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.
Smoller, a professor of psychiatry at Harvard Medical School and an associate professor in the department of epidemiology at the Harvard School of Public Health, treats patients in his clinical practice who are struggling with major depression, anxiety disorders, bipolar disorder, and other psychiatric disorders. Identifying the role of genes and experience in patients’ risk for developing these disorders 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.
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’s intense interest in exploring the critical interaction of genes and environment has motivated his close involvement with the Center on the Developing Child. In early 2012, the Center named Smoller to be the first science director of its new Science of Health and Development Initiative to spur research and new ways of thinking that ultimately could inform innovations in public health policy and practice. The immediate goal is to create a hub for multi-disciplinary research on child development, drawing on the breadth and depth of expertise in diverse fields across the University.
Developing Treatment—and Prevention—Strategies
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 substantial advances over the last decade can change that, Smoller says.
“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 multiple levels of 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.”
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. In order to tap the University’s vast potential, Smoller hopes to entice colleagues to break out of their traditional academic silos and collaborate.
“With this Initiative, 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,” he 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.”
Smoller will work closely on the Initiative with an advisory group of scientists he likes to call his “dream team”: Center-affiliated Harvard faculty members Takao Hensch, Ph.D.; Charles A. Nelson, III, Ph.D.; David R. Williams, Ph.D., M.P.H.; and Michelle A. Williams, Sc.D.
Mapping the Brain To Target Public Policy
Initial plans for activities include establishing a program of seed funding for Harvard-based investigators; hosting renowned speakers with expertise in the science of health and development from across the country and around the world; supporting research projects in new areas of inquiry that bring together the biological and social sciences; and creating a forum where faculty members engaged in the Initiative can connect and provide feedback for one another, thereby fostering cross-disciplinary work.
The Initiative’s research will parallel the Center’s interest in advancing the scientific understanding of how genes, experience, and the environment interact during prenatal, child, and adolescent development to affect brain development and lifelong outcomes in health, learning, and behavior. But the Initiative will zero in on the biology of adversity and resilience; lifelong health disparities (including racial and social disparities); the impact of developmental periods on trajectories of mental and physical health; causal mechanisms that explain the origins of disparities in health, learning, and behavior; and the empirical evaluation of scientifically informed interventions on mental and physical health.
Inspired by the work of advisory board member Hensch, who has identified “sensitive periods” of development, when brain plasticity—the openness to influence by experiences—sharply increases in different areas, 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. Intensive treatment at the precise times that children are developing the brain circuitry for executive function or attachment, for example, 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 of the Initiative’s potential. “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