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Cracking the code for resilience

A VCU School of Medicine researcher is exploring the genetic underpinnings of trauma responses in the hope of improving mental health care.

Using a novel statistical model, VCU’s Ananda Amstadter and her team have found that about 50% of resilience can be explained by genetic factors. (Getty Images)
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Given current events ranging from the ongoing pandemic to giant wildfires and powerful hurricanes, it’s not surprising that many people find their emotional reserves are depleted. Statistics from the Kaiser Family Foundation show that about 4 in 10 adults in the U.S. have reported symptoms of anxiety or depressive disorder during the COVID-19 pandemic, up from 1 in 10 adults who reported these symptoms in the first half of 2019.

Such trends are concerning. They also illustrate just how different individuals’ responses to stress and trauma can be.

How are some people better able to cope? At least part of that answer lies in their DNA, according to Ananda Amstadter, Ph.D., an associate professor in the VCU School of Medicine’s Department of Psychiatry and the Virginia Institute for Psychiatric and Behavioral Genetics.

“Genes and family history set everyone on a slightly different trajectory,” Amstadter said. “Some people thrive and actually have post-traumatic growth, whereas other people have debilitating symptoms that tend to be persistent until we treat them.”

Finding the source

For more than a decade, Amstadter has been researching the genetic-environmental interplay involved in post-traumatic stress disorder and its inverse, resilience.

“From my early days as an undergraduate, I was passionate about understanding how our biologic nature interacts with environmental events, such as trauma, to better understand who’s at risk of really severe outcomes and suffering versus who’s resilient,” Amstadter said. “If we can understand the resilience spectrum for traumatic stress and PTSD by identifying the specific genetic variants and their biologic pathways, we could be better at preventing and treating mental health conditions related to trauma and traumatic stress.” [View Image]Ananda Amstadter, Ph.D.

To start to distinguish between the genetic and environmental underpinnings of resilience, Amstadter and her colleagues developed a novel statistical model based on data from one of the Virginia Institute for Psychiatric and Behavioral Genetics’ twin registries. This registry provides information about stressful life events twins experienced — some traumatic, some not — as well as any mental health issues. From that, Amstadter and her colleagues built a model that essentially totals the different stressors and predicts the development of internalizing symptoms, such as anxiety, worry and sadness.

“We then look at the deviation between where we would predict somebody would be given how much stress they’ve experienced versus where they actually are,” Amstadter said. “So, for people who have had a very high dose of stress and are functioning better than would be expected, the difference is their ‘degree of resilience,’ if you will.”

Using this model, Amstadter and her colleagues have found that resilience is “moderately heritable” — meaning about 50% can be explained by genetic factors — and that a person’s degree of resilience remains largely stable over time.

A product of personality?

What is it in a person’s DNA that influences their ability to cope in the face of adversity? Is resilience simply a byproduct of specific personality traits or an inherited risk for developing mental health conditions like depression or anxiety?

According to Amstadter’s research, there is some overlap between specific personality traits and a person’s degree of resilience. Greater levels of resilience are associated with optimism, self-esteem and mastery, whereas lower levels of resilience are correlated with neuroticism and interpersonal dependency. Such personality traits only account for 7% to 60% of the genetic component of resilience, though, which means there are other genetic factors at play and potentially genes specific to resilience that have yet to be discovered.

In the same way, resilience only moderately overlaps with a person’s genetic risk for developing major depression, generalized anxiety disorder, alcohol abuse or dependence or antisocial personality disorder. However, according to Amstadter and her colleagues, a lower level of resilience is not directly responsible for someone developing these conditions, hinting that teaching someone healthy coping skills could mitigate at least some of the risk of developing mental health issues following a traumatic event.

“I think I would be downtrodden in this field if we thought the environment didn’t matter,” Amstadter said. “Because that’s what people have more control over.”

DNA, not destiny

In many ways, resilience is like a toolbox that people can use in the wake of a stressful or traumatic event. Genes supply some of those tools (and some people have more than others) but additional tools can be gained through things like social support, developing healthy coping skills, becoming more aware of stress reactions and joining self-help groups.

Knowing how “full” someone’s resilience toolbox is at both a genetic and environmental level could help lead to better prevention and treatment for conditions such as post-traumatic stress disorder. It could help improve the allocation of often scarce mental health resources, especially in the wake of traumatic events that affect entire communities, such as wildfires or hurricanes.

Faculty research at VCU

Over the next two weeks, we are publishing a series of stories demonstrating the wide diversity of faculty research at VCU, where inquiry, creativity and innovation are synonymous with public impact research. On Oct. 20, President Michael Rao, Ph.D., and Vice President of Research and Innovation P. Srirama Rao, Ph.D., will discuss a bold and ambitious new research strategic plan that will serve as a framework to streamline future investments, leading to increased funding and growth, ultimately advancing excellence in research at the university. Please visit the OVPRI website for event details on how you can participate in the conversation.

“When we think of resource allocation in the wake of a mass trauma, it’s not a one-size-fits-all approach,” Amstadter said. “If we knew individuals’ additive genetic risk in addition to psychological factors, such as social support, personality and coping resources, and socio-environmental variables, such as income level, access to secure transportation, jobs and financial security, all of those factors together could help us understand who is going to need immediate services that might help prevent future mental health issues versus who we need to just take a watchful waiting approach with versus who we’re pretty sure is going to be perfectly fine.”

Amstadter also hopes that by identifying underlying genetic mechanisms, trauma researchers can help break down the stigmas surrounding mental health.

“I think understanding genetics can decrease stigma for mental health problems because we can take out the feelings or thoughts of weakness. It helps people understand that they’re in part responding in the way that they’re biologically embedded to and that there are things they can do about that,” Amstadter said. “We can’t modify our DNA, but we can exert influence over our environment.”

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