Two-time NARSAD Grantee, Kerry Ressler, M.D., Ph.D., co-authored a paper from a study done with a postdoctoral fellow in his lab at Emory University, Brian G. Dias, Ph.D., that suggests that sensitivity to certain fearful experiences may be passed down biologically from one generation to the next. The authors believe that a similar phenomenon could take place in humans, which could have implications for anxiety and addiction. Their findings were published online December 1st in Nature Neuroscience.
Dr. Ressler is a neurobiologist and psychiatrist and became interested in what is called “epigenetic” inheritance after working with at-risk populations where cycles of drug addiction, neuropsychiatric illness and other problems often seem to recur in parents and their children. Epigenetics refers to environmental impacts that alter gene expression without altering the underlying DNA sequence.
To study biological inheritance, Drs. Ressler and Dias worked with animal mouse models and focused on the mouse olfactory system, a system frequently studied that has a good existing mapping of brain circuits that process smell. They trained mice to fear the scent of a chemical, acetophenone, by giving the mice small electric shocks as the scent was wafted in their chamber. Eventually the mice learned to associate the scent with pain, with an increased startle response in the presence of acetophenone even without a shock.
To the researchers' surprise, when the mice were bred and gave birth, their pups exhibited increased sensitivity to the smell of acetophenone, startling more markedly to the smell compared to descendants of mice that had not gone through such conditioning. Additionally, a third generation of mice also inherited the reaction.
The researchers noticed significant changes in the brain of these mice as well. The mice sensitized to the acetophenone, as well as their offspring, had more neurons that produce a receptor protein known to detect the odor compared with control mice and their descendants. They also noticed that structures that receive signals from these specific neurons (which also send smell signals to other parts of the brain, including those that involve processing fears) were bigger. These effects were seen in mice conceived through in vitro fertilization as well.
Humans may inherit epigenetic alterations that influence behavior, too, Dr. Ressler suspects. A parent’s anxiety, he speculates, could influence later generations through epigenetic modifications of receptor genes for stress hormones. But Drs. Ressler and Dias are not sure how to prove the case, and do not wish to speculate beyond the current data in this mouse model for the time being.
The researchers acknowledge that they can’t be certain it’s the fear of the scent and not just a heightened sensitivity to the scent that is inherited. Skepticism that the inheritance mechanism is real will likely persist, Dr. Ressler says, “until someone can really explain it in a molecular way. Unfortunately, it’s probably going to be complicated and it’s probably going to take a while.”
For now, Drs. Dias and Ressler want to know: if the trained mice un-learn the fear of acetophenone (which can be done by repeated exposures to the smell without a shock) and then reproduce, will their children still have an increased sensitivity to it? “We think this type of result might have important implications for the treatment of adults with PTSD in preventing the intergenerational cycles of risk.”