VCU news

By Anne Dreyfuss
C. Kenneth and Dianne Wright Center for Clinical and Translational Research

Virginia Commonwealth University is part of an international research team that has received a Wellcome Trust grant totaling more than $5.7 million to uncover the underlying biological processes that cause major depressive disorder. The study, to be conducted by researchers from VCU, the University of Oxford and throughout China, is an extension of a study from the same team that uncovered the first identified risk genes for clinical depression last year.

The design of the five-year study will replicate and extend the original, with researchers conducting in-depth personal interviews with Han Chinese women who have had at least two episodes of major depression and have no history of alcohol or drug abuse. Researchers will also collect DNA samples from study participants. While the study’s design will follow the same structure of the original, it will be four times as large.

The first study recruited 6,000 cases of recurrent major depression and 6,000 controls, whereas the current study will recruit approximately 24,000 Han Chinese women with severe clinical depression and 24,000 controls. Together with the existing sample of 12,000, the total sample will be 60,000, which the researchers estimate is sufficient to identify at least 30 genetic risk loci. This will transform the scientific community’s understanding of the origins and nature of major depressive disorder, providing a starting point for improvement in mental health care.

“Our opportunity is to replicate the initial findings and to substantially enlarge the number of variants that we have found so that we may be in a better position to articulate distinct biological pathways to major depression,” said Kenneth S. Kendler, M.D., professor of psychiatry and human and molecular genetics at VCU School of Medicine. Kendler is a key collaborator on the study that is led by Jonathan Flint, M.D., professor, Wellcome Trust Centre for Human Genetics at the University of Oxford.

Major depression is one of the most common mental disorders in the U.S., according to the National Institute of Mental Health. In 2012, an estimated 16 million adults in the U.S. aged 18 or older had at least one major depressive episode in the past year, representing almost 7 percent of the population.

The second phase of the study will collect genetic information and high-quality phenotypes for major depressive disorder at an unprecedented scale. The aim of this phase of the study is to expand upon the initial findings so that the researchers can understand from a genetic, and ultimately neurobiological, perspective the origins of the second largest contributor to morbidity of any disease throughout the world.

“We have not been able to design better treatments for clinical depression because we don’t know what the cause is,” Kendler said, adding that current pharmacological treatments for the disease were all found in the 1950s using primitive animal models. “The ideal result of this study will be that of those 30 genes that we discover, many of them are in a single biological pathway. That would be like spotlights indicating ‘This is the biological pathway to clinical depression. That is where we should look to try to develop new treatments.’”