Jon-Kar Zubieta, M.D., Ph.D.
“Imaging technologies have allowed us to look at brain circuitry, the mechanisms that are actually involved in depression, bipolar disorder, and other related illnesses, to try to understand how that information has meaning at the individual level.”
Jon-Kar Zubieta, M.D., Ph.D., is driven to understand the underpinnings of depression at the molecular level. Using imaging technology as his guide, he explores the deeply mystifying territory of the human brain in the quest for greater understanding of mood disorders at their most basic level.
By allowing researchers to examine the physical mechanisms of brain circuitry involved in depression, bipolar disorder, and related illnesses, imaging technologies have permitted research in mood disorders and stress response to forge ahead rapidly in the last 10 years, Zubieta says. Zubieta sees nearly boundless possibilities for the discoveries that the future application of these tools may produce.
“What we are doing right now is taking that information and trying to understand how it pertains to the particular individual. The treatment response - can you predict it? Can we select different treatments based on a particular biomarker? This could be genetic factors, this could be endocrine factors, which could be immunological factors, brain imaging, and so forth. And the most exciting research right now in the field I think is one that tries to incorporate all these perspectives into a systems view of these illnesses,” he says.
Zubieta’s research focuses on the neurochemical, brain, and functional changes involved in depression, substance abuse disorders, and stress response regulation. He and his research team are also investigating the role of physical and emotional stressors in a variety of conditions, including pain. Zubieta, who is the Phil F. Jenkins Research Professor of Depression in the Department of Psychiatry, has been widely recognized for his major study of the “placebo effect,” the phenomenon that makes some people feel better after receiving a simulated treatment that they believe is real.
In the study, the people who expected their pain to improve after receiving a (placebo) painkiller were those who reported the greatest benefit post-treatment. This led to the finding that an individual’s response to placebo treatment is strongly associated with the level of activity in an area of the brain that anticipates reward, suggesting that the placebo effect may be a mechanism of resiliency. This work also suggests that studies of new therapies may benefit from considering individual ability to anticipate reward. And, since many people respond as well to placebo as to active treatment, there may be many untapped opportunities to harness the placebo effect for the benefit of patients.
Moving toward a future in which personalized medicine as a reality, for Zubieta, requires the recognition that just as every individual’s brain is truly unique from all others, so too do brain illnesses affect each person distinctly. “Understanding that variability, and how that variability impacts on the individual propensity to develop the disease, and once you develop a disease, the professional treatment outcomes or different treatments that can be used – that’s where we are going,” he says.
What excites him is the recognition of depression and bipolar disorder as true biological illnesses, that psychiatry, psychology, neurology, and, a bit more gradually, primary care, have arrived at the understanding that depression involves alterations in brain structure and chemistry, “that this is not just the imagination of the individual, that this is a real illness and we are pathologically attached to it,” he says.
In Zubieta’s view, the Depression Center has done a great deal to establish depression as a true medical illness, as well as facilitate connections between disciplines that may not have frequent or natural opportunities for partnership. Zubieta calls the Depression Center “an avenue for collaboration for us to interface with our colleagues across many different fields under one umbrella,” with investigators “who may be looking at these problems in slightly different ways,” he says. “By being able to collaborate more, we also create more informative science, and we learn more about what is going on with these illnesses.”