Last week, I wrote that extreme stress can shrink certain parts of the brain, namely the hippocampus, and that the shrinkage helps to explain flashbacks and other symptoms of post-traumatic stress disorder.
But post-traumatic stress is a strange, mutable disorder with a confusing variety of symptoms and almost as many physical seats. Not everyone suffers from it. In fact, most people can survive serious trauma without crippling aftereffects. But the aftereffects in the others are real, and they may be inherited.
The hippocampus is one seat of the problem, but scientists have also noticed effects on the epigenome, the complex of molecules wrapped in and around a gene thread that affects which genes are expressed. It’s a flexible system that responds to the environment. Two people hardwired for the same trait might not show the trait in the same way because they have epigenetic differences that mute or emphasize the genes.
The epigenome happens to be pretty important in controlling stress hormones, including cortisol, which is released by the adrenal gland when the brain and body react to danger. In 2007, a study by Rachel Yehuda and her colleagues at the Mt. Sinai School of Medicine found that levels of cortisol were significantly different from ordinary populations among Holocaust survivors — and among their children. They tested adult children of survivors who did have PTSD, adult children of survivors who didn’t and a control group.
“Offspring with parental PTSD displayed lower mean cortisol levels,” the study found, and low cortisol is considered a risk factor for developing PTSD. That means parents with PTSD can pass on to their kids a predisposition for it.
Dietmar Spengler and Chris Murgatroyd at the Max Planck Institute for Psychiatry in 2009 found that stress in young mice caused by early separation from their mothers left a profound and lasting epigenetic change, also involving levels of stress hormones. The mouse’s epigenome “remembered” the stress and set patterns of behavior — including memory problems — that lasted a lifetime.
“The whole process results in behavioral changes,” said Ulrike Schmidt, who runs the lab at the Max Planck Institute and has reviewed the recent science in a study of her own. She says the epigenetic changes in lab mice are not just semi-permanent but also semi-inheritable — through the epigenome itself.
“At least in rodents, [the hormonal process] can be passed along, in part, to their offspring,” she says. “This means that traumatic experiences can cause changes across generations. I think it’s an exciting discovery.”
Cortisol, moreover, acts on the hippocampus, so the large amounts of cortisol squeezed into the blood during an intense or long-lasting trauma can also explain hippocampal shrinkage. “There are receptors for cortisol in the hippocampus,” McGill University psychiatry professor Sonia Lupien told her university magazine in 2002. “Long-term exposure to [stress] hormones can cause atrophy of the hippocampus, leading to memory impairment.”
A comprehensive PTSD drug would be the holy grail, of course. But that’s not in sight yet, says Schmidt. “We don’t understand the disorder well enough. These are just pieces of the puzzle.”