Nitric Oxide-Related Biological Pathways in Patients with Major Depression

PLoS One. 2015 Nov 18;10(11):e0143397. doi: 10.1371/journal.pone.0143397. eCollection 2015.


Background: Major depression is a well-known risk factor for cardiovascular diseases and increased mortality following myocardial infarction. However, biomarkers of depression and increased cardiovascular risk are still missing. The aim of this prospective study was to evaluate, whether nitric-oxide (NO) related factors for endothelial dysfunction, such as global arginine bioavailability, arginase activity, L-arginine/ADMA ratio and the arginine metabolites asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) might be biomarkers for depression-induced cardiovascular risk.

Methods: In 71 in-patients with major depression and 48 healthy controls the Global Arginine Bioavailability Ratio (GABR), arginase activity (arginine/ornithine ratio), the L-arginine/ADMA ratio, ADMA, and SDMA were determined by high-pressure liquid chromatography. Psychiatric and laboratory assessments were obtained at baseline at the time of in-patient admittance and at the time of hospital discharge.

Results: The ADMA concentrations in patients with major depression were significantly elevated and the SDMA concentrations were significantly decreased in comparison with the healthy controls. Even after a first improvement of depression, ADMA and SDMA levels remained nearly unchanged. In addition, after a first improvement of depression at the time of hospital discharge, a significant decrease in arginase activity, an increased L-arginine/ADMA ratio and a trend for increased global arginine bioavailability were observed.

Conclusions: Our study results are evidence that in patients with major depression ADMA and SDMA might be biomarkers to indicate an increased cardiovascular threat due to depression-triggered NO reduction. GABR, the L-arginine/ADMA ratio and arginase activity might be indicators of therapy success and increased NO production after remission.

MeSH terms

  • Adult
  • Arginase / metabolism
  • Arginine / analogs & derivatives
  • Arginine / metabolism
  • Biological Availability
  • Case-Control Studies
  • Demography
  • Depressive Disorder, Major / metabolism*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Nitric Oxide / metabolism*
  • Psychometrics
  • Signal Transduction*


  • Nitric Oxide
  • symmetric dimethylarginine
  • N,N-dimethylarginine
  • Arginine
  • Arginase

Grants and funding

The authors have no support or funding to report.