Nitric oxide pathway genes (NOS1AP and NOS1) are involved in PTSD severity, depression, anxiety, stress and resilience

Dagmar Bruenig; Charles P Morris; Divya Mehta; Wendy Harvey; Bruce Lawford; Ross McD Young; Joanne Voisey

doi:10.1016/j.gene.2017.04.048

Nitric oxide pathway genes (NOS1AP and NOS1) are involved in PTSD severity, depression, anxiety, stress and resilience

Gene. 2017 Aug 20:625:42-48. doi: 10.1016/j.gene.2017.04.048. Epub 2017 Apr 29.

Authors

Dagmar Bruenig¹, Charles P Morris², Divya Mehta³, Wendy Harvey⁴, Bruce Lawford³, Ross McD Young³, Joanne Voisey⁵

Affiliations

¹ Institute of Health and Biomedical Innovation (IHBI) and School of Biomedical Sciences, 60 Musk Avenue, Queensland University of Technology, Kelvin Grove, Queensland 4059, Australia; Gallipoli Medical Research Institute, Greenslopes Private Hospital, Newdegate Street, Greenslopes QLD 4120, Australia.
² Institute of Health and Biomedical Innovation (IHBI) and School of Psychology and Counselling, 60 Musk Avenue, Queensland University of Technology, Kelvin Grove, Queensland 4059, Australia.
³ Institute of Health and Biomedical Innovation (IHBI) and School of Biomedical Sciences, 60 Musk Avenue, Queensland University of Technology, Kelvin Grove, Queensland 4059, Australia.
⁴ Gallipoli Medical Research Institute, Greenslopes Private Hospital, Newdegate Street, Greenslopes QLD 4120, Australia.
⁵ Institute of Health and Biomedical Innovation (IHBI) and School of Biomedical Sciences, 60 Musk Avenue, Queensland University of Technology, Kelvin Grove, Queensland 4059, Australia. Electronic address: j.voisey@qut.edu.au.

PMID: 28465168
DOI: 10.1016/j.gene.2017.04.048

Abstract

The nitric oxide pathway in the hippocampus is involved in the biological stress response with detrimental consequences to cells and HPA axis feedback. Hippocampal atrophy and HPA axis feedback dysfunction are associated with posttraumatic stress disorder (PTSD). This study systematically investigates two genes of the nitric oxide pathway NOS1AP and NOS1 for a potential involvement in PTSD, comorbidities and resilience. A cohort of age and gender matched Vietnam veterans including trauma-exposed cases and controls was recruited and comprehensively assessed (n=299). A total of 49 NOS1AP and 16 NOS1 polymorphisms were analysed and genotypes correlated with gold standard clinical measures to assess PTSD severity and related phenotypes (depression, anxiety, stress, resilience) based on diagnostic status. Multiple NOS1AP polymorphisms were associated across all measures, and NOS1 polymorphisms were associated with PTSD severity, stress and resilience. The GG genotype of NOS1 polymorphism rs10744891 was associated with PTSD severity (surviving multiple correction) while the combined TT-TG genotypes were associated with resilience (p=0.005; p=0.033, respectively). This study indicates that NOS1AP and NOS1 from the nitric oxide pathway are likely to play a key role in PTSD, its comorbidities and resilience. Given the essential role of NOS1AP and NOS1 in stress response they may be reliable targets for screening and intervention strategies.

Keywords: Anxiety; Depression; NOS1; NOS1AP; PTSD; Resilience.

MeSH terms

Adaptor Proteins, Signal Transducing / genetics*
Aged
Anxiety / complications
Anxiety / genetics*
Case-Control Studies
Depression / complications
Depression / genetics*
Humans
Male
Middle Aged
Nitric Oxide Synthase Type I / genetics*
Polymorphism, Single Nucleotide
Resilience, Psychological*
Stress Disorders, Post-Traumatic / complications
Stress Disorders, Post-Traumatic / genetics*
Veterans
Vietnam Conflict

Substances

Adaptor Proteins, Signal Transducing
NOS1AP protein, human
NOS1 protein, human
Nitric Oxide Synthase Type I