MGH researchers are using computing power and collaboration across disciplines to study the roles biology and experience play in causing mental illness.

Not long ago, experts thought they knew the cause of most mental illness. “They blamed bad parenting,” says Jordan Smoller, MD, ScD, director of the Psychiatric and Neurodevelopment Genetics Unit in Mass General’s Department of Psychiatry. “It was a simple idea but it was just wrong.”

The long-debated question of whether “nature or nurture” causes mental illness has now been set aside in favor of a new understanding that both biology and human experience play interlocking roles.

Today, a more complex understanding is emerging through the efforts of researchers like Dr. Smoller, who takes a multidisciplinary approach from the fields of medicine, genetics and epidemiology (the study of large populations). He is working with colleagues to weave together the many threads that lead to the cause of mental illness.

This breadth of expertise and experience is just one example of how the Mass General Department of Psychiatry is working across research disciplines to combine basic scientific inquiry with patient care to help understand the roots of mental illness and alleviate suffering for those affected.

Seeking New Treatments for Mental Illness

The long-debated question of whether “nature or nurture” causes mental illness has now been set aside in favor of a new understanding that both biology and human experience play interlocking roles.

The Other Side of Normal by Jordan Smoller
Jordan Smoller, MD, ScD, writes about the causes of mental illness in his new book.

“The pace of research is really accelerating now,” says Dr. Smoller who describes these concepts in clear and readable language in his new book, “The Other Side of Normal.”

The combination of vast computing power and collaboration across scientific disciplines is producing many clues in the search for explanations. For example, more than 100 genetic variations have been identified that contribute to the development of schizophrenia, which affects about 2.4 million Americans. Other variations have been found in autism, bipolar disorder, depression and other conditions. “All of these diseases are polygenic,” meaning that multiple genes are involved, Dr. Smoller explains.

And many of the major mental illnesses turn out to be more genetically related than previously known. Knowing the genetic biology of a disease can point the way toward new targeted drug therapies that are far more specific to the disease than are today’s drugs.

At the same time that researchers are discovering new genes, they are also finding that human experience, particularly early in a child’s life, plays a parallel role in the cause of mental illness. “We are now learning how biology affects the way we experience life and, remarkably, how our experiences actually can change our biology,” Dr. Smoller says.

“We are now learning how biology affects the way we experience life and, remarkably, how our experiences actually can change our biology,”

For example, children who begin life in extremely adverse circumstances, such as neglect or abuse, are at risk for developing mental illness later in life. It’s partly a matter of timing. Adversity during certain times may affect the biology of the developing brain, forming new or different neuronal pathways in the brain that shape the way a person responds to life experiences in the future. There are “windows of vulnerability,” he says, during which changes in the brain circuits can have long-term consequences. For example, he says, “There is evidence from animal studies that such adversities may affect gene expression and set the course for how we respond to stress later in life.”

Motivated by Family History

Dr. Smoller says he has seen how adversity in early life is not necessarily a prescription for mental illness. As a girl, his mother was a refugee from Poland during World War II. She eventually came to the United States, earned her doctorate and became one of the leaders of the Women’s Health Initiative, a groundbreaking research study. His mother, Sylvia Wassertheil-Smoller, PhD, “came here not speaking a word of English,” Dr. Smoller says. “Then my father died when I was six, and she raised me by herself. She faced a tremendous amount of adversity and had a remarkable resilience.”

“Psychiatric illness accounts for more disability than heart disease and cancer combined.”

That family background led Dr. Smoller to focus on studying the science of the mind. Psychiatric illness accounts for more disability than heart disease and cancer combined, he notes. “Everyone has had someone in their family or someone close to them who has struggled with psychiatric issues,” Dr. Smoller says. “It’s an immensely important public health problem because of the suffering and pain these disorders can cause.”

But with government funding scarce, it’s difficult to move ahead with the research. “There are so many things we could be doing but we get stuck from lack of funding,” he says. The key, Dr. Smoller adds, is to understand how the normal brain works and how it can go awry and to apply that knowledge toward developing treatments that will help improve lives of people with mental illness.

You can help support this research by giving to The Psychiatric Genetics Fund.