This K07 Clinical Mental Health Academic Award application in Geriatric Psychiatry has been revised based upon recommendations of the Review Committee. It will provide five years of support for special study and supervised research to prepare the applicant for a career investigating the effects of depression on aging and a faculty leadership role as Director of Research, Division of Geriatric Psychiatry. The Development Plan for nominee outlines goals and activities which will support these endeavors. The primary goal of the Award is to develop expertise in neuroimaging and apply that expertise to the study of the relationship between MRI measures of brain neuromorphometry and age-related changes in patients with early onset major depression. Secondary goals include learning about neuropsychological changes, changes in HPA axis sensitivity, and the conceptualization and measurement of course of illness variables associated with aging. The proposed research project """"""""Age-related hippocampal volume loss in MDD"""""""" seeks to define the nature of changes in brain structures due to recurrent episodes of depression. It is hypothesized that recurrent depression may accelerate normal hippocampal aging, perhaps through neuronal glucocorticoid toxicity resulting from depression-induced hypercortisolemia. In pilot work, the applicant found hippocampal volumes to be decreased in elderly depressed patients, and a correlation between volume reduction and duration of depression. A cross-sectional study of 40 medically healthy patients, ages 30-80, with recurrent early onset major depression and 40 pair-wise matched controls will test for differences in regional brain structure volumes, cognitive function, HPA axis function, and clinical variables. Hypotheses to be tested are that, relative to controls, patients with depression will show: 1) greater age-related decreases in hippocampal and frontal lobe volumes and increases in temporal horn volumes, with no between group differences for occipital lobe and intracerebral volumes, or volume of white matter abnormalities; 2) greater age-related deficits in performance on Benton;'s Visual Retention Test, paragraph recall, verbal fluency and Stroop Color-Word Interference Test; and 3) grater increases in plasma cortisol levels following administration of dexamethasone. 4) Hippocampal and frontal lobe volume reduction will be directly correlated with cumulative burden of depression.
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