Project Summary

Jon-Kar Zubieta, M.D., Ph.D. (Independent Investigator 2004) of University of Michigan, plans on studying how problems in responding to stress may be playing a role in major depression disorder. Stressful events have been shown to increase the risk for the development of major depression. And dysregulation of stress responses is seen in some major depression patients, however these have been examined primarily using neuroendocrine markers. Dysregulation has been associated with a more protracted illness course and poorer responses to SSRI antidepressants. In the proposed research, Dr. Zubieta plans to measure the functional responses of a stress-activated neurotransmitter system, the endogenous opioid and mu opioid receptors, centrally involved in adaptations to stress, in patients diagnosed with major depressive disorder and in matched healthy controls using PET scanning. Subjects will be exposed to minor muscular pain as a stressor and patients will be monitored before and after antidepressant treatment. The experiments will provide information about the regional patterns and magnitude of activation of stress-response circuits in major depression. The study will also study the relationship of major depression to pain responses, and the effect of antidepressants on these measures. The latter question is important due to the frequent comorbidity of persistent pain syndromes and major depression disorder.

Program Area: MOOD DISORDERS\Unipolar Depression

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