Project Summary

Jon-Kar Zubieta, M.D., Ph.D. (Independent Investigator 2002) of University of Michigan, will use functional MRI to characterize the effect of early life stressors on the function of brain regions implicated in emotional regulation, and determine whether this effect is different between males and females by studying healthy males and females between the ages of 14 and 18 drawn from an ongoing longitudinal study of alcoholism risk. He will compare the response of emotional circuits in the brain to three different negative non-self-referring words, and response to negative emotional faces. Stressful events in childhood have been shown to increase the risk for the later development of depression, and severe or persistent stress has been shown to alter the brain both structurally and functionally similar to that observed in adults with episodes of Major Depression (MDE). Some of these changes appear to be associated with the long-term dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and elevated levels of cortisol. Severe stressors predict the onset of MDE, with a closer association for individuals at higher genetic risk. The association between stress and depression is observed across age groups and genders. Dr. Zubieta expects to see a dysregulation of emotional brain circuits in the high-stress group compared to the low-stress group, more apparent for challenges involving self-representation (self-referring negative affective words vs other negative stimuli). He also expects that this effect will be greater in females than males, and to be associated with elevations in stress hormone (cortisol) levels. Elucidation of stress-associated alterations in the neuronal circuitry involved in emotional regulation will allow further understanding on the pathways leading to risk for the development of MDE in males and females. This is turn can lead to novel and more individualized strategies for the prevention of Major Depression in childhood and teenage years.

Program Area: MOOD DISORDERS\Depression (Unipolar)

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