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NOS1AP is associated with increased severity of PTSD and depression in untreated combat veterans

Lawford, Bruce R., Morris, Charles P., Swagell, Christopher D. , Hughes, Ian P. , Young, Ross McD., & Voisey, Joanne (2013) NOS1AP is associated with increased severity of PTSD and depression in untreated combat veterans. Journal of Affective Disorders, 147(1-3), pp. 87-93.

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    Abstract

    Background

    Post traumatic 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.

    Impact and interest:

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    ID Code: 55208
    Item Type: Journal Article
    Keywords: polymorphism, genetics, PTSD, depression, Nitric oxide synthase 1 adaptor protein
    DOI: 10.1016/j.jad.2012.10.013
    ISSN: 0165-0327
    Subjects: Australian and New Zealand Standard Research Classification > BIOLOGICAL SCIENCES (060000) > BIOCHEMISTRY AND CELL BIOLOGY (060100)
    Australian and New Zealand Standard Research Classification > BIOLOGICAL SCIENCES (060000) > GENETICS (060400) > Neurogenetics (060410)
    Australian and New Zealand Standard Research Classification > PSYCHOLOGY AND COGNITIVE SCIENCES (170000) > PSYCHOLOGY (170100) > Biological Psychology (Neuropsychology Psychopharmacology Physiological Psychology) (170101)
    Divisions: Current > QUT Faculties and Divisions > Faculty of Health
    Current > Institutes > Institute of Health and Biomedical Innovation
    Copyright Owner: Copyright 2012 Elsevier BV
    Copyright Statement: This is the author’s version of a work that was accepted for publication in Journal of Affective Disorders. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Journal of Affective Disorders, [VOL 147, ISSUE 1-3, (2013)] DOI: 10.1016/j.jad.2012.10.013
    Deposited On: 30 Nov 2012 11:54
    Last Modified: 02 Apr 2014 20:42

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