title: NOS1AP is associated with increased severity of PTSD and depression in untreated combat veterans.
abstract: BACKGROUND
  Posttraumatic stress disorder (PTSD) and depressive disorder are over represented in combat veterans. Veterans with both disorders have an increased risk of suicide. The nitric oxide synthase 1 adaptor protein (NOS1AP) gene, which modulates stress-evoked N-methyl-d-aspartate (NMDA) activity, was investigated in combat veterans.
  
  
  METHODS
  A comprehensive genetic analysis of NOS1AP and its association with PTSD was investigated in Vietnam combat veterans with PTSD (n=121) and a group of healthy control individuals (n=237). PTSD patients were assessed for symptom severity and level of depression using the Mississippi Scale for Combat-Related PTSD and the Beck Depression Inventory-II (BDI).
  
  
  RESULTS
  The G allele of NOS1AP SNP rs386231 was significantly associated with PTSD (p=0.002). Analysis of variance revealed significant differences in BDI-II and Mississippi scores between genotypes for rs386231 with the GG genotype associated with increased severity of depression (p=0.002 F=6.839) and higher Mississippi Scale for Combat-Related PTSD scores (p=0.033). Haplotype analysis revealed that the C/G haplotype (rs451275/rs386231) was significantly associated with PTSD (p=0.001).
  
  
  CONCLUSIONS
  The sample sizes in our study were not sufficient to detect SNP associations with very small effects. In addition the study was limited by its cross sectional design.
  
  
  CONCLUSIONS
  This is the first study reporting that a variant of the NOS1AP gene is associated with PTSD. Our data also suggest that a genetic variant in NOS1AP may increase the susceptibility to severe depression in patients with PTSD and increased risk for suicide.
authors.affiliation: Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia.
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Lawford
authors.forename: Charles P
authors.initials: CP
authors.lastname: Morris
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Swagell
authors.forename: Ian P
authors.initials: IP
authors.lastname: Hughes
authors.forename: Ross McD
authors.initials: RM
authors.lastname: Young
authors.forename: Joanne
authors.initials: J
authors.lastname: Voisey
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D003130:Combat Disorders / Q000235:genetics* / Q000378:metabolism; D003863:Depression / Q000235:genetics* / Q000378:metabolism; D003866:Depressive Disorder / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016202:N-Methylaspartate / Q000378:metabolism; D013313:Stress Disorders, Post-Traumatic / Q000235:genetics* / Q000378:metabolism / Q000523:psychology; D014728:Veterans / Q000523:psychology*; D047829:Vietnam Conflict
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C488081:NOS1AP protein, human; D016202:N-Methylaspartate