This application proposes Sanjaya Saxena, M.D. for a Mentored Patient-Oriented Research Career Development Award. The overall goals are to provide him with the conceptual background and research skills necessary for him to conduct patient-oriented research on obsessive-compulsive disorder (OCD) and major depressive disorder (MDD). Under the guidance of his Primary Mentor and Expert Consultants, he will be trained in neuroanatomy, neuropsychopharmacology, functional neuroimaging, quantitative image analysis, biostatistics, research design, and research ethics. Building upon his prior work in functional brain imaging in OCD and MDD, as well as in pharmacotherapy for refractory OCD, his research during the Award period will include two main studies, proposed herein, on the functional neuroanatomy, pharmacotherapy, and differential time course of response to treatment of OCD and MDD, studying a total of 42 subjects: 1) Cerebral Metabolic Changes with Treatment of Concurrent OCD and MDD: This study will use [18F]-fluoro-deoxyglucose positron emission tomography (FDG-PET), to delineate the specific brain system mediation of OCD symptoms and MDD symptoms occurring simultaneously, in patients treated with paroxetine, a medication shown to be effective for both disorders. Differential metabolic changes occurring along parallel, frontal-subcortical circuits within the same brain will be measured after four weeks and again, after twelve weeks of treatment, and will be correlated with changes in specific symptoms. Understanding the mediation of OCD and MDD by frontal-subcortical circuits, as well as the differential time course of pharmacological effects on these circuits, may lead to improved treatments for both of these common disorders in the future. 2) Cerebral Metabolic Predictors of Response to Paroxetine and Risperidone in Refractory OCD: This study has the following specific aims: a) to identify cerebral metabolic patterns with FDG-PET that might predict response to paroxetine alone vs. paroxetine plus risperidone, b) to identify symptoms or other clinical variables, such as level of insight or delusionality, which might predict response to adjunctive risperidone, and c) to examine the efficacy of adjunctive risperidone for OCD patients who are refractory to paroxetine. With the additional skills and experience acquired during the Award period, Dr. Saxena will be well-prepared to compete for independent research support, and to conduct patient-oriented, neuroimaging and pharmacological research on OCD and MDD, with the long-term goal of improving treatment for these disorders.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Mentored Patient-Oriented Research Career Development Award (K23)
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Treatment Assessment Review Committee (TA)
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Light, Enid
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University of California Los Angeles
Schools of Medicine
Los Angeles
United States
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Saxena, Sanjaya; Brody, Arthur L; Maidment, Karron M et al. (2007) Paroxetine treatment of compulsive hoarding. J Psychiatr Res 41:481-7
Brody, Arthur L; Mandelkern, Mark A; Lee, Grace et al. (2004) Attenuation of cue-induced cigarette craving and anterior cingulate cortex activation in bupropion-treated smokers: a preliminary study. Psychiatry Res 130:269-81
Saxena, Sanjaya; Brody, Arthur L; Maidment, Karron M et al. (2004) Cerebral glucose metabolism in obsessive-compulsive hoarding. Am J Psychiatry 161:1038-48
Saxena, Sanjaya; Brody, Arthur L; Ho, Matthew L et al. (2003) Differential brain metabolic predictors of response to paroxetine in obsessive-compulsive disorder versus major depression. Am J Psychiatry 160:522-32
Saxena, Sanjaya; Maidment, Karron M; Vapnik, Tanya et al. (2002) Obsessive-compulsive hoarding: symptom severity and response to multimodal treatment. J Clin Psychiatry 63:21-7
Saxena, Sanjaya; Brody, Arthur L; Ho, Matthew L et al. (2002) Differential cerebral metabolic changes with paroxetine treatment of obsessive-compulsive disorder vs major depression. Arch Gen Psychiatry 59:250-61
Saxena, S; Bota, R G; Brody, A L (2001) Brain-behavior relationships in obsessive-compulsive disorder. Semin Clin Neuropsychiatry 6:82-101
Saxena, S; Brody, A L; Ho, M L et al. (2001) Cerebral metabolism in major depression and obsessive-compulsive disorder occurring separately and concurrently. Biol Psychiatry 50:159-70
Brody, A L; Barsom, M W; Bota, R G et al. (2001) Prefrontal-subcortical and limbic circuit mediation of major depressive disorder. Semin Clin Neuropsychiatry 6:102-12