P-selectin in Major Depression: Preliminary Findings with Venlafaxine Treatment

Piletz, John E.; Halaris, Angelos; Iqbal, Omer; Hoppensteadt, Debra; Fareed, Jawed; Zhu, He; Sinacore, James; DeVane, C. Lindsay
April 2010
International Journal of Health Science;Apr-Jun2010, Vol. 3 Issue 2, p312
Academic Journal
Background Disturbances in affective state are known to cause platelet activation, which may relate to evidence linking major depression and coronary artery disease. The platelet activation biomarker, P-selectin, exists in various blood fractions that demarcate steps of platelet activation. If circulating platelets are more activated in depressed patients, the literature suggests that amongst antidepressant classes, the Serotonin- Selective Reuptake Inhibitors (SSRIs) are best able to normalize this abnormality. Serotonin/ Norepinephrine Reuptake Inhibitors (SNRIs), like venlafaxine, have not been studied in this regard. Aim of the Study To determine the status of activated P-selectin (platelet surface- bound and/or released forms) in depressed patients before and after 8 weeks of treatment with the SNRI, venlafaxine. Methods Baseline (untreated) subjects were major depressives (n= 23) and age/sex-matched healthy controls (n= 17) with no evidence of coronary artery disease. A subgroup of the depressed cohort (n= 15) was restudied after 4 and 8 weeks on venlafaxine. P-selectin levels were compared to two biomarkers not known to change during platelet activation: the membranous fibronectin-signaling protein, IRAS, and the antigen of the GPIIb/IIIa receptor, CD61. Results At baseline, both activated forms of P-Selectin were high in the depressives, but only the soluble form showed statistical significance (p= 0.03) versus healthy controls. Venlafaxine treatment led to mood normalization based on reduced Hamilton Depression scores (p< 0.0001), while the level of soluble P-selectin was non-significantly lowered (p= 0.13). Platelet membranous IRAS and CD61 levels were normal at baseline but down-regulated after 4 and 8 weeks of treatment (p = 0.01 each). Conclusion High levels of soluble P-selectin were identified in depression, indicative of platelet activation. Venlafaxine treatment had minimal effect on soluble P-selectin but had clear effects on platelet IRAS and CD61. Therefore, platelet activation does not readily normalize with mood correction after 8 weeks on venlafaxine, but other platelet effects seem to occur.


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