Israel Rosenfield and Edward Ziff, The New York Review of Books:
As scientists came to better understand the function of methylation in altering gene expression, they realized that extreme environmental stress—the results of which had earlier seemed self-explanatory—could have additional biological effects on the organisms that suffered it. Experiments with laboratory animals have now shown that these outcomes are based on the transmission of acquired changes in genetic function. Childhood abuse, trauma, famine, and ethnic prejudice may, it turns out, have long-term consequences for the functioning of our genes.
Numerous clinical studies have shown that childhood trauma—arising from parental death or divorce, neglect, violence, abuse, lack of nutrition or shelter, or other stressful circumstances—can give rise to a variety of health problems in adults: heart disease, cancer, mood and dietary disorders, alcohol and drug abuse, infertility, suicidal behavior, learning deficits, and sleep disorders. Since the publication in 2003 of an influential paper by Rudolf Jaenisch and Adrian Bird, we have started to understand the genetic mechanisms that explain why this is the case. The body and the brain normally respond to danger and frightening experiences by releasing a hormone—a glucocorticoid—that controls stress. This hormone prepares us for various challenges by adjusting heart rate, energy production, and brain function; it binds to a protein called the glucocorticoid receptor in nerve cells of the brain.
Normally, this binding shuts off further glucocorticoid production, so that when one no longer perceives a danger, the stress response abates. However, as Gustavo Turecki and Michael Meaney note in a 2016 paper surveying more than a decade’s worth of findings about epigenetics, the gene for the receptor is inactive in people who have experienced childhood stress; as a result, they produce few receptors. Without receptors to bind to, glucocorticoids cannot shut off their own production, so the hormone keeps being released and the stress response continues, even after the threat has subsided.
It is now known that childhood stress can deactivate the receptor gene by an epigenetic mechanism—namely, by creating a physical barrier to the information for which the gene codes. What creates this barrier is DNA methylation, by which methyl groups known as methyl marks (composed of one carbon and three hydrogen atoms) are added to DNA. DNA methylation is long-lasting and keeps chromatin—the DNA-protein complex that makes up the chromosomes containing the genes—in a highly folded structure that blocks access to select genes by the gene expression machinery, effectively shutting the genes down. The long-term consequences are chronic inflammation, diabetes, heart disease, obesity, schizophrenia, and major depressive disorder.
Such epigenetic effects have been demonstrated in experiments with laboratory animals.
Experiments like these have shown that even animals not directly exposed to traumatic circumstances—those still in the womb when their parents were put under stress—can have blocked receptor genes. It is probably the transmission of glucocorticoids from mother to fetus via the placenta that alters the fetus in this way. In humans, prenatal stress affects each stage of the child’s maturation: for the fetus, a greater risk of preterm delivery, decreased birth weight, and miscarriage; in infancy, problems of temperament, attention, and mental development; in childhood, hyperactivity and emotional problems; and in adulthood, illnesses such as schizophrenia and depression.
Until the mid-1970s, no one suspected that the way in which the DNA was “read” could be altered by environmental factors, or that the nervous systems of people who grew up in stress-free environments would develop differently from those of people who did not. One’s development, it was thought, was guided only by one’s genetic makeup. As a result of epigenesis, a child deprived of nourishment may continue to crave and consume large amounts of food as an adult, even when he or she is being properly nourished, leading to obesity and diabetes. A child who loses a parent or is neglected or abused may have a genetic basis for experiencing anxiety and depression and possibly schizophrenia. Formerly, it had been widely believed that Darwinian evolutionary mechanisms—variation and natural selection—were the only means for introducing such long-lasting changes in brain function, a process that took place over generations. We now know that epigenetic mechanisms can do so as well, within the lifetime of a single person.
Whether epigenetic effects of stress can be transmitted over generations needs more research, both in humans and in laboratory animals. But recent comprehensive studies by several groups using advanced genetic techniques have indicated that epigenetic modifications are not restricted to the glucocorticoid receptor gene. They are much more extensive than had been realized, and their consequences for our development, health, and behavior may also be great.
It is as though nature employs epigenesis to make long-lasting adjustments to an individual’s genetic program to suit his or her personal circumstances, much as in Lamarck’s notion of “striving for perfection.” In this view, the ill health arising from famine or other forms of chronic, extreme stress would constitute an epigenetic miscalculation on the part of the nervous system. Because the brain prepares us for adult adversity that matches the level of stress we suffer in early life, psychological disease and ill health persist even when we move to an environment with a lower stress level.
Epigenetics has also made clear that the stress caused by war, prejudice, poverty, and other forms of childhood adversity may have consequences both for the persons affected and for their future—unborn—children, not only for social and economic reasons but also for biological ones.