Mining the Interactions Among Genes, Experiences, and the Environment to Improve Mental Health

By Carol Gerwin

Deep inside the lab of Jordan W. Smoller, M.D., Sc.D., at Massachusetts General Hospital (MGH), a robotic arm reaches out to a plate of DNA samples, extracts hundreds of tiny portions, and spots them onto a computer chip. A laser fires and converts each speck into orange, green, and blue shapes that pop up on a nearby monitor.

Where most people see just clusters of colored dots, Smoller, a psychiatric geneticist and an affiliated faculty member of the Center on the Developing Child, sees genotypes—and powerful potential for mitigating some of the world’s most pressing public mental health problems, from autism and anxiety disorders to Alzheimer’s disease.

In his clinical practice, Smoller, a professor of psychiatry at Harvard Medical School and professor in the department of epidemiology at the Harvard School of Public Health, treats patients who are struggling with major depression, anxiety disorders, bipolar disorder, and other psychiatric conditions. Identifying the role of genes and experience in patients’ risk for developing these illnesses has been the focus of his research career. Smoller is also the director of psychiatric genetics and the associate vice chair of MGH’s psychiatry department.

Developing Treatment—and Prevention—Strategies

As science has moved beyond the question of nature vs. nurture, Smoller and his colleagues at the hospital’s psychiatric and neurodevelopmental genetics unit of the Center for Human Genetic Research are at the forefront of efforts to determine the complex interplay of genes, experiences, and the environment in mental health development. One of their largest studies is comparing DNA samples and brain images of more than 3,000 people with and without mental health difficulties. They hope to be able to start answering how the brain’s basic systems and circuits can be disturbed in different ways at different times that predispose some people to mental illness while leaving others more resilient.

Smoller notes that the major treatments for most psychiatric disorders today are based on insights suggested half a century ago and were developed by trial and error. But, he says, substantial advances over the last decade can change that.

smoller-block-quote.gif“We don’t yet understand exactly the ingredients that lead to various psychiatric disorders. This is an enormously complicated area,” he explains. “But as [research] tools are progressing, we are in a better position to look at how genes and experiences contribute to mood disorders and other disorders that cause people a great deal of suffering.”

For the first time, he says, research “offers a window into something potentially much more powerful as a tool for developing treatment and prevention strategies.”

Catalyzing Collaboration and Envisioning Breakthroughs

As part of his engagement with the Center, Smoller chairs the Science of Adversity and Resilience (SAR) monthly meeting series. One of several SAR activities, this series brings together an invited group of investigators at Harvard who represent a wide range of biological and social sciences. To stimulate cross-disciplinary conversation, guest presenters each month share their work on a selected topic. The forum is intended to spur fresh thinking among faculty members who may not have worked together previously and to foster new research collaborations.

“We hope to catalyze the enormous universe of research on child development that’s going on across Harvard—at the Medical School, the Faculty of Arts and Sciences, the School of Education, the School of Public Health, and all of the other elements of the University,” Smoller says. “It’s a remarkable community of researchers, some of whom have not had an opportunity to engage in interdisciplinary exchange, and we want to build together a shared foundation of research that can create a much more sophisticated understanding of development.”

Although Smoller has been at Harvard since his undergraduate years, he says he is surprised (and thrilled) to discover every few weeks another Harvard researcher whose work is central to his own and to the mission of the Center.

Indeed, Smoller has been inspired by the work of fellow Center-affiliated faculty member Takao Hensch, Ph.D., who has identified “sensitive periods” of development, when brain plasticity—the openness to influence by experiences—sharply increases in different areas. As a result, Smoller envisions the creation of a detailed developmental timetable and a corresponding map of the brain. Describing the relationship of each part of the brain to the world around it would enable public policy to target prevention and intervention to the brain’s timetable.

For example, intensive treatment at the precise times that children are developing the brain circuitry for executive function or attachment could yield superior results and be far more cost-effective than intervening at other times.

“If we can mobilize and capitalize on what’s already going on in these diverse fields, that would be tremendous,” Smoller says. “If we can then take that and catalyze new research and new interaction that crosses disciplines, we’ll really have something special.”

Carol Gerwin, a freelance writer and editor specializing in education and child development, is based in Newton, Mass.

Photo by Fred Field

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