title: Extracellular matrix proteins matrix metallopeptidase 9 (MMP9) and soluble intercellular adhesion molecule 1 (sICAM-1) and correlations with clinical staging in euthymic bipolar disorder.
abstract: OBJECTIVE
  Matrix metallopeptidase 9 (MMP9) and soluble intercellular adhesion molecule 1 (sICAM-1) are both involved in the restructuring of connective tissues. Evidence also implicates MMP9 and sICAM in cardiovascular and neoplastic diseases, where blood levels may be a marker of disease severity or prognosis. In individuals with bipolar disorder (BD), higher risk for cardiovascular illness has been extensively reported.
  
  
  METHODS
  The aim of this investigation was to measure and compare peripheral levels of serum MMP9 and sICAM in adults with euthymic BD and healthy controls (HC). Furthermore, we focussed on correlations with illness severity and metabolic parameters.
  
  
  RESULTS
  MMP9 levels among the BD sample (n = 112) were significantly higher than among the HC (n = 80) (MMP9: F = 9.885, p = 0.002, η(2)  = 0.058) after controlling for confounding factors. Patients with BD in a later, progressive stage of disease showed significantly higher MMP9 as well as sICAM-1 levels compared to patients with BD in an earlier stage of disease (MMP9: F = 5.8, p = 0.018, η(2)  = 0.054; sICAM-1: F = 5.6, p = 0.020, η(2)  = 0.052). Correlation analyses of cognitive measures revealed a negative association between performance on the d2 Test of Attention and MMP9 (r = -0.287, p = 0.018) in the BD sample. Despite the sample being euthymic (i.e., according to conventional criteria) at the time of analysis, we found significant correlations between MMP9 as well as sICAM-1 and subthreshold depressive/hypomanic symptoms.
  
  
  CONCLUSIONS
  A collection of disparate findings herein point to a role of MMP9 and cICAM-1 in the patho-progressive process of BD: the increased levels of serum MMP9 and sICAM-1, the correlation between higher levels of these parameters, progressive stage, and cognitive dysfunction in BD, and the positive correlation with subthreshold symptoms. As sICAM-1 and MMP9 are reliable biomarkers of inflammatory and early atherosclerotic disease, these markers may provide indications of the presence of occult cardiovascular disease in this highly at-risk population.
authors.affiliation: Department of Psychiatry, Medical University of Graz, Graz, Austria.
authors.forename: Eva Z
authors.initials: EZ
authors.lastname: Reininghaus
authors.affiliation: Department of Psychiatry, Medical University of Graz, Graz, Austria.
authors.forename: Nina
authors.initials: N
authors.lastname: Lackner
authors.affiliation: Department of Psychiatry, Medical University of Graz, Graz, Austria.
authors.forename: Armin
authors.initials: A
authors.lastname: Birner
authors.affiliation: Department of Psychiatry, Medical University of Graz, Graz, Austria.
authors.forename: Susanne
authors.initials: S
authors.lastname: Bengesser
authors.affiliation: Department of Psychiatry, Medical University of Graz, Graz, Austria.
authors.forename: Frederike T
authors.initials: FT
authors.lastname: Fellendorf
authors.affiliation: Department of Psychiatry, Medical University of Graz, Graz, Austria.
authors.forename: Martina
authors.initials: M
authors.lastname: Platzer
authors.affiliation: Department of Psychiatry, Medical University of Graz, Graz, Austria.|Department of Psychology, Karl-Franzens University of Graz, Graz, Austria.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Rieger
authors.affiliation: Department of Psychiatry, Medical University of Graz, Graz, Austria.
authors.forename: Robert
authors.initials: R
authors.lastname: Queissner
authors.affiliation: Department of Psychiatry, Medical University of Graz, Graz, Austria.
authors.forename: Nora
authors.initials: N
authors.lastname: Kainzbauer
authors.affiliation: Department of Psychiatry, Medical University of Graz, Graz, Austria.
authors.forename: Bernd
authors.initials: B
authors.lastname: Reininghaus
authors.affiliation: Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, Ontario, Canada.|Department of Psychiatry and Pharmacology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Roger S
authors.initials: RS
authors.lastname: McIntyre
authors.affiliation: Research Unit on Lifestyle and Inflammation-associated Risk Biomarkers, Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria.
authors.forename: Harald
authors.initials: H
authors.lastname: Mangge
authors.affiliation: Research Unit on Lifestyle and Inflammation-associated Risk Biomarkers, Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria.
authors.forename: Sieglinde
authors.initials: S
authors.lastname: Zelzer
authors.affiliation: Division of Biological Chemistry, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Dietmar
authors.initials: D
authors.lastname: Fuchs
authors.affiliation: Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University Munich, Munich, Germany.
authors.forename: Silvia
authors.initials: S
authors.lastname: Dejonge
authors.affiliation: Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University Munich, Munich, Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Müller
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D001714:Bipolar Disorder / Q000097:blood / Q000150:complications / Q000175:diagnosis / Q000523:psychology; D002318:Cardiovascular Diseases / Q000097:blood / Q000150:complications; D003071:Cognition / Q000502:physiology; D018450:Disease Progression; D016326:Extracellular Matrix Proteins / Q000097:blood*; D005260:Female; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011569:Psychiatric Status Rating Scales; D012720:Severity of Illness Index; D013223:Statistics as Topic
chemical_list: D015415:Biomarkers; D016326:Extracellular Matrix Proteins; D018799:Intercellular Adhesion Molecule-1
keywords: atherosclerosis; bipolar disorder; cardiovascular disease; extracellular matrix proteins; intercellular adhesion molecule; matrix metallopeptidase 9; obesity