title: Nitric Oxide-Related Biological Pathways in Patients with Major Depression.
abstract: 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.
authors.affiliation: Department of Psychiatry, Medical University of Graz, Graz, Austria.|Institute for International Management Practice at ARU Cambridge, Cambridge, United Kingdom.
authors.forename: Andreas
authors.initials: A
authors.lastname: Baranyi
authors.affiliation: Hospital of the Brothers of St. John of God, Graz, Austria.
authors.forename: Omid
authors.initials: O
authors.lastname: Amouzadeh-Ghadikolai
authors.affiliation: Department of Psychiatry, Medical University of Graz, Graz, Austria.
authors.forename: Hans-Bernd
authors.initials: HB
authors.lastname: Rothenhäusler
authors.affiliation: Department of Psychiatry, Medical University of Graz, Graz, Austria.
authors.forename: Simon
authors.initials: S
authors.lastname: Theokas
authors.affiliation: Hospital of the Brothers of St. John of God, Graz, Austria.|Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria.
authors.forename: Christoph
authors.initials: C
authors.lastname: Robier
authors.affiliation: Department of Psychiatry, Medical University of Graz, Graz, Austria.
authors.forename: Maria
authors.initials: M
authors.lastname: Baranyi
authors.affiliation: Department of Psychiatry, Medical University of Graz, Graz, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Koppitz
authors.affiliation: Hospital of the Brothers of St. John of God, Graz, Austria.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Reicht
authors.affiliation: Hospital of the Brothers of St. John of God, Graz, Austria.
authors.forename: Peter
authors.initials: P
authors.lastname: Hlade
authors.affiliation: Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria.
authors.forename: Andreas
authors.initials: A
authors.lastname: Meinitzer
mesh_terms: D000328:Adult; D001119:Arginase / Q000378:metabolism; D001120:Arginine / Q000031:analogs & derivatives / Q000378:metabolism; D001682:Biological Availability; D016022:Case-Control Studies; D003710:Demography; D003865:Major Depressive Disorder / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism*; D011594:Psychometrics; D015398:Signal Transduction
chemical_list: D009569:Nitric Oxide; C024917:symmetric dimethylarginine; C018524:N,N-dimethylarginine; D001120:Arginine; D001119:Arginase