Elevated P-selectin on platelets in depression: response to bupropion.
Increased platelet activation has been suggested as a possible reason for the increased vulnerability of depressed patients to ischemic heart disease (IHD). Translocation of P-selectin, an integral alpha-granule membrane protein, to the platelet surface is a measure of platelet activation. Herein, western blots of platelet plasma membranes containing P-selectin were quantified in patients with major depression (n=19; mean age=39 +/- 2 years) and healthy comparison subjects (n=17; mean age=36 +/- 2 years). None evidenced clinical signs of IHD, and only two patients had a lifestyle IHD risk factor (smoking). Blood was obtained from all 19 depressed patients before treatment, and 15 returned after 6-8 weeks of open-label bupropion treatment. Bupropion was chosen as the antidepressant because it did not elevate plasma norepinephrine or serotonin, endogenous agonists that can induce platelet degranulation. Western blotting revealed more P-selectin immunoreactivity (75 kD band) in depressed patients compared to healthy controls (P=0.003). After bupropion treatment, P-selectin remained high in depressed patients. beta3-Integrin, a reference plasma membrane protein that does not translocate during activation, was of equivalent density in depressed patients and healthy control subjects, and was unchanged after treatment with bupropion. P-Selectin failed to correlate with severity of illness based on the Hamilton Depression scale, or with the post-treatment plasma concentration of bupropion. The results suggest an elevation in P-selectin on platelet plasma membranes might be a trait marker for depression.
Piletz
J E
JE
Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Room. G128, 2500 North State Street, Jackson, MS 39216-4505, USA. jpiletz@psychiatry.umsmed.edu
Zhu
H
H
Madakasira
S
S
Pazzaglia
P
P
Lindsay DeVane
C
C
Goldman
N
N
Halaris
A
A
D000293:Adolescent; D000328:Adult; D000928:Antidepressive Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D016642:Bupropion / Q000494:pharmacology* / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000097:blood* / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D019007:P-Selectin / Q000097:blood* / Q000187:drug effects; D015539:Platelet Activation / Q000187:drug effects*
D000928:Antidepressive Agents; D019007:P-Selectin; D016642:Bupropion