A person's experience as a child or teenager can have a profound impact on their future children's lives, new work is showing. Rachel Yehuda, a researcher in the growing field of epigenetics and the intergenerational effects of trauma, and her colleagues have long studied mass trauma survivors and their offspring. Their latest results reveal that descendants of people who survived the Holocaust have different stress hormone profiles than their peers, perhaps predisposing them to anxiety disorders.

Yehuda's team at the Icahn School of Medicine at Mount Sinai and the James J. Peters Veterans Affairs Medical Center in Bronx, N.Y., and others had previously established that survivors of the Holocaust have altered levels of circulating stress hormones compared with other Jewish adults of the same age. Survivors have lower levels of cortisol, a hormone that helps the body return to normal after trauma; those who suffered post-traumatic stress disorder (PTSD) have even lower levels.

It is not completely clear why survivors produce less cortisol, but Yehuda's team recently found that survivors also have low levels of an enzyme that breaks down cortisol. The adaptation makes sense: reducing enzyme activity keeps more free cortisol in the body, which allows the liver and kidneys to maximize stores of glucose and metabolic fuels—an optimal response to prolonged starvation and other threats. The younger the survivors were during World War II, the less of the enzyme they have as adults. This finding echoes the results of many other human epigenetic studies that show that the effects of certain experiences during childhood and adolescence are especially enduring in individuals and sometimes even across generations (right).

Most recently, a new study looked at the descendants of the Holocaust survivors. Like their parents, many have low levels of cortisol, particularly if their mothers had PTSD. Yet unlike their parents, they have higher than normal levels of the cortisol-busting enzyme. Yehuda and her colleagues theorize that this adaptation happened in utero. The enzyme is usually present in high levels in the placenta to protect the fetus from the mother's circulating cortisol. If pregnant survivors had low levels of the enzyme in the placenta, a greater amount of cortisol could make its way to the fetus, which would then develop high levels of the enzyme to protect itself.

Epigenetic changes often serve to biologically prepare offspring for an environment similar to that of the parents, Yehuda explains. In this case, however, the needs of the fetus seem to have trumped that goal. With low levels of cortisol and high levels of the enzyme that breaks it down, many descendants of Holocaust survivors would be ill adapted to survive starvation themselves. In fact, that stress hormone profile might make them more susceptible to PTSD (below, yellow); previous studies have indeed suggested that the offspring of Holocaust survivors are more vulnerable to the effects of stress and are more likely to experience symptoms of PTSD. These descendants may also be at risk for age-related metabolic syndromes, including obesity, hypertension and insulin resistance, particularly in an environment of plenty.

Yet it is still too early in our investigation into the epigenetics of this complex stress-response system to know for sure whether these molecular changes indicate any real-world risks or benefits. “If you are looking for it all to be logical and fall into place perfectly, it isn't going to yet,” Yehuda says. “We are just at the beginning of understanding this.”

Parent’s Struggle, Child’s Risk

A variety of studies, many using long-term medical records from large populations, have found that certain experiences affect future descendants' health risks. —Victoria Stern