Decreased platelet nitric oxide synthase activity and plasma nitric oxide metabolites in major depressive disorder

Biol Psychiatry. 2004 Jul 15;56(2):129-34. doi: 10.1016/j.biopsych.2004.03.003.


Background: Major depression (MD) has been associated with increased cardiovascular mortality in patients with coronary heart disease (CHD) and has been described as an independent risk factor for the development of CHD in healthy subjects; however, the mechanism of the association between MD and CHD remains to be determined. Nitric oxide (NO) plays a major role in cardiovascular regulation, and decreased NO production has been associated with several cardiovascular risk factors. We hypothesized that in patients with MD, NO production by both platelets and the endothelium would be reduced when compared with healthy control subjects (HCs).

Methods: Blood samples were obtained from 15 subjects with MD and 16 HCs with no known history of cardiovascular illness. Plasma NO metabolite (NOx) levels were analyzed by chemiluminescence. Platelet endothelial NO synthase (eNOS) activity was examined through the conversion of l-[(14)C]arginine to l-[(14)C]citrulline.

Results: The levels of both plasma NOx and platelet eNOS activity were significantly lower in subjects with MD compared with HCs.

Conclusions: These data suggest that decreased NO production by the vascular wall and platelets might contribute to the increased CHD risk observed in patients with MD.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Anxiety Disorders / blood
  • Anxiety Disorders / complications
  • Anxiety Disorders / physiopathology
  • Biopterin / analogs & derivatives*
  • Biopterin / blood
  • Blood Platelets / enzymology*
  • Depressive Disorder, Major / blood*
  • Depressive Disorder, Major / complications
  • Depressive Disorder, Major / physiopathology
  • Female
  • Humans
  • Male
  • Nitrates / blood
  • Nitric Oxide / blood*
  • Nitric Oxide Synthase / metabolism*
  • Nitric Oxide Synthase Type III
  • Nitrites / blood
  • Reference Values


  • Nitrates
  • Nitrites
  • Biopterin
  • Nitric Oxide
  • NOS3 protein, human
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type III
  • sapropterin