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
J Clin Psychiatry 2006;67(11):1760-1766
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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.
Method: 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.