Searching for answers to causes of childhood depression

Erin Dunn

February 1, 2012

Over the past decade, scientists have produced a flurry of studies exploring the role of genetic (nature) and environmental factors (nurture) in youth depression, but there has been little consensus on how depression is jointly impacted by specific genes and external factors, such as poverty, abuse, and negative family relationships.

The lack of a clear understanding of how genes and environments both contribute to childhood depression led Erin Dunn, postdoctoral research fellow and recent graduate of the Harvard School of Public Health (HSPH), and her colleagues to do a comprehensive review of studies that tested for gene-environment interaction in youth depression. Their goal was to systematically identify these studies, examine the methods used, and summarize findings to guide future studies. The review was published December, 2011 in the Journal of Child Psychology and Psychiatry (JCPP). Read the abstract.

Dunn, a former Richmond Fellow at the Center on the Developing Child at Harvard University, has had a longstanding interest in children’s mental health ever since teaching in early childhood and elementary school settings, where she saw students with a variety of mental health issues.

Journey to discovery

“When the Human Genome Project began we thought we were going to find all the genetic determinants of mental illness and other health problems we face. The journey to discover all those genes has been much more complicated than originally envisioned,” said Dunn, who is now a post-doctoral research fellow in the Psychiatric and Neurodevelopmental Genetics Unit in the Center for Human Genetic Research at Massachusetts General Hospital.

The Connecticut native led a study team that included HSPH researchers S V Subramanian, professor of population health and geography, Jordan Smoller, associate professor in epidemiology, and senior author Karestan Koenen, adjunct associate professor of society, human development, and health.

According to the National Institute of Mental Health, about 11% of adolescents have a depressive disorder by age 18. Girls are more likely than boys to experience depression. The risk for depression increases as a child gets older. The World Health Organization considers major depressive disorder the leading cause of disability among Americans age 15 to 44. Studies in twins show that between 30-80% of the variation in youth-onset depression is due to genes. Other contributors are environmental factors such as poverty, family relationships, divorce, or abuse.

“Getting depression early in life is particularly bad because depression tends to recur and can lead to a poor quality of life and poor social and work outcomes,” Dunn said. What intrigues her is that not all youth exposed to these environmental risk factors develop depression, raising questions about individual differences in genetic sensitivity to adverse environmental conditions.

A bird’s-eye view

To conduct the latest study, Dunn and her colleagues searched two major scientific literature databases of studies published between 2003 and March 2010. Of 278 articles on the subject, they identified 20 studies that tested for candidate gene-environment interaction in youth (up to age 26). In those, the researchers compared research design, samples studied, measures used, genes explored, and environmental factors studied.

While 16 of the 20 studies identified both genetic and environmental factors as increasing the risk of depression, the studies employed such a mix of methods, analyses, and measures that it was challenging to compare findings and assess “the strength of the evidence” for specific gene-environment interactions.

“Our study provides a bird’s-eye view of gaps in this field revealed in this literature review,” Dunn said. “We need to pump the brakes a bit and do a better job of doing more rigorous science,” she said. “The public health implication is that we can’t think solely in terms of genetics and environment—we have to think of both. The challenge for the field is to figure out the best strategies to do that.”

The researchers included 20 recommendations in the paper to guide future studies. Their guidelines include how to conceptualize, measure, analyze, and report genetic-environment interactions. “We wanted to develop a set of recommendations to move this exciting and powerful field forward,” Dunn said.

Funding for the study was provided by the Richmond Fellowship from the Center on the Developing Child at Harvard and the National Institute of Mental Health.

“Research Review: Gene-Environment Interaction Research in Youth Depression – A Systematic Review with Recommendations for Future Research,” Erin C. Dunn, Monica Uddin, S.V. Subramanian, Jordan W. Smoller, Sandro Galea, and Karestan C. Koenen. Journal of Child Psychology and Psychiatry, December 2011.

–Marge Dwyer

photo: Aubrey LaMedica