An Interplay of Genes and Environment

Couple Wins Two Large Prizes for Tracking Human Development

Research by partners Terrie Moffitt and Avshalom Caspi have open new means to understand how genes interact with our environment.

Duke University psychologists Terrie Moffitt and Avshalom Caspi, partners in research and in marriage, are being jointly recognized with the Klaus J. Jacobs Research Prize for Productive Youth Development at a Dec. 3 ceremony in Zurich. The prize includes a 1 million Swiss Franc award to further the couple's research.

On Oct. 29, they also are receiving the Ruane Prize for Outstanding Achievement in Child and Adolescent Psychiatric Research from NARSAD, the brain and behavior research fund. The $50,000 award recognizes the couple's international research exploring how the environment and genes interact to shape human behavior and mental health.

Their path-breaking work has been measuring human growth and development from childhood through adulthood and has shown that it isn't just genes or environment that shape a person, but rather the interactions between them.

"With heart disease and cancer, genetic researchers have always known to include factors like smoking and exercise. We wanted to do the same thing for the study of behavior," said Moffitt, the Knut Schmidt Nielsen Professor of Psychology and Neuroscience at Duke.

"Their work has had an enormous impact with respect to the interaction of genetic risk and environment, and on the prediction of adult psychiatric outcomes from childhood behavior patterns," said Dr. Judith L. Rapoport of the National Institute of Mental Health, who is also a NARSAD Scientific Council member and chair of the Ruane Prize selection committee. "This remarkable couple carries out their work in the United States, United Kingdom and New Zealand, where they are also training a new generation of investigators."

Combining detailed histories and psychological testing with genetic analysis, the couple's work relies mostly on two large, long-term studies. The Dunedin Longitudinal Study is following 1,000 people born in 1972 in New Zealand who are now 38 and have been interviewed and measured every two years. The Environmental-Risk Longitudinal Twin Study follows 1,100 British families with twins born in 1994-1995. They have been tracked from birth through todayand are entering adolescence.

These two study cohorts are treasure troves of data that Caspi and Moffitt have mined for genetic and environmental markers that might predict costly long-term mood disorders, antisocial and criminal behavior, psychosis and addiction.

"I think of the longitudinal studies as our scientific tool," Caspi said. "Other people have a microscope or a scanner to do their measurements. We bring in experts as needed to help us explore whatever questions we can in the data."

Since arriving at Duke in 2007, the pair have published studies on breast feeding and IQ, marijuana use and gum disease, early exposures to drugs or bullying leading to later conduct problems, pre-adolescent signs of psychotic disorders, and a replication of their work linking a particular genotype with a greater risk for long-term mood disorders in people who were exposed to psychological trauma in childhood.

"What's truly spectacular is that not only are they producing so much work, so much of it is so good," said developmental psychologist Laurence Steinberg of Temple University, last year's winner of the Jacobs Prize. "Lots of people have big data sets. It's their ideas that merit this award."

Early next year, Caspi and Moffitt will return to New Zealand for the next round of data collection on the Dunedin cohort. Each of the nearly 1,000 subjects will go through an 8-hour interview and testing, which this time also will include images of the subjects' retinas for a study on the vasculature system, which is being done with the Duke-NUS Medical School in Singapore.

"When you study people from birth to adulthood, by necessity you have to change what you study," Caspi said. "Puberty was fascinating, but now we're learning about cardiovascular disease."

As good as the longitudinal studies are, they are only observational, Caspi added. One can't randomly assign people to the condition of violence victimization to measure its effects. The researchers also can't go back and ask questions they wish they had included when the subjects were 7 years old, he said.

The Dunedin study was founded as a public health study to track the prevalence of various conditions. Moffitt first began working with it when the subjects were 11 and she began to probe the neuropsychology of conduct disorders. "The study subjects were just the right age," she said.

What she concluded, in part, was that most adolescents are only temporarily unmanageable, while others are on a life-long trajectory of violent and destructive behavior that stems from an interaction of their genes and family environment. This idea, first described in a 1993 paper, has had profound implications for psychology, criminology and the law.

Steinberg said Moffitt's findings on adolescent conduct disorders had direct bearing on two recent U.S. Supreme Court decisions abolishing the death penalty and sentences of life without parole for adolescent offenders.

"A lot of kids do bad things as adolescents and then grow up to be law-abiding adults," Steinberg said. "We really shouldn't leap to conclusions about the long-term prospects of a juvenile offender. Terrie's work on this has transformed the way the world thinks about adolescent crime and delinquency."

Neither one's genes nor one's childhood determine a life's course, Caspi said. It's the interactions that matter.

"The key point we want to make is that you can't choose your genes, but you face many choices in life which can determine how those genes will play out," Moffitt said.

Though a child doesn't have much control over an abusive household, Moffitt and Caspi's findings argue for schools and families to intervene forcefully on behalf of troubled kids early to prevent difficulties later on.

"An ounce of prevention truly is worth a pound of cure," Moffitt said.