Can trauma be inherited through genes?

Can trauma be inherited through genes?

Emerging science suggests that the effects of trauma—from war and genocide to abuse and environmental factors—could be genetically passed down from one generation to another.

Epigenetics is the study of how genes are turned off and on. The molecular process, known as gene expression, boosts the activity of some genes and quiets others by adding and removing chemical tags—called methyl groups—to genes. Multiple research studies have suggested that this may be a mechanism through which a parent’s trauma could be imprinted in the genes of offspring, and the epigenetic effects could be multi-generational.

The field “touches on all the questions that humanity has asked since it was walking on this planet,” says Moshe Szyf, a professor of pharmacology at McGill University. “How much of our destiny is predetermined? How much of it do we control?”                                                                                    

For some people, the concept that we can carry a legacy of trauma makes sense because it validates their sense that they are more than the sum of their experiences.

“If you feel you have been affected by a very traumatic, difficult, life-altering experience that your mother or father has had, there’s something to that,” says Rachel Yehuda, professor of psychiatry and neuroscience of trauma at Mount Sinai in New York. Her research points to a small epigenetic “signal” that a life-altering experience “doesn’t just die with you,” she says. “It has a life of its own afterwards in some form.” 

To understand how emotional trauma can transcend generations, consider the distinction between the genome—the body’s full complement of DNA—and the epigenome. Isabelle Mansuy, professor in neuroepigenetics at the University of Zürich, likens it to the difference between hardware and software. You need the genome “hardware” to function. But it is epigenetic “software” that instructs how genes in the genome should behave.

“All the time, in every cell, every moment, the epigenome is changing,” Mansuy says. It responds to all sorts of environmental factors, from chemical exposures to nutritional deficiencies. The epigenome determines which genes will be activated at a given time and which will remain silent.

Mental health in the generation after trauma

Yehuda uncovered an epigenetic mark in Holocaust survivors and their offspring, a group at greater risk for mental health challenges. She assessed 32 survivors and their adult children in 2015, examining the FKBP5 gene—which has been linked to anxiety and other mental health concerns.                                           

By extracting DNA from blood samples, the team identified epigenetic changes in the same region of the gene in the survivors and their children; but those alterations were not present in the DNA of a small group of Jewish parents and their offspring who lived outside of Europe and didn’t experience the Holocaust.

In a subsequent study published in 2020, Yehuda examined a larger cohort of subjects, looking at variables such as the sex and age of the parent during the Holocaust. She examined DNA methylation, one of the methods the epigenome uses to activate or quiet genes. DNA methylation generally adds a chemical mark to DNA; demethylation removes it.

Yehuda found that there were lower levels of DNA methylation in the FKBP5 gene in children whose mothers survived the Holocaust than in Jewish control subjects whose parents didn’t experience the Holocaust. Some studies have linked reduced DNA methylation in the FKBP5 gene to increased risk of disorders in adults such as PTSD. The results suggested that a mother’s trauma—even if it occurred during childhood—might lead to epigenetic changes within the DNA in her eggs and thus impact the mental health of her children.

A 2019 study with male Vietnam war veterans from Australia provides additional clues about how trauma transcends generations.

Researchers searched for methylation differences in the DNA encapsulated in the sperm of veterans suffering from PTSD and compared it to DNA of those without the condition. Ten regions of DNA showed different methylation patterns in PTSD veterans compared to non-PTSD veterans. The changes were present in nine different associated with psychiatric disorders such as PTSD. 

The methylation patterns in the vets with PTSD were linked with mental health conditions diagnosed in the veterans’ children, according to the study. The findings identified a unique pattern of DNA changes which could be inherited, “especially those that are associated with the stress response,” says Divya Mehta, senior research fellow at Queensland University of Technology in Australia.

Trauma symptoms in parents and offspring

Given humans’ long  lifespan and length of time to produce offspring, it’s far easier for researchers to explore inherited trauma in mice or rats, which produce multiple litters a year. In a series of experiments to understand how animals might transmit information about an ancestral trauma to their offspring, Brian Dias, associate professor in the University of Southern California’s developmental neuroscience and neurogenetics program, exposed mice to a chemical that smelled like cherry blossoms and paired that scent exposure with a mild electric shock.

The mice, naturally, learned to fear the odor. The next two generations of mice startled when they smelled the scent though they had never been exposed to it before. Dias later repeated the experiment with another chemical that smelled like almonds. This time, a subgroup of mice experienced the combination of odor and shock; later they were exposed to the odor without the shock. Over time, these mice no longer interpreted the odor as a threat. Their offspring didn’t fear the odor, either.

“Inheritance” does not mean the children will always show the same signs of trauma as the parent. In several studies, University of Zürich’s Mansuy has investigated epigenetic effects caused by the separation of mice mothers and their pups; with the mothers also exposed to stressors during the separations.

How could a stressful environment such as separation from the mother set off epigenetic changes in pups? We don’t know exactly, Mansuy acknowledges. The mechanism linking stress and the epigenome in brain and other cells “is not well understood.”

