials: CJ
authors.lastname: Ekman
authors.affiliation: The Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Carl
authors.initials: C
authors.lastname: Sellgren
authors.affiliation: The Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Bob
authors.initials: B
authors.lastname: Olsson
authors.affiliation: 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.
authors.forename: Henrik
authors.initials: H
authors.lastname: Zetterberg
authors.affiliation: The Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Kaj
authors.initials: K
authors.lastname: Blennow
authors.affiliation: The Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Erik
authors.initials: E
authors.lastname: Pålsson
authors.affiliation: 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.
authors.forename: Mikael
authors.initials: M
authors.lastname: Landén
mesh_terms: D054392:Adipokines / Q000097:blood / Q000134:cerebrospinal fluid; D000328:Adult; D015415:Biomarkers / Q000097:blood / Q000134:cerebrospinal fluid; D001714:Bipolar Disorder / Q000097:blood / Q000134:cerebrospinal fluid / Q000188:drug therapy / Q000276:immunology*; D018932:Chemokine CCL2 / Q000097:blood / Q000134:cerebrospinal fluid; D000071451:Chitinase-3-Like Protein 1; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D037102:Lectins / Q000097:blood / Q000134:cerebrospinal fluid; D018950:Lipopolysaccharide Receptors / Q000097:blood / Q000134:cerebrospinal fluid; D008297:Male; D017628:Microglia / Q000276:immunology*; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology*; D011619:Psychotropic Drugs / Q000627:therapeutic use; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood / Q000134:cerebrospinal fluid; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000097:blood / Q000134:cerebrospinal fluid
chemical_list: D054392:Adipokines; D015415:Biomarkers; C111835:CCL2 protein, human; C084533:CHI3L1 protein, human; D018932:Chemokine CCL2; D000071451:Chitinase-3-Like Protein 1; D037102:Lectins; D018950:Lipopolysaccharide Receptors; D011619:Psychotropic Drugs; C560822:TIMP1 protein, human; C560823:TIMP2 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2