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. Among the aged, major depression is a common problem which causes significant morbidity and mortality. While effective treatments exist for major depression in the elderly, the speed, extent, and permanence of treatment response are unpredictable and vary widely, thus leaving considerable residual symptoms and disability. As functional neuroimaging with positron emission tomography (PET) allows for the direct examination of the structure and functioning of the brain, this represents a promising approach to investigate the underlying mechanisms of treatment response variability. In studies with mid-life affective disorder patients, functional neuroimaging is beginning to help clarify the neuroanatomical correlates and circuitry of major depression and treatment response (Drevets 1998, Kennedy et al. 1997, and Mayberg et al. 1997). Among elderly patients, however, the increased risk of medical, cerebrovascular and dementing illnesses, and the pharmacokinetic differences associated with aging challenge the generalizability of these early and mid-life studies to late-life. The relationship between regional cerebral glucose metabolism as measured by 18F-fluorodeoxyglucose (FDG) PET and treatment response variability with paroxetine in elderly depressed patients is being examined. It is hypothesized that in elderly patients (age 60-80) with major depression, pre-treatment anterior cingulate hypermetabolism on glucose PET scans will positively correlate with extent, speed, and permanence of treatment response to the antidepressant paroxetine. An expansion of the K23 project is proposed by examining paroxetine exposure and its relation to clinical response and side effects and to perform repeat FDG PET scans on age-matched normal controls at the same time intervals as the depressed patients in the K23 project (baseline and 11 weeks).
Specific aims are: (1) Determine the role of medication compliance and paroxetine exposure in contributing to treatment response variability. (2) Examine the frequency of hyponatremia in relation to antidepressant therapy and medical comorbidity in these elderly depressed patients. (3) Determine in elderly normal controls whether there are retest effects of the FDG PET procedure on regional cerebral metabolism after 11 we
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