Neurobiological Mechanisms of Treatment Response in Geriatric Depression

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This is a resubmission of an application for a K-24 Midcareer Investigator Award in patient-oriented research (POR). The objectives of the award is to support career development of Helen Lavretsky, M.D. dedicated to understanding the underlying neurobiological mechanisms of treatment response in geriatric depression. The Career Development Plan will allow the candidate to: (1) develop an expertise in functional neuroimaging focused on the [F-18]fallypride positron emission tomography (PET) that is relevant to her ongoing investigation of the dopaminergic mechanisms of methylphenidate in geriatric depression; (2) extend her knowledge and skills to the use of functional MRI (fMRI) with the proposed coursework and tutorials; (3) enhance her ability to lead clinical studies with the use of biomarkers focused on treatment response in older patients with mood disorders complicated by cognitive impairment or caregiver stress; (4) improve her mentoring skills and her ability to recruit and mentor underrepresented minority and women trainees. The Mentoring Plan is targeted towards beginning investigators who want to learn to design and conduct patient-oriented research in late-life mood disorders. Under supervision by the candidate, trainees will obtain hands-on experience by conducting research in geriatric mood disorders, and by preparing scientific reports and entry-level K awards. The Research Plan is focused on the pilot use of the [F-18]fallypride PET to investigate the role of enhanced dopaminergic neurotransmission in the context of the clinical trial of methylphenidate (MPH) augmentation of citalopram to enhance clinical and cognitive outcomes in 16 subjects with geriatric depression. The primary aims of this study are to demonstrate that subjects receiving MPH with citalopram will experience greater decrease in the severity of depression and improvement in executive cognitive tests compared to those receiving citalopram+placebo, which will be related to the greater percent change in [(18)F] fallypride striatal/nonstriatal BP. With the support of this award, additional work proposed in this application will focus on the use and the mechanisms of mind-body interventions for geriatric depression.