This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. OBJECTIVE: We propose to utilize a newly developed system for combined transcranial magnetic stimulation (TMS) and positron emission tomography (PET) to study connectivity between the prefrontal cortex (PFC) and limbic and paralimbic regions in patients suffering from unipolar depression (major depressive disorder). We hypothesize that there are abnormalities in connectivity between the left dorsolateral PFC, limbic, and striatal regions in unipolar depression, which could be a key element in the pathophysiology of this illness. These areas are part of brain neuroanatomic circuits involved in mood regulation which are thought to be abnormal in unipolar depression. Even though there is evidence suggesting anatomical and functional abnormalities in brain regions participating in these neuroanatomic circuits in unipolar depressed patients, the hypothesis of abnormalities in connectivity among these brain regions has not been examined. RESEARCH PLAN: We propose to take advantage of a new development in imaging methodology that has recently become available in our Research Imaging Center with a PET/TMS device that utilizes a robotic arm for more precise targeting of the TMS stimuli coupled with measurement of response in brain activation with O-15 (H2O) PET. METHODS: Patients will have the left dorsolateral PFC stimulated with TMS, and responsiveness as reflected by changes in neuronal activation in remote limbic and striatal regions will be measured with O-15 (H2O) PET. The patients (n=20) will be studied in the untreated state and compared to a group of healthy controls (n=20). CLINICAL
We will utilize this newly developed in vivo imaging tool to study brain connectivity in depressed subjects, and to further examine the pathophysiology of unipolar depression. This protocol can contribute to the elucidation of the brain mechanisms involved in causation of depression. Ultimately, it could contribute to the development of novel approaches to the treatment of this severe mental illness.
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