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In the long-debated question of nature versus nurture, the emerging field of behavioral epigenetics may hold significant insight, suggesting that nature responds to the effects of nurture. 

Behavioral epigenetics examines the effects of the environment on genes that influence behavior. Research by several faculty members and graduates suggests exposure in the uterus or early childhood to negative environmental factors, such as stress and drugs, changes gene expression and causes problematic behavior.

Behavioral epigenetics is particularly exciting because of its interdisciplinary nature, said Barry Lester, professor of psychiatry and human behavior and pediatrics and director of the Brown Center for the Study of Children at Risk at the Alpert Medical School and Women and Infants Hospital. The field brings together molecular biologists, developmental psychologists, physicians, neuroscientists and other experts who do not usually interact. These interactions are "creating a new discipline that has the potential to uncover some really important findings," Lester said.

Behavioral epigenetics is a subset of the larger field of epigenetics, which has been the subject of growing interest over the past decade in part due to the Human Genome Project, said Audrey Tyrka, assistant professor of psychiatry and human behavior at the Med School. The sequencing of the human genome suggests humans are not that genetically different from chimpanzees or even roundworms. The key lies in epigenetic mechanisms, which turn different genes on and off in different species and cells without changing the genes themselves. Animal studies suggest that changes in gene expression are both heritable and reversible. 

In a recently published paper, Tyrka studied the effects of childhood adversity, including maltreatment and parental loss, on stress and risk for mental illness. This preliminary study suggested childhood adversity may cause changes in stress response due to epigenetic changes, Tyrka said.

Previous research in rats had suggested that when pups are in a negative environment — such as receiving less motherly care — a specific epigenetic mechanism kicks in. This mechanism is methylation, inhibiting the expression of a gene that regulates cortisol ­— a hormone that controls the stress response. As a result, the pups showed more extreme responses to stress.

Tyrka's study looked at cortisol responses in healthy adults with histories of childhood adversity. Tyrka found a link between childhood adversity and increased methylation, though she said it is difficult to say for sure the cortisol regulation gene is at fault, as there is no access to subjects' brains.

Both Lester and Tyrka agree the inaccessibility of the brain is a challenge in studying behavior-related epigenetic changes in humans. They depend on other specimens, such as saliva, blood and placenta to indirectly study the changes. 

In his research, Lester examines genes in the placenta to determine the adverse effects of a pregnant mother's exposure to negative environmental factors — such as stress, drugs and depression — on fetal development.

"This is a dream to be able to go back and actually untangle how this whole process potentially unfolds, " Lester said.

While at Brown, Cailey Bromer '11 worked with Lester on studying genes in the placenta regulating maternal cortisol, including the same gene Tyrka studied. 

Changes in the activation of these two genes due to negative environmental factors overexpose the fetus to cortisol, affecting fetal development, therefore putting the child at risk for behavioral and cognitive problems. Bromer will be publishing a paper on her work with Lester in the near future. 

Behavioral epigenetic findings have long-term implications for determining and helping "at-risk" individuals.

"When we establish that stressful environments have an effect on your genome, it becomes much more compelling to make environments better," Tyrka said. In addition to preventive measures addressing environments where adversity may occur, treatments targeting epigenetic changes may be developed. For example, Lester suggested treatments that may, in the future, inhibit addiction genes in the children of drug addicts.

Additionally, it is unknown whether stress interventions such as psychotherapy, medication, mindfulness and yoga may affect, or even reverse, the effects of negative environmental factors on gene expression.

While the argument of nature versus nurture rages on, developments in the field of epigenetics, particularly behavioral epigenetics, have implications for better understanding the underlying mechanisms of gene-environment interactions. 

"We're hopeful, and probably, when it comes down to it, everything that happens in our body is actually about gene expression," Tyrka said.




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