Predictors of Treatment Response in Late-Life Depression

University Of Pittsburgh At Pittsburgh, Pittsburgh PA

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Abstract

This proposal is for a K23 Mentored Patient-Oriented Research Career Development Award. The applicant is a geriatric psychiatrist at the University of Pittsburgh who proposes to develop the skills necessary to bridge intervention research in geriatric psychiatry with cognitive neuroscience. Career development activities will focus on functional MRI methods and data analysis, with an emphasis on the challenges of conducting and interpreting functional imaging studies in the psychiatrically ill elderly. These skills will be applied to intervention research in late-life depression (LLD), which will be conducted under the auspices of the Mental Health Intervention Research Center for Late-Life Mood Disorders (MHIRC/LLMD). The applicant will develop expertise and a program of research to investigate the functional neuroanatomy of late-life depression using functional MRI and computational modeling. Initial efforts will focus on identifying in individuals with LLD functional interactions among brain areas associated with depression i.e., the anterior cingulate cortex (ACC), dorsolateral prefrontal cortex (DLPFC), caudate nucleus, and hippocampus. This methodology will permit the testing of hypotheses about the functioning of specific brain regions in LLD versus healthy elderly populations, and further understanding of cognitive changes known to be associated with LLD. During the second phase of the career development plan, the fMRI results obtained in the first phase will be used to refine a computational model of how changes to these specific brain regions (such as through Alzheimer's disease and cerebrovascular disease) interact with LLD. The model will be used to generate hypotheses about how pre-treatment fMRI scans predict the course of LLD treatment response. The hypotheses will be tested using longitudinal follow-up data (i.e., post-treatment), obtained in association with an ongoing MHIRC/LLMD protocol. Repeat fMRI will also be performed post-treatment to investigate the neural basis of treatment response. This award will support the applicant in obtaining the training necessary to undertake this direction of research and to develop as an independent scientist.