Still, the study found that the pups and their descendants exhibited depression, memory deficits, and risk-taking behaviors, such as an inability to evaluate potential dangers, among many behavioral changes. While the depression and memory decline extended to the third generation, the risk-taking started to diminish only after the fifth generation.

“It’s remarkable that some of the symptoms stay for so long,” Mansuy says. When the symptoms lessened, Mansuy found that the DNA methylation was altered in the male offspring’s sperm and brain.

Trauma from environmental causes

Trauma extends beyond devastating events such as child abuse or war. An insult to DNA can also be triggered through environmental causes.

One early study in 2005 investigated whether exposure to the agricultural fungicide vinclozolin could affect the sex of offspring in pregnant rats. It didn’t.

However, when the male offspring turned about a year old, researchers noticed that a high percentage of these animals’ sperm cells were dying. The same thing happened to the next three generations, though only the pregnant mothers had been exposed to vinclozolin.

It was the “first observation of non-genetic inheritance,” says Michael Skinner, study investigator and founding director of the Center for Reproductive Biology at Washington State University. Skinner and colleagues observed altered patterns of DNA methylation. “The sperm had an epigenetic shift and was carrying it to the next generation.”

Skinner later tested rats’ exposure to an herbicide called glyphosate. The chemical did not harm the rats’ offspring. But the third and fourth generation (the grandchildren and great-grandchildren) displayed a higher incidence of prostate, kidney, and ovarian disease, along with obesity and birth abnormalities. Examination of the sperm revealed alterations in the DNA methylation linked with higher incidence of disease.

The research suggested that though it skipped one generation, the effects of glyphosate passed epigenetically to future generations.

Reversing epigenetic changes

If these studies sound worrying, preliminary evidence suggests it may be possible to reverse some epigenetic changes. 

Mansuy and colleagues hypothesized that an enriched environment could lessen trauma-associated behavior. In several experiments, she placed adult mice that had been traumatized early in life into cages with many other mice, running wheels, toys, and a maze. Compared to traumatized mice in a standard enclosure, traumatized mice who then lived in the more stimulating setting didn’t show the symptoms of trauma behavior. Their offspring didn’t, either.

Mansuy saw differences in the glucocorticoid receptor gene, which helps regulate the body’s response to stress, between the mice who benefitted from enrichment and those that didn’t. The results suggested the epigenetic effects of trauma had been corrected. While the study examined only this gene, Mansuy has extended her studies to additional genes and expects to release new data soon.

Szyf found it was possible to reverse the effects of DNA methylation in rats who were anxious because of poor maternal care. Once they reached adulthood, he injected the rats with a drug—trichostatin A—and observed the mice showed fewer signs of stress and “started behaving like animals that were not subjected to this kind of early life adversity,” he says. The drug also caused DNA demethylation, or removal of tags, in the glucocorticoid receptor gene that Mansuy was studying.

Some research suggests that even exercise can influence the epigenome. Skinner studied 70 pairs of identical human twins who agreed to have their level of exercise monitored. The more physically active twins experienced lower rates of obesity and metabolic disease. Their epigenome also changed. The twins who exercised more had chemical tags on their genes linked to lower metabolic syndrome.

“All environmental factors, from toxicants to diet to exercise to climate change” impact health through epigenetics, Skinner says.

Coping with adversity                                               

While it’s easy to focus on the negative aspects of potentially inheriting the effects of trauma, epigenetic changes also may help future generations by activating genes to help offspring cope with adversity.

“That’s what I think happens,” Yehuda says. “But it depends. If you’re not living in adversity, you might become hypervigilant. And if you’re living in adversity, you might have a skill set to survive it that is honed from life lessons of the past somehow.”

With the rise of technologies such as next generation sequencing that allow researchers to analyze types of cells and how they respond to stressors, “we’re now in a gilded age” of exploration, according to Dias. His current research explores how many sperm are marked before the effects of trauma are transmitted, how enduring these marks are, and how embryos may bear imprints of a trauma.

How we might inherit the effects of our parents’ or ancestors’ traumas is a story that is just starting to be told. Some scientists are not convinced by the evidence so far.

“I don’t think any studies have met the standard of proof to say that this is plausibly happening in mammals,” says John Greally, chief of genomics and professor of genetics at Albert Einstein College of Medicine in New York. He worries these studies actually “worsen the damage” because they can make people from communities with multi-generational trauma, such as Native Americans, “feel like they are intrinsically damaged and there’s nothing they can do about it,” while distracting from ways to address the real-world causes of traumas.

Other critics have observed that many DNA methylation marks on genes are removed when human sperm and egg unite. There are research papers, Dias notes, which showed some genes come through that process with marks intact. Still, he’s among those who agree more work needs to be done to demonstrate the transmission mechanisms.

What’s clear is that humankind has learned to navigate the effects of traumas, inherited or not, or we wouldn’t still exist. Resilience is the more dominant trait, Szyf says, “otherwise we would not survive as a race.”

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