Current Research Strategy

From its inception, HDRF’s goal has been to accelerate the development of new and better treatments for depression. The treatment of depression remains a great challenge. Recent studies have shown that only one third of people with depression recover in response to treatment with a single antidepressant and only another one-third recover after months and months, even with multiple treatment trials (STAR*D, Rush et al 2006.)

While the discovery of Prozac was a breakthrough in its time, in the over 25 years since it was introduced, no major new treatments have been developed. There are many reasons for a lack of progress, but perhaps the most fundamental is that to develop innovative treatments for depression, we must have a deeper understanding of the complex mood-generating systems within the brain and of what actually causes depression and its related mood and emotional disorders.

HDRF has developed a strategy of bringing together top neuroscience researchers, from various research institutions, with areas of expertise that complement each other, while providing the significant funds necessary for this group to collaboratively develop and execute the urgently needed, promising research programs. HDRF’s approach differs from and supplements the more conventional research pathway in which separate investigators at separate institutions work independently rather than share a common strategy.

HDRF’s current research roadmap begins with a focus on animal models to illuminate the neural circuits underlying depression and will end with the testing of new treatment approaches for depressed patients. To implement this effort, HDRF launched its Depression Task Force (DTF), a select group of world-renowned researchers, in 2010. This is an outstanding collaboration of leading neuroscience experts – each of them scientific pioneers in their own right – who have agreed to work as an integrated team to develop a unique program of depression research, based on the most advanced techniques in molecular biology, electrophysiology, and genetics. It is almost unprecedented for such successful investigators, each affiliated with a different university, to come together to work on a common project at a significant level of financial support (7-figure+.)

Studying animal models of depression has great potential because it makes it possible to directly examine tissue from the depressed brain, measure electrical activity at specific places in the brain, make genetic manipulations, study the short- and long-term impact of controlled stresses, and learn about the effect of hormones and drugs that might treat depression. One major challenge, however, has been finding the right animal models for human depression. This challenge can be addressed by applying clinical research on human depression to provide feedback to develop more useful animal models.

Such an iterative process of animal models guiding clinical research and clinical  research then refining the animal models will maximize our understanding of depression and position us to develop  specific new antidepressant medications and ultimately, to match the medication to the individual patient. The DTF is excellently positioned to advance such an approach.

In 2012, during a series of summits, the Depression Task Force (DTF) created a specific research plan to focus and guide their collaboration.  Each researcher is carrying out a piece of the plan in their own labs, and converging their ongoing results in our powerful Data Center, located at the University of Michigan.  Their strategy is to focus on “treatment-resistant” depression as the core of all depressive mind/brain illness, from chronic mild depression to Major Depressive Disorder.

The DTF have begun to identify imbalances in nerve circuits throughout key brain regions, as well as the microscopic connections between individual nerve cells in each region.  What is clear is that depression is not just a disruption in one brain area, but in many connected areas and circuits.  They are also studying the genes that regulate these circuits.  Their discoveries will provide answers for where and how we can intervene with potential new treatments for depressive mind/brain disorders.

Dr. Huda Akil, University of Michigan; Dr. Helen S. Mayberg, Mount Sinai School of Medicine; Dr. Elisabeth Binder, Institute of Psychiatry, Munich, Germany; Dr. René Hen, Columbia University; Dr. Eric Nestler, Mount Sinai School of Medicine; Dr. Michael Meaney, Douglas Institute & McGill University; Dr. Conor Liston, Feil Family Brain and Mind Research Institute; Dr. Jonathan Javitch, Columbia University; Dr. Kafui Dzirasa, Duke University