Could Events in Our Parents’ Lives Affect Our Genome?

Could events in our parents’ lives have an impact on our own, not just in terms of social influence, but via direct effects on our genomes, a phenomenon known as ‘epigenetics’?

Epigenetic studies are revealing that the DNA ‘recipe’ for each organism appears far more responsive to the environment than previously thought, both to changes in the cellular environment, and to those outside the organism. And instead of DNA being seen as the sole controller of cellular function, there is now growing recognition that RNA – DNA’s chemical cousin – plays a key role. Moreover, the genome is increasingly viewed as a complex 3D entity, with dynamic interactions between genes and their control elements. These new ways of looking at the genome have important implications for our understanding of how the human brain works, and of some of the factors that might make it unique aming those of other species.

A dramatic illustration of how epigenetic mechanisms might be involved in mental disorders being passed down through the generations has come from a study led by Tracy Bale of the University of Pennsylvania. The study found that anxiety induced in male baby mice by exposing them to stressful stimuli – such as fox odour, restraint in a conical tube, and white noise – was passed down to future generations. Bale's team showed that the anxiety is transmitted to the offspring of the stressed mice through specific micro RNAs – molecules that regulate whether certain genes are switched on or off. Not only were nine specific micro RNAs found at higher levels in the sperm of the stressed male mice, but injection of purified forms of these micro RNAs into a fertilized mouse egg generated from unstressed parent mice led to the birth of anxious mice in the next generation.

A further study by Bale’s team showed that stress causes an increase of the hormone cortisol in the blood, which triggers the release of stress-inducing micro RNAs from a structure called the epididymis in which sperm are stored after production by the testicles. In an inter-generational feedback loop, the micro RNAs transmitted to the next generation affect genes that regulate blood cortisol in that generation. Bale hopes that having identified ‘signals’ that carry stress to future generations, it will now be possible to study ‘how would you reverse those signals, how dynamic are the cells to this environment ... and how the interaction of mom's and dad's genes affects [the transmission of stress].'

Of course, people are not mice. And an obvious obstacle in trying to study whether similar molecular mechanisms transmit anxiety across generations in our species is that it would hardly be ethical to induce stress in human baby boys and then see if this is transmitted to the next generation. So investigations of the role of epigenetic mechanisms, acting across generations as a possible factor in the genesis of human mental disorders, have had to focus on individuals who have been exposed to extremely stressful situations, and then assess what might be different about their epigenomes and those of their children, compared to unaffected individuals and their offspring.

Undoubtedly, the most horrific event in the 20th-century was the Holocaust of World War II, in which the Nazis murdered as many as 15 million people – mainly Jews, but also Slavs, gypsies, LGBT+ individuals, the disabled, and political opponents – in concentration camps across Germany and occupied Poland. Those who survived were deeply traumatised, resulting in an increased incidence of anxious and depressed individuals among the survivors. But it has been claimed that Holocaust survivors’ children are also more likely to develop post-traumatic stress disorder, depression, and anxiety, despite having grown up in a less-stressful environment.

What's more, a study led by Rachel Yehuda at the Icahn School of Medicine at Mount Sinai in New York has claimed to have found evidence that this apparent higher incidence of mental disorder is associated with epigenetic differences in the DNA of Holocaust survivors’ children. In particular, Yehuda claims that the children of male Holocaust survivors who suffered post-traumatic stress disorder had higher methylation of a gene involved in the stress response. Such methylation changes can affect the degree to which a gene is turned on or off. According to Yehuda, ‘the gene changes in the children could only be attributed to Holocaust exposure in the parents.’

Subsequently, though, Yehuda’s findings and conclusions, have come in for criticism from various directions. One criticism is that only a small number of individuals – 32 survivors and 22 of their offspring – were studied. Another potential flaw is that the study did not consider the possibility that survivors might – deliberately or inadvertently – have communicated the horror of their experience to their children while the latter were growing up, thereby exposing them to stress. As Josie Glausiusz, a participant in Yehuda’s study, and whose father survived the Bergen-Belsen concentration camp, has put it, ‘I was troubled by a question: How does one separate the impact of horrific stories heard in childhood from the influence of epigenetics?’

There has also been criticism of the fact that the study only investigated a small number of genes, and only found a small amount of change in the methylation states of the genes studied. Reflecting such concerns, John Greally, a geneticist at the Albert Einstein College of Medicine in New York, has noted that ‘the story being told by the Holocaust study is indeed fascinating as a scientific possibility, and will no doubt prompt others to pursue similar studies. Unfortunately, the story is typical of many in the field of epigenetics, with conclusions drawn based on uninterpretable studies.’

Claims about the role of epigenetic influences in the genesis of mental disorders in humans will always need to be scrutinized carefully, and with consideration of potential alternative explanations. Nevertheless, the increasing number of robust findings emerging from animal studies means that we should pay attention to the possibility that social influences might have impacts reaching beyond the individuals exposed to them.