Gene variant may increase psychiatric risk after traumatic brain injury

May 14, 2018 by Tristan Horrom, Veterans Affairs Research Communications
Dr. Lisa Delano-Wood (right) and her team with VA and the University of California, San Diego, are studying how certain genetic profiles affect outcomes for veterans with traumatic brain injuries. With Delano-Wood are Dr. Victoria Merritt (seated), Nicole Evangelista, and Dr. Scott Sorg. Credit: Kevin Walsh

A variant of the APOE gene may be linked to worse psychiatric symptoms in people who have had a traumatic brain injury, found a Veterans Affairs San Diego Healthcare System study. Study participants with both the gene variant and at least one TBI had more severe symptoms of PTSD, anxiety, and depression than comparison participants.

The results appeared online Feb. 20, 2018, in the Journal of Neurotrauma.

TBI has long been connected with increased risk of such as PTSD, depression, and anxiety. A past study of more than 13,000 veterans by the Minneapolis VA Center for Chronic Disease Outcomes Research found that more than 80 percent of those who had suffered a TBI also had a diagnosis of a psychiatric disorder. The same study found that veterans who had a TBI were three times more likely to have PTSD than those who had not.

The new San Diego study also found that patients with TBI had greater PTSD, depression, and anxiety symptoms than those without. The researchers sought to build on that finding by delving into the biological link between TBI exposure and psychiatric disorders.

Apolipoprotein E is a protein that transports and metabolizes lipids such as cholesterol in the central nervous system. It is involved in the maintenance, growth, and repair of neurons. The protein is encoded by a gene referred to as APOE. APOE has three possible variants. One form of the APOE gene (APOE4) is considered a risk factor for Alzheimer's disease. Previous studies have shown in Vietnam veterans and Iraq/Afghanistan veterans that the APOE4 gene may increase the risk of PTSD.

The researchers set out to test whether the APOE4 gene puts people at greater risk of when combined with TBI. They collected DNA from 133 veterans of the wars in Afghanistan and Iraq to test for the APOE4 gene. Of these participants, 79 had a mild or moderate TBI, while 54 had no TBI history.

In the participant group with TBI, those with the APOE4 gene had significantly higher scores for PTSD, depression, and anxiety, compared with those with a different variant of APOE. The APOE4 variant was linked to worse symptoms for participants with both mild and moderate TBI.

In the group without a TBI, the researchers found no differences in depression, anxiety, and PTSD symptoms between those with or without APOE4.

Dr. Victoria C. Merritt, first author on the paper, concludes, "Genetic risk may help to explain the poorer long-term clinical outcomes often observed in veterans with neurotrauma histories."

The results are interesting because APOE4 seems to be linked to worse psychiatric symptoms only when TBI is involved, according to the researchers. Beyond suggesting a connection between APOE4 and the three conditions studied, the results "also lend support to the broader theory that genetic risk factors influence psychiatric distress following TBI," they write.

The researchers suggest several possible explanations for why those with APOE4 may be at higher risk for psychiatric distress after TBI. First, the APOE4 variant may primarily affect the frontal subcortical regions of the brain, which are often impacted following TBI. These regions are involved in emotion regulation and psychiatric distress. Second, it is possible that APOE4 increases the risk of vascular disease, which has been shown to increase the risk of depression. Third, the presence of APOE4 may cause neurodegenerative effects, whereas the other forms of the gene do not. While more research will be needed to narrow down the cause, "the findings suggest that there may be a [genetic] basis for the complex presentation of symptoms often observed in this vulnerable population," says Merritt.

The study is the first to explore the link between APOE and psychiatric symptoms specifically connected to TBI. More studies are needed to fully understand how this gene interacts with head trauma to contribute to mental health symptoms, say the researchers.

The San Diego VA team is furthering this work by examining the relationship between APOE4 and cognitive outcomes in veterans with and without TBI histories. They are also looking at whether APOE4 affects post-concussion symptoms such as headaches and dizziness. Future research will also examine the how these findings relate to the biology of the brain using advanced neuroimaging methods.

Merritt explains that the work will add important insight on TBI, and may eventually point toward new treatments.

"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 said, "and such work may have relevance to the development of future treatments."

Explore further: An anti-apoE4 specific monoclonal antibody counteracts the pathological effects of apoE4 in vivo

More information: Victoria C. Merritt 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, Journal of Neurotrauma (2018). DOI: 10.1089/neu.2017.5372

Related Stories

An anti-apoE4 specific monoclonal antibody counteracts the pathological effects of apoE4 in vivo

June 30, 2016
The pathological hallmarks of Alzheimer's disease (AD), viz defective Aβ and tau proteins, have been the center of AD-directed therapeutic studies. Although this approach still remains valid, it has not yet produced clinically ...

Study finds gene variant increases risk for depression

July 20, 2017
A University of Central Florida study has found that a gene variant, thought to be carried by nearly 25 percent of the population, increases the odds of developing depression.

Scientists fix genetic risk factor for Alzheimer's disease in human brain cells

April 9, 2018
Using human brain cells, scientists at the Gladstone Institutes discovered the cause of—and a potential solution for—the primary genetic risk factor for Alzheimer's disease, a gene called apoE4.

Newly ID'd role of major Alzheimer's gene suggests possible therapeutic target

September 20, 2017
Nearly a quarter century ago, a genetic variant known as ApoE4 was identified as a major risk factor for Alzheimer's disease—one that increases a person's chances of developing the neurodegenerative disease by up to 12 ...

Alzheimer's gene associated with failure to adapt to cognitive challenge in healthy adults

June 26, 2017
Healthy adults carrying the gene APOE4—the strongest known genetic risk factor for Alzheimer's disease (AD)—may struggle to adapt their brain activity to increasing cognitive demands as they get older, according to a ...

Recommended for you

Early life trauma in men associated with reduced levels of sperm microRNAs

May 22, 2018
Exposure to early life trauma can lead to poor physical and mental health in some individuals, which can be passed on to their children. Studies in mice show that at least some of the effects of stress can be transmitted ...

Training compassion 'muscle' may boost brain's resilience to others' suffering

May 22, 2018
It can be distressing to witness the pain of family, friends or even strangers going through a hard time. But what if, just like strengthening a muscle or learning a new hobby, we could train ourselves to be more compassionate ...

Study finds popular 'growth mindset' educational interventions aren't very effective

May 22, 2018
A new study co-authored by researchers at Michigan State University and Case Western Reserve University found that "growth mindset interventions," or programs that teach students they can improve their intelligence with effort—and ...

Schizophrenics' blood has more genetic material from microbes

May 22, 2018
The blood of schizophrenia patients features genetic material from more types of microorganisms than that of people without the debilitating mental illness, research at Oregon State University has found.

Kids show adult-like intuition about ownership

May 22, 2018
Children as young as age three are able to make judgements about who owns an object based on its location, according to a study from the University of Waterloo.

Age-related racial disparity in suicide rates among US youth

May 21, 2018
New research suggests the suicide rate is roughly two times higher for black children ages 5-12 compared with white children of the same age group. The study, funded by the National Institute of Mental Health (NIMH), appears ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.