Cognition and Treatment Outcomes of Geriatric Depression

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DESCRIPTION (provided by applicant): This is a resubmission of a proposal for a K23 Patient-Oriented Mentored Scientist Award. The applicant is a clinical psychologist, who proposes to develop the skills necessary for independent investigator's career focusing on the use of cognitive and affective neuroscience methods in studies of geriatric depression and its treatment. Recent clinical and neuroimaging findings suggest that abnormalities in ventral limbic and dorsal cortical regulation contribute to late-life depression and some of these abnormalities even influence the response of depression to treatment. Traditional neuropsychological tests, while useful for diagnosis and clinical care, often assess complex cognitive and affective functions without sufficient specificity to contribute to studies of specific neural networks. In contrast, tests originating from cognitive neuroscience paradigms have begun to be used in studies of specific neural networks in humans. The scientific and clinical potential of this approach in clinical settings has been recognized by the NIMH Workgroup, "Neurocognitive Outcome Measures in 21st Century Clinical Trials: Advancing the Translation of Cognitive Neuroscience" that urged the field to develop and implement assessment tools that are informed by cognitive assays in order to: 1) advance the understanding of neurocognitive function in clinical disorders; and 2) allow for refined theoretical and clinical research. The training and research proposed in this application aims to prepare the applicant to respond to the above mandate. Formal coursework, tutorials, collaborative studies, and paper writing all were planned with the goal of giving the applicant substantive knowledge in cognitive and affective neuroscience of depression and of aging, experimental skills in task development and test validation techniques, as well as training in clinical trials methodology. Mentors and experts from Cornell, Washington University, and the University of Wisconsin were selected with complementary expertise in areas relevant to the applicant's training needs. The process and content of the training experience was designed in a way that it can give the applicant the opportunity to best benefit from interaction with his mentors. Moreover, the applicant will pursue a research project that can function as the training ground for accomplishing his educational objectives. The project will investigate the function of three attentional networks (conflict, alerting, vigilance) in late-life depression and hypothesizes that: 1) All three are impaired in late-life depression; 2) All three remain impaired even after improvement of depression; but 3) Only impairment in the conflict network is associated with poor treatment response to an antidepressant (citalopram).