Epigenetics and Historical Trauma

Haunted by History

For those caught in history’s churn, the result can be psychiatric symptoms and chronic disease caused by stress. Because these cellular changes are said to be made not at the level of the genetic code, but ‘above’ the genome – through the molecules that control gene expression – they are called ‘epigenetic’.

Epigenetic trauma was found in children exposed in utero during the Dutch famine of 1944 to 1945, when Nazis stopped food from reaching populations in the Netherlands. As adults, the Hongerwinter babies exposed to stress in the womb turned out overweight with impaired glucose levels and increased cardiovascular risk, compared with unexposed siblings. The cause? A lack of ‘methyl groups’ at a number of key genes. These molecules act like ‘off’ switches by attaching to the DNA helix and stifling gene transcription. For the Hongerwinter babies, this hypomethylation led to the overproduction of certain proteins that affect growth and metabolism, triggering a cascade of cellular interactions that trended toward disease. While these epigenetic effects are uneven, the mode of transmission was surprisingly direct – stress from the mother impacted the gene expression of the developing foetus, greatly increasing the offspring’s disease risk.

Those findings apply to a single generation, yet they tug at the edges of evolutionary theory, in which species change slowly over millennia, not rapidly over the months or years of a single life. Charles Darwin’s process of natural selection holds that nature choses the best-adapted organisms to reproduce and survive in any given ecosystem. The process operates when DNA sequences mutate randomly, and organisms with the specific sequences best-adapted to the environment multiply and prevail – causing gene expression to shift. Yet as surely as the slow march of Darwinian evolution shapes life on Earth over aeons, scientists have found that epigenetic signals can work each day, and not just through methyl groups. Experience in the environment could also alter chromatin, the molecular matrix making up our chromosomes; RNA, the messenger molecules that translate genetic instructions from DNA into protein; and histones, the proteins involved in packaging and structuring the chromatin comprising the genes.

Some of the most important work in the field comes from the neuroendocrinologist and stress expert Bruce McEwen at Rockefeller University in New York, who has been studying epigenetic change caused by poverty, addiction and family violence. With his colleagues, he has found that such social stressors increase production of the adrenal stress hormone cortisol. That, in turn, retunes the genes in a brain structure called the hippocampus, degrading synapses between cells and compromising memory and mood. Stress also gets to the amygdala, the brain centre for fear, tweaking genes that expand the structure’s dendrites; the expanded amygdala generates a heightened sense of anxiety when more stress is afoot. Researchers from Duke University in North Carolina studied 132 impoverished adolescents, and found that the chronic stress of noise and violence increased methylation of a particular bit of DNA – the proximal-promoter region of the serotonin-transporter gene (SLC6A4) – indicating a heightened fight-or-flight response within their amygdala and a lower level of serotonin, associated with depression.

Epigenetic changes can occur during an individual’s lifetime or be induced by pregnant mothers when their stress hormones reach the womb. But can they be passed down the generations?

Yes, says Michael Skinner, an evolutionary biologist at Washington State University. He and colleagues report that ‘environmentally induced epigenetic transgenerational inheritance has now been observed in plants, insects, fish, birds, rodents, pigs and humans’. In rodents, such changes can last at least 10 generations and, in plants, hundreds.

In an extraordinary and disturbing series of experiments conducted over the course of years, Skinner has shown just how devastating epigenetic damage can be. To do his work, he exposed mice to a series of one-time environmental toxins, including the insect-repellent DEET, the plastic BPA (bisphenol A), the historic insecticide DDT, and hydrocarbons such as jet fuel and oil, during a key period of foetal development, when sex organs were forming in the womb. By the second generation and every generation thereafter without further exposure, he reports, male descendants had tumours, kidney disease, prostate disease, testicular disease and immune disease in very high frequencies. Four generations out, the effects seemed truly transgenerational: female descendants suffered ovarian failure, polycystic ovarian disease and premature puberty. The overwhelming majority of offspring were easily stressed, and many were obese. ‘Ninety per cent of the animals have multiple diseases,’ Skinner says. Without any further exposure, each toxin precipitated a unique biological fingerprint in the form of an altered epigenome, and a unique disease profile passed from one generation to the next.

Could this kind of phenomenon explain the Kelm rabbis’ early sudden deaths due to cardiovascular disease? Research in cardiology now traces atherosclerosis, vascular disease, arrhythmia, artery disease and even cardiac hypertrophy to epigenetic effects – in the individual. Testing whether we can extend such findings across generations will take more time. While exposure to maternal stress can alter a baby’s epigenome, the per cent of culture and biology that carries trauma forward, for humans is still unknown.

Haunted by History

WOW

What an article!