We can make susceptible mice resilient by blocking or inducing epigenetic modifications to certain genes or by altering the expression patterns of those genes to mimic the epigenetic tweaks. Likewise, epigenetic modifications and gene expression can be altered in resilient mice to make them more susceptible.
Other groups have found similar epigenetic alterations that last a lifetime. For instance, rat pups that are rarely licked and groomed by their mothers are more susceptible to stress later in life than are pups with more diligent carers. They are less adventurous than better-cared-for offspring and put up less of a fight in unpleasant situations (such as being placed in a beaker of water). Moreover, the females are less nurturing towards their own offspring. Epigenetic modifications seem to occur at several genes in the hippocampus in response to how much grooming young rats receive, and these alterations persist into adulthood.
These findings are likely to hold up in humans. For example, researchers have found that the genes identified in the rat-grooming studies were more methylated in the hippocampi of suicide victims who had experienced trauma as children than in the those of people who had died from suicide or natural causes and whose childhoods were normal. Likewise, our findings in mice given cocaine mirror epidemiological studies from the past few decades that have linked drug abuse, obesity and conditions such as multiple sclerosis, diabetes and heart disease to increased susceptibility to stress in humans.
More controversial is whether animals inherit epigenetic vulnerability to stress. According to this notion, epigenetic modifications in sperm or eggs drive aberrant patterns of gene expression in the next generation. Several groups have reported that male mice exposed to stress — by being removed from their mothers as pups or exposed to more aggressive mice as adults, for example — produce offspring that are more vulnerable to stress.
A mechanism is still elusive. Exposure to stress could somehow corrupt the male mouse's behaviour or affect some signalling molecule in his semen such that his partner alters her care for their young. Another possibility is that stress-linked epigenetic 'marks' in the sperm affect the development of offspring. No causal evidence yet links epigenetic changes in sperm to altered behaviour in offspring.