title: The CD44 ligand hyaluronic acid is elevated in the cerebrospinal fluid of suicide attempters and is associated with increased blood-brain barrier permeability.
abstract: BACKGROUND
  The glycosaminoglycan hyaluronic acid (HA) is an important component of the extracellular matrix (ECM) in the brain. CD44 is a cell adhesion molecule that binds to HA in the ECM and is present on astrocytes, microglia and certain neurons. Cell adhesion molecules have been reported to be involved in anxiety and mood disorders. CD44 levels are decreased in the cerebrospinal fluid (CSF) of depressed individuals, and the CD44 gene has been identified in brain GWAS studies as a possible risk gene for suicidal behavior.
  
  
  METHODS
  We measured the CSF levels of HA and the soluble CD44 (sCD44) in suicide attempters (n=94) and in healthy controls (n=45) using ELISA and electrochemiluminescence assays. We also investigated other proteins known to interact with CD44, such as osteopontin and the matrix metalloproteinases MMP1, MMP3 and MMP9.
  
  
  RESULTS
  The suicide attempters had higher CSF levels of HA (p=.003) and MMP9 (p=.004). The CSF levels of HA correlated with BBB-permeability (rho=0.410, p<.001) and MMP9 correlated with sCD44 levels (rho=0.260, p=.005).
  
  
  CONCLUSIONS
  Other relevant biological contributors to suicidal behavior is not addressed in parallel to the specific role of CD44-HA signaling. The gender distribution of the patients from whom CSF was analyzed was uneven.
  
  
  CONCLUSIONS
  Increased BBB-permeability and HA levels might be a results of increased neuroinflammation and can play a role in the pathobiology of suicidal behavior. The CD44 signaling pathway might be considered a novel target for intervention in mood disorders.
authors.affiliation: Psychoimmunology Unit, Division of Psychiatry, Department of Clinical Sciences, Lund University, Lund, Sweden; Department of Psychiatry and Behavioral Medicine, Michigan State University, Grand Rapids, Michigan, United States. Electronic address: filip.ventorp@med.lu.se.
authors.forename: F
authors.initials: F
authors.lastname: Ventorp
authors.affiliation: Laboratory of Neuroscience, Felsenstein Medical Research Center, Sackler Faculty of Medicine, Tel Aviv University, Petach-Tikva, Israel; Research Unit at Geha Mental Health Center, Petach-Tikva, Israel.
authors.forename: R
authors.initials: R
authors.lastname: Barzilay
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: S
authors.initials: S
authors.lastname: Erhardt
authors.affiliation: Psychiatry Section, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Samuelsson
authors.affiliation: Psychoimmunology Unit, Division of Psychiatry, Department of Clinical Sciences, Lund University, Lund, Sweden.
authors.forename: L
authors.initials: L
authors.lastname: Träskman-Bendz
authors.affiliation: Psychoimmunology Unit, Division of Psychiatry, Department of Clinical Sciences, Lund University, Lund, Sweden.
authors.forename: S
authors.initials: S
authors.lastname: Janelidze
authors.affiliation: Research Unit at Geha Mental Health Center, Petach-Tikva, Israel; Laboratory of Biological Psychiatry, Felsenstein Medical Research Center, Rabin Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Israel.
authors.forename: A
authors.initials: A
authors.lastname: Weizman
authors.affiliation: Laboratory of Neuroscience, Felsenstein Medical Research Center, Sackler Faculty of Medicine, Tel Aviv University, Petach-Tikva, Israel.
authors.forename: D
authors.initials: D
authors.lastname: Offen
authors.affiliation: Psychoimmunology Unit, Division of Psychiatry, Department of Clinical Sciences, Lund University, Lund, Sweden; Department of Psychiatry and Behavioral Medicine, Michigan State University, Grand Rapids, Michigan, United States; Laboratory of Behavioral Medicine, Van Andel Research Institute, Grand Rapids, Michigan, United States.
authors.forename: L
authors.initials: L
authors.lastname: Brundin
mesh_terms: D000328:Adult; D001812:Blood-Brain Barrier / Q000378:metabolism*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D018960:Hyaluronan Receptors / Q000134:cerebrospinal fluid* / Q000378:metabolism*; D006820:Hyaluronic Acid / Q000134:cerebrospinal fluid* / Q000378:metabolism*; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000134:cerebrospinal fluid; D019278:Matrix Metalloproteinase 3 / Q000134:cerebrospinal fluid; D020780:Matrix Metalloproteinase 9 / Q000134:cerebrospinal fluid; D053495:Osteopontin / Q000134:cerebrospinal fluid; D010539:Permeability; D013406:Suicide, Attempted
chemical_list: D018960:Hyaluronan Receptors; D053495:Osteopontin; D006820:Hyaluronic Acid; C511768:MMP3 protein, human; D019278:Matrix Metalloproteinase 3; D020780:Matrix Metalloproteinase 9; C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1
keywords: CD44; CSF; Hyaluronic acid; Inflammation; MMP9; Suicide