title: Association between enhanced soluble CD40 ligand and proinflammatory and prothrombotic states in major depressive disorder: pilot observations on the effects of selective serotonin reuptake inhibitor therapy.
abstract: OBJECTIVE
  Major depressive disorder (MDD) is associated with low-grade inflammation, and it is considered a risk factor for coronary artery disease (CAD). CD40 ligand (CD40L) plays an important role in inflammation, platelet activation, and clotting system activation. We investigated soluble CD40L (sCD40L) expression in MDD and assessed whether it may represent a molecular mechanism that links inflammation and a prothrombotic state and whether this condition may be modified by selective serotonin reuptake inhibitor (SSRI) therapy.
  
  
  METHODS
  Levels of sCD40L, interleukin-1beta (IL-1beta), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), soluble P-selectin (sP-selectin), activated factor VII (FVIIa), and prothrombin fragment 1+2 (F1+2) were measured in 46 drug-naïve, first-episode MDD patients without conventional CAD risk factors and in 46 matched healthy controls. Participants were screened between March 2002 and November 2005. Twenty of the 46 MDD patients were then randomly assigned to either sertraline 100 mg/day (N = 10) or citalopram 20 mg/day (N = 10); the aforementioned variables were measured at baseline and after 6 weeks of treatment.
  
  
  RESULTS
  Compared with control subjects, MDD patients had higher baseline levels of sCD40L, IL-1beta, IL-6, TNF-alpha, sP-selectin, FVIIa, and F1+2. In the clinical group, sCD40L levels, HAM-D total scores, and proinflammatory markers were strongly intercorrelated. In contrast, there were no significant correlations in the control group. Mood improvement achieved with SSRI therapy was associated with significant reduction in sCD40L, proinflammatory markers, and prothrombotic markers expression. (All p values < .0001.)
  
  
  CONCLUSIONS
  This pilot study shows that CD40/ CD40L pathway up-regulation in MDD patients relates increased levels of sCD40L to a prothrombotic state and, preliminarily, indicates that SSRI therapy may significantly reduce sCD40L and CD40L levels associated with proinflammatory and prothrombotic states.
authors.affiliation: Department of Internal Medicine, University of Rome Tor Vergata, School of Medicine, Rome, Italy. rtoleo@tiscali.it
authors.forename: Roberto
authors.initials: R
authors.lastname: Leo
authors.forename: Giorgio
authors.initials: G
authors.lastname: Di Lorenzo
authors.forename: Manfredi
authors.initials: M
authors.lastname: Tesauro
authors.forename: Cinzia
authors.initials: C
authors.lastname: Razzini
authors.forename: Giovanni B
authors.initials: GB
authors.lastname: Forleo
authors.forename: Gaetano
authors.initials: G
authors.lastname: Chiricolo
authors.forename: Clarissa
authors.initials: C
authors.lastname: Cola
authors.forename: Marco
authors.initials: M
authors.lastname: Zanasi
authors.forename: Alfonso
authors.initials: A
authors.lastname: Troisi
authors.forename: Alberto
authors.initials: A
authors.lastname: Siracusano
authors.forename: Renato
authors.initials: R
authors.lastname: Lauro
authors.forename: Francesco
authors.initials: F
authors.lastname: Romeo
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D023201:CD40 Ligand / Q000378:metabolism*; D015283:Citalopram / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology*; D015942:Factor VIIa / Q000378:metabolism; D005260:Female; D006801:Humans; D007249:Inflammation / Q000209:etiology / Q000503:physiopathology*; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D019007:P-Selectin / Q000378:metabolism; D010865:Pilot Projects; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*; D020280:Sertraline / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D023201:CD40 Ligand; D015283:Citalopram; D015942:Factor VIIa; D053583:Interleukin-1beta; D019007:P-Selectin; D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline; D014409:Tumor Necrosis Factor-alpha