title: Multi-level biomarker analysis of nitric oxide synthase isoforms in bipolar disorder and adult ADHD.
abstract: BACKGROUND
  Several studies have shown altered levels of nitric oxide (NO) and its stable metabolites (NOx (-)) in blood and cerebrospinal fluid of psychiatric patients. The aim of our study was to replicate previous findings and investigate the influence of the nitrinergic system in bipolar disorder and adult attention-deficit/hyperactivity disorder (aADHD) in particular.
  
  
  METHODS
  The concentrations of NO2 (-) and NO3 (-) in peripheral blood in a sample of aADHD, bipolar disorder (BPD) and controls were analysed. The sample was genotyped for a three marker haplotype in the NOS3 gene (rs2070744, rs1799983 and Intron 4 VNTR) and for genetic variants of the NOS1 gene (NOS1 ex 1c, NOS1 ex 1f). Finally, qRT PCR was performed.
  
  
  RESULTS
  We found significantly lower NOx (-) levels in BPD (p<0.001). rs2070744 T/T-carriers of the whole sample showed increased mRNA expression of NOS3 (p=0.05). Only in BPD an influence of rs2070744 was seen regarding NO metabolite levels; C/C carriers displayed lower NOx (-) levels (p=0.05).
  
  
  CONCLUSIONS
  We could replicate and extend previous findings showing altered NOx (-) levels in BPD and an influence of NOS3 rs2070744 on NOS3 expression and NOx (-) concentration. Together, these data point to a role of the nitrinergic pathway in BPD.
authors.affiliation: Department of Psychiatry, Psychosomatics and Psychotherapy, Johann Wolfgang Goethe University Frankfurt, Frankfurt, Germany Comprehensive Heart Failure Center, University of Würzburg, Würzburg, Germany Sarah.Kittel-Schneider@kgu.de.
authors.forename: Sarah
authors.initials: S
authors.lastname: Kittel-Schneider
authors.affiliation: Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Würzburg, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Reuß
authors.affiliation: Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Würzburg, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Meyer
authors.affiliation: IZKF Microarray Core Unit, University of Würzburg, Würzburg, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Weber
authors.affiliation: Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Würzburg, Germany.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Gessner
authors.affiliation: Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Würzburg, Germany.
authors.forename: Carolin
authors.initials: C
authors.lastname: Leistner
authors.affiliation: Department of Psychiatry, Psychosomatics and Psychotherapy, Johann Wolfgang Goethe University Frankfurt, Frankfurt, Germany.
authors.forename: Juliane
authors.initials: J
authors.lastname: Kopf
authors.affiliation: Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Würzburg, Germany.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Schmidt
authors.affiliation: Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Würzburg, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Hempel
authors.affiliation: Department of Psychiatry, Psychosomatics and Psychotherapy, Johann Wolfgang Goethe University Frankfurt, Frankfurt, Germany Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Würzburg, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Volkert
authors.affiliation: Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Würzburg, Germany.
authors.forename: Klaus-Peter
authors.initials: KP
authors.lastname: Lesch
authors.affiliation: Department of Psychiatry, Psychosomatics and Psychotherapy, Johann Wolfgang Goethe University Frankfurt, Frankfurt, Germany Comprehensive Heart Failure Center, University of Würzburg, Würzburg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Reif
mesh_terms: D000328:Adult; D001289:Attention Deficit Disorder with Hyperactivity / Q000097:blood / Q000235:genetics*; D015415:Biomarkers / Q000097:blood; D001714:Bipolar Disorder / Q000097:blood / Q000235:genetics*; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000097:blood*; D052248:Nitric Oxide Synthase Type I / Q000097:blood / Q000235:genetics*; D052250:Nitric Oxide Synthase Type III / Q000097:blood / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult
chemical_list: D015415:Biomarkers; D009569:Nitric Oxide; C496314:NOS3 protein, human; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III
keywords: Nitric oxide; attention deficit-hyperactivity disorder; biomarkers; bipolar disorder; genetic polymorphism