Posttraumatic stress disorder (PTSD) and mild traumatic brain injury (mTBI) are common and often disabling conditions affecting many veterans of Operations Iraqi Freedom (OIF), Enduring Freedom (OEF), and New Dawn (OND). Emerging evidence suggests that both conditions are associated with elevated levels of central and peripheral oxidative stress (OXS) and inflammation (INF). For this proposal, we have assembled a unique team of investigators with expertise in molecular genetics and magnetic resonance spectroscopy (MRS) to study these processes in relation to chronic PTSD and mTBI. The study will draw from a large and psychiatrically heterogeneous cohort of veterans of OIF/OEF/OND, now on average 10 years post-deployment, with genome-wide genotype data available from a previous assessment. We will acquire new MRS scans for analysis in combination with the genomic data to examine associations of PTSD and mTBI with neural and peripheral indices of OXS and INF and identify genomic sources of individual differences in these associations. More specifically, the primary aims are to (a) examine associations between current PTSD, history of mTBI, and MRS measures of OXS and INF, (b) interrogate genes in the OXS and INF pathways to identify genetic moderators of the associations between PTSD, mTBI and MRS parameters, and (c) examine associations between MRS measures of OXS and INF, other MRI indices of neural integrity, and peripheral markers of OXS and INF. The ultimate goal of this study is to identify neurobiological pathways that can be used in the future to guide the development of blood panels and/or neuroimaging protocols for clinical assessment, as well as molecular targets for pharmacologic intervention for veterans suffering from chronic PTSD and mTBI.

Public Health Relevance

Posttraumatic stress disorder (PTSD) and mild traumatic brain injury (mTBI) are common and disabling conditions affecting many veterans of recent deployments. Studies suggest that both conditions are associated with the development of central and peripheral oxidative stress (OXS) and inflammation (INF). This study will use magnetic resonance spectroscopy to examine associations of PTSD, mTBI, and their interaction with neuroimaging measures of OXS and INF. We will interrogate genes in the OXS and INF pathways to identify loci that account for individual differences in these associations. This proposal seeks to address a gap in the diagnosis and treatment of veterans by identifying neurometabolic signatures and genetic pathways associated with mTBI and PTSD.

Agency
National Institute of Health (NIH)
Institute
Veterans Affairs (VA)
Type
Non-HHS Research Projects (I01)
Project #
1I01CX001586-01A1
Application #
9451622
Study Section
Neurobiology C (NURC)
Project Start
2018-01-01
Project End
2021-12-31
Budget Start
2018-01-01
Budget End
2018-12-31
Support Year
1
Fiscal Year
2018
Total Cost
Indirect Cost
Name
VA Boston Health Care System
Department
Type
DUNS #
034432265
City
Boston
State
MA
Country
United States
Zip Code