Neuroimaging Genetics of Mild TBI

Va Boston Health Care System, Boston MA

Investigators

Linked publications, trials & patents

Abstract

DESCRIPTION (provided by applicant): The wars in Iraq and Afghanistan and recent terrorist events such as the Boston Marathon bombings have put a spotlight on the public health consequences of blast-related traumatic brain injury (TBI). The long-term health costs of blast-induced mTBI are not yet well known, but there has been growing concern over the chronic cognitive and psychological symptoms reported by many returning Veterans including memory problems, headaches, anxiety and personality changes, negative outcomes including suicide and PTSD comorbidity, and the future risk of neurodegenerative disease. Although TBI has been named an invisible wound of the Iraq and Afghanistan wars, new evidence suggests that even mild TBI (mTBI) is associated with measurable damage to brain structure, particularly in neuronal axons comprising white matter of the brain. New brain imaging techniques such as diffusion tensor imaging (DTI) have provided the means to detect subtle changes in white matter not observable with other imaging modalities. However, not everyone who experiences mTBI show obvious alterations in white matter, suggesting that individual differences, including genetic factors, may play a significant role in neurorecovery. Indeed, genes involved in neuronal repair such as APOE and BDNF have been found to influence outcome after TBI. Despite studies linking genetics to functional outcome following TBI, no study has yet examined genetic factors that affect white matter integrity following mTBI. The purpose of the current study is to examine genetic influences on white matter integrity in OEF/OIF/OND Veterans. The primary hypothesis is that individuals who carry the risk variant(s) of genes involved in neuronal repair and modulation of injury extent will have a reduced capacity to engineer a neuroprotective response after brain trauma and, as a result, are more likely to incur loss of white matter integrity. The study will test this hypothesi using data that have been collected as part of a Neuroimaging Genetics Protocol, which encompasses DTI and genetic data from several research labs at the VA Boston Healthcare System including the Translational Research Center for Traumatic Brain Injury and Stress Disorders (TRACTS), National Center for PTSD (NCPTSD), and the Memory Disorders Research Center (MDRC) and has an expected sample size of 300 OEF/OIF/OND Veterans. Veterans with blast-induced mTBI and a deployed, no-TBI group are included in this sample. In the first aim, genetic variants of the APOE, BDNF and COMT genes will be targeted to examine the extent to which they moderate the association between mTBI and white matter integrity. In the second aim, additional gene variants putatively involved in neuronal repair and neural reserve will be examined to discover novel influences on mTBI and white matter. The third aim will examine neurodegenerative disease risk variants on DTI. If the study hypotheses are supported, it could pave the way for customized assessment and treatment plans tailored to an individual's neurobiology.