Apolipoprotein E ε4 Genotype Is Associated with Elevated Psychiatric Distress in Veterans with a History of Mild to Moderate Traumatic Brain Injury.

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 ε4 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 ε4 ⁺ (TBI = 18; MC = 15) and ε4 ^- (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-ε4 status (ε4 ⁺ vs. ε4 ^- ) 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 ε4 genotype (p = 0.152-0.222), and a significant interaction of group by ε4 genotype across all measures (p = 0.027-0.047). Specifically, for TBI participants, ε4 ⁺ veterans demonstrated significantly higher symptom scores across all measures when compared to ε4 ^- veterans (p = 0.007-0.015). For MC participants, ε4 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 ε4 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.