Thursday, 21 August 2003
This presentation is part of : Approaches to Depression

S095-005 Serotonin Modulation of Cerebral Glucose Metabolism in Geriatric Depression

Gwenn S. Smith1, Elisse Kramer1, Carol Hermann1, Blaine Greenwald1, and Bruce Pollock2. (1) The Zucker Hillside Hospital, The North Shore-LIJ Health System, Glen Oaks, NY, USA, (2) University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

Objective: The ability to conduct in vivo studies of serotonergic function in neuropsychiatric disorders has been limited by the lack of safe and selective pharmacologic agents for the serotonin system and by the difficulties in the development of serotonin radiotracers. An approach has been developed to measure serotonin function by evaluating the cerebral metabolic effects of a single dose of the selective serotonin reuptake inhibitor (SSRI) citalopram administered intravenously (Smith et al., 2002). The goal of the present study was to evaluate the cerebral metabolic response to acute citalopram administration in patients with geriatric depression compared to age-matched controls.

Design: Two resting Positron Emission Tomography (PET) studies of cerebral glucose metabolism were performed after administration of a saline placebo infusion (Day 1) and after administration of citalopram (40mg, IV, Day 2). The patients were re-scanned after eight weeks of treatment with the oral medication.

Materials and Methods: Six patients with geriatric depression (one male/five females, mean age of 68.8, SD=5.7 years) who met DSM-IV criteria for current major depressive episode (non-bipolar, non-psychotic) and five comparison subjects (two males/three females, mean age of 64.8, SD= 4.3 years) were enrolled in the study. PET data acquisition was performed on the GE Advance PET tomograph 35 minutes after injection of [18F]-2deoxy-2-fluoro-D-glucose. The PET data were analyzed using the data driven voxel-wise analysis method, statistical parametric mapping (SPM99, Friston et al., 1995).

Results: The six depressed patients all met criteria for treatment response by week eight of treatment (defined as a Hamilton Depression Rating Scale Score below ten). The elderly control subjects demonstrated greater right cortical decreases relative to the patients, whereas the depressed patients demonstrated greater left cortical decreases relative to the controls. The depressed patients demonstrated greater increases relative to the controls in the right putamen and left occipital cortex. Chronic citalopram treatment resulted in progressive alterations in cerebral glucose metabolism in the patients.

Conclusion: These preliminary data provide evidence of a blunted right hemisphere cortical response and a less lateralized response to citalopram in the patients. Future studies in a larger sample of patients will evaluate whether the cerebral metabolic response to citalopram represents a biological marker of treatment outcome in geriatric depression. Supported in part by MH 64823, MH49936, MH57078, MH01621, MH 01509, MH 60575 and the General Clinical Research Center of the North Shore-LIJ Research Institute.

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