This Mentored Clinical Scientist Development Award (MCSDA) application defines a training program to facilitate the development of the Pl as an independent researcher in the area of mood disorders. The educational activities outlined will enable the Pl to explore the biological basis of corticosteroid effects on brain function. During the course of this award, Dr. A. John Rush will serve as the PI's mentor. Additional experts providing instruction and training include: Drs. Frederick Petty (clinical trials), Bruce S. McEwen (glucocorticoids and the hippocampus), and Alan Frol and C. Munro Cullum (cognitive neuroscience). Measurement of hippocampal volumes from MRI scans will be performed by Dr. John Csernansky's group at Washington University. The training entails increasing the PI's knowledge of neuropsychological testing and clinical research methodology. The Pl plans to use cognitive testing to develop a paradigm in humans for exploring pharmacologic interventions which may prevent or reverse hippocampal changes associated with corticosteroids. In order to achieve the stated training goals, the Pl has developed a program that includes didactic courses, tutorials, and a research project. The proposed project will afford a hands-on experience, reinforcing the information and techniques learned through mentoring and classroom environments. The Pl will first examine memory, mood, and hippocampal volume in asthma and rheumatoid arthritis patients receiving chronic oral prescription corticosteroid therapy, a population the Pl has actively researched for over three years. In animals, agents which inhibit the release of glutamate appear to prevent and reverse hippocampal damage secondary to corticosteroids. Thus, the first experiment in the training plan will be followed by a clinical trial of the glutamate release inhibitor, lamotrigine, to determine if neurocognitive changes associated with corticosteroids can be reversed in humans. Through this award, the Pl will extend his previous research experience by adding new skills and knowledge which will be used for investigations at the interface of neuroscience and clinical research.
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