3. The second revolution: is stress hereditary?

The fact that important childhood trauma can change behavior practically for life implies that something has marked the individual’s development, if not independently then in a complementary manner to their genetics. That something is epigenetics, the series of hereditary changes from one cell to its daughters that don’t depend on the DNA sequence. But can epigenetic changes be passed on to our descendants? This question is still up for debate and cause for much skepticism, as it contradicts some of Darwin’s basic hypotheses, but some indications of this have come specifically from studying stress. Here are some of them.

The group led by Kerry Ressler, professor at Harvard Medical School, had been studying some of these issues for years. “It was complicated, but we started from the observation that child abuse tends to be perpetuated generation after generation,” he said. In 2014, one of his papers went around the world. In it, they used male mice trained to be afraid of a specific smell, acetophenone (similar to cherries). The revolution came when they discovered the first- and second-generation offspring of these mice were also afraid of this smell, but none of the other mice were. And it wasn’t a behavior they had learned: it even happened when the mice were born through in vitro fertilization of other mothers and kept in separate cages.

How could this happen? Their hypothesis was that during the training process, the epigenetics of the gene that detects that smell had been altered: it had lost some methylation marks (a group of chemicals stuck to the DNA) that kept it downregulated. In fact, this loss was also seen in the descendants of these mice. The enigma was, how did the change survive the reset these epigenetic marks experience at fertilization? “We don’t know,” Ressler admits. “For now, the mechanism is a great black box.”

Ressler’s group isn’t the only one studying these topics. Rachel Yehuda, professor of Psychiatry at Mount Sinai Hospital in New York, has been researching the possibility of posttraumatic stress being inheritable for years. She has published numerous articles on the consequences of the suffering experienced by holocaust survivors and their descendants. In these studies, she has shown that there is a persistent alteration in the hypothalamic–pituitary–adrenal axis that regulates response to stress both in those who experienced it directly and in their children, who are more depressed and anxious.

In any case, in interpreting these studies we must consider that there are many elements that could distort the results, like for example a more complicated family environment. To get more evidence, “We decided to study what happened to mothers who were pregnant on 9/11, during the attack on the Twin Towers,” explained Yehuda. The results showed that there was also an alteration in the axis, measured in cortisol levels in both mothers and babies at 7 months, particularly in those who had suffered posttraumatic stress.

Her latest research has also looked at the possible role of epigenetics. To do so, they studied methylation marks on the FKBP5 gene –one of the most studied marks in relation to stress- both in holocaust survivors and their adult children. The results show mutations in both groups, although there are subtle differences that will have to be confirmed in future studies.

This is one of the challenges still facing epigenetic studies: to understand the functional relevance of these mutations. Mathias Schmidt posed the question, “What is the threshold after which we can say they have a significant impact?”

And Isabelle Mansuy, professor at the Swiss Federal Institute of Technology Zurich answered, “There’s no magic number.”