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Clinical Topics

Gene variant plus TBI worsens symptoms

by U.S. Medicine

July 14, 2018

SAN DIEGO — A gene variant used to predict Alzheimer’s disease also appears to signal worse psychiatric symptoms in patients who have suffered a traumatic brain injury (TBI), a new study reported.

The results published online by the Journal of Neurotrauma found that study participants with both the gene variant and at least one TBI had more severe symptoms of post-traumatic stress disorder (PTSD), anxiety and depression than a control group.1

Based on past research noting that more than 80% of veterans with TBI also had a psychiatric disorder diagnosis, VA San Diego Healthcare System-led researchers sought to determine whether the APOE4 gene puts people at greater risk of psychiatric distress when combined with TBI.

Apolipoprotein E, a protein that transports and metabolizes lipids such as cholesterol in the central nervous system, is involved in the maintenance, growth and repair of neurons. The protein is encoded by the APOE, a form of which—APOE4—is deemed a risk factor for Alzheimer’s disease. Past research has indicated that the APOE4 gene may increase the risk of PTSD in veterans serving in Vietnam, Iraq and Afghanistan.

For the study, the researchers collected DNA from 133 veterans of the wars in Afghanistan and Iraq—79 with mild or moderate TBI, as well as 54 with no TBI history—to test for the APOE4 gene.

Results indicated that patients with TBI and the APOE4 gene had significantly higher symptom scores for PTSD, depression and anxiety compared with those with a different variant of APOE, with no discernible difference between mild or moderate TBI.

At the same time, the presence of the APOE4 variant did not appear to make any difference in symptoms in the group without TBI.

“Genetic risk may help to explain the poorer long-term clinical outcomes often observed in veterans with neurotrauma histories,” explained first author Victoria C. Merritt, PhD.

Study authors suggested that the results bolster theories that “that genetic risk factors influence psychiatric distress following TBI,” positing that the APOE4 variant may primarily affect the frontal subcortical regions of the brain, that APOE4 increases the risk of vascular disease or that the presence of APOE4 might cause neurodegenerative effects, whereas the other forms of the gene do not.

More research is needed to pinpoint the relationship, Merritt said, but “the findings suggest that there may be a [genetic] basis for the complex presentation of symptoms often observed in this vulnerable population.”

“Ultimately, we feel that this research is essential to developing a more complete understanding of the multitude of factors that impact recovery following neurotrauma,” she added, “and such work may have relevance to the development of future treatments.”


1Merritt VC, Clark AL, Sorg SF, Evangelista ND, et al. Apolipoprotein E (APOE) ε4 Genotype is Associated with Elevated Psychiatric Distress in Veterans with a History of Mild to Moderate Traumatic Brain Injury. J Neurotrauma. 2018 Feb 20. doi: 10.1089/neu.2017.5372.[Epub ahead of print] PubMed PMID: 29463164.

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