Citation

Lawford BR, Morris CP, Swagell CD, Hughes IP, Young RM, Voisey J. J. Affect. Disord. 2013; 147(1-3): 87-93.

Affiliation

Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia; Greenslopes Private Hospital, Brisbane, Queensland, Australia.

Copyright

(Copyright © 2013, Elsevier Publishing)

DOI

10.1016/j.jad.2012.10.013

PMID

23146198

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). LIMITATIONS: 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.

Language: en