Apolipoprotein E epsilon 4 Genotype Is Associated with Elevated Psychiatric Distress in Veterans with a History of Mild to Moderate Traumatic Brain Injury

摘要

As few studies have examined the relationship between the apolipoprotein E (APOE) gene and clinical outcomes after military-related traumatic brain injury (TBI), we aimed to determine whether the epsilon 4 allele of the APOE gene influences neuropsychiatric symptoms in veterans with a history of mild-to-moderate TBI. Participants included 133 veterans (TBI=79; military controls [MC]=54) who underwent APOE genotyping and were divided into epsilon 4(+) (TBI=18; MC=15) and epsilon 4(-) (TBI=61; MC=39) groups. All participants underwent evaluation of psychological distress using the Beck Depression Inventory-II, Beck Anxiety Inventory, and PTSD Checklist-Military Version. Two-way analyses of variance were conducted to examine the effect of group (TBI vs. MC) and APOE-is an element of 4 status (epsilon 4(+) vs. epsilon 4(-)) across symptom measures. There was a significant main effect of group across all symptom measures (TBI MC; all p values 0.001), no main effect of epsilon 4 genotype (p=0.152-0.222), and a significant interaction of group by epsilon 4 genotype across all measures (p=0.027-0.047). Specifically, for TBI participants, epsilon 4(+) veterans demonstrated significantly higher symptom scores across all measures when compared to epsilon 4(-) veterans (p=0.007-0.015). For MC participants, epsilon 4 status had no effect on the severity of psychiatric symptom scores (p=0.585-0.708). Our results demonstrate that, in our well-characterized sample of veterans with history of neurotrauma, possession of the epsilon 4 allele conveys risk for increased symptomatology (i.e., depression, anxiety, and post-traumatic stress disorder), even well outside of the acute phase of injury. Findings suggest a meaningful relationship between APOE genotype and psychiatric distress post-TBI, and they suggest that there is a brain basis for the complex neuropsychiatric presentation often observed in this vulnerable population. Future longitudinal studies are needed in order to further our understanding of how genetic factors influence response to TBI.