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.
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.
Leo
Roberto
R
Department of Internal Medicine, University of Rome Tor Vergata, School of Medicine, Rome, Italy. rtoleo@tiscali.it
Di Lorenzo
Giorgio
G
Tesauro
Manfredi
M
Razzini
Cinzia
C
Forleo
Giovanni B
GB
Chiricolo
Gaetano
G
Cola
Clarissa
C
Zanasi
Marco
M
Troisi
Alfonso
A
Siracusano
Alberto
A
Lauro
Renato
R
Romeo
Francesco
F
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
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