title: Asymmetric dimethylarginine in somatically healthy schizophrenia patients treated with atypical antipsychotics: a case-control study.
abstract: BACKGROUND
  Schizophrenia is associated with increased cardiovascular morbidity and mortality. Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of the nitric oxide synthase, and the L-arginine:ADMA ratio are markers of endothelial dysfunction that predict mortality and adverse outcome in a range of cardiovascular disorders. Increased ADMA levels may also lead to increased oxidative stress. We hypothesized that ADMA and the L-arginine:ADMA ratio are increased in somatically healthy schizophrenia patients treated with atypical antipsychotics (AAP), and that the ADMA and the L-arginine: ADMA ratio are positively correlated to measures of oxidative stress.
  
  
  METHODS
  We included 40 schizophrenia patients treated with AAP, but without somatic disease or drug abuse, and 40 healthy controls. Plasma concentrations of ADMA and L-arginine were determined by high-performance liquid chromatography. Data were related to markers of systemic oxidative stress on DNA, RNA and lipids, as well as measures of medication load, duration of disease and current symptomatology.
  
  
  RESULTS
  Plasma ADMA and the L-arginine:ADMA ratio did not differ between schizophrenia patients and controls. Furthermore, ADMA and the L-arginine:ADMA ratio showed no correlations with oxidative stress markers, medication load, or Positive and Negative Syndrome Scale scores.
  
  
  CONCLUSIONS
  Schizophrenia and treatment with AAP was not associated with increased levels of plasma ADMA or the L-arginine:ADMA ratio. Furthermore, plasma levels of ADMA were not associated with levels of systemic oxidative stress in vivo.
authors.affiliation: Psychiatric Centre Copenhagen, University Hospital of Copenhagen, Copenhagen, Denmark. anders.01.joergensen@regionh.dk.|Department of Neuroscience and Pharmacology, Laboratory of Neuropsychiatry, University of Copenhagen, Copenhagen, Denmark. anders.01.joergensen@regionh.dk.|Psychiatric Centre Copenhagen, University Hospital of Copenhagen, Rigshospitalet, Blegdamsvej 9, DK-2100, Copenhagen, Denmark. anders.01.joergensen@regionh.dk.
authors.forename: Anders
authors.initials: A
authors.lastname: Jorgensen
authors.affiliation: Psychiatric Centre Copenhagen, University Hospital of Copenhagen, Copenhagen, Denmark. Ulla.Knorr@regionh.dk.
authors.forename: Ulla
authors.initials: U
authors.lastname: Knorr
authors.affiliation: Psychiatric Centre Copenhagen, University Hospital of Copenhagen, Copenhagen, Denmark. mhgs@dadlnet.dk.
authors.forename: Mia Greisen
authors.initials: MG
authors.lastname: Soendergaard
authors.affiliation: Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. jopl@sund.ku.dk.
authors.forename: Jens
authors.initials: J
authors.lastname: Lykkesfeldt
authors.affiliation: Psychiatric Centre Copenhagen, University Hospital of Copenhagen, Copenhagen, Denmark. Anders.Fink-Jensen@regionh.dk.|Department of Neuroscience and Pharmacology, Laboratory of Neuropsychiatry, University of Copenhagen, Copenhagen, Denmark. Anders.Fink-Jensen@regionh.dk.|Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. Anders.Fink-Jensen@regionh.dk.
authors.forename: Anders
authors.initials: A
authors.lastname: Fink-Jensen
authors.affiliation: Laboratory of Clinical Pharmacology Q7642, Rigshospitalet, Copenhagen, Denmark. Henrik.Enghusen.Poulsen.01@regionh.dk.|Department of Clinical Pharmacology, Bispebjerg Hospital, Copenhagen, Denmark. Henrik.Enghusen.Poulsen.01@regionh.dk.|Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. Henrik.Enghusen.Poulsen.01@regionh.dk.
authors.forename: Henrik Enghusen
authors.initials: HE
authors.lastname: Poulsen
authors.affiliation: Psychiatric Centre Copenhagen, University Hospital of Copenhagen, Copenhagen, Denmark. Martin.Balslev.Joergensen@regionh.dk.|Department of Neuroscience and Pharmacology, Laboratory of Neuropsychiatry, University of Copenhagen, Copenhagen, Denmark. Martin.Balslev.Joergensen@regionh.dk.|Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. Martin.Balslev.Joergensen@regionh.dk.
authors.forename: Martin Balslev
authors.initials: MB
authors.lastname: Jorgensen
authors.affiliation: Department of Neuroscience and Pharmacology, Laboratory of Neuropsychiatry, University of Copenhagen, Copenhagen, Denmark. Niels.Vidiendal.Olsen@regionh.dk.|Department of Neuroanaesthesia, The Neuroscience Centre, University Hospital of Copenhagen, Rigshospitalet, Copenhagen, Denmark. Niels.Vidiendal.Olsen@regionh.dk.
authors.forename: Niels Vidiendal
authors.initials: NV
authors.lastname: Olsen
authors.affiliation: Department of Neuroscience and Pharmacology, Laboratory of Neuropsychiatry, University of Copenhagen, Copenhagen, Denmark. jmyrup@gmail.com.
authors.forename: Jonatan Myrup
authors.initials: JM
authors.lastname: Staalsø
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D008297:Male; D018384:Oxidative Stress; D012559:Schizophrenia / Q000097:blood* / Q000188:drug therapy*
chemical_list: D014150:Antipsychotic Agents; D015415:Biomarkers; C018524:N,N-dimethylarginine; D001120:Arginine