Serotonin Transporter Occupancy and the Functional Neuroanatomic Effects of Citalopram in Geriatric Depression

Abstract

The functional neuroanatomic changes associated with selective serotonin reuptake inhibitor (SSRI) treatment have been the focus of positron emission tomography (PET) studies of cerebral glucose metabolism in geriatric depression. To evaluate the underlying neurochemical mechanisms, both cerebral glucose metabolism and serotonin transporter (SERT) availability were measured before and during treatment with the SSRI, citalopram. It was hypothesized that SERT occupancy would be observed in cortical and limbic brain regions that have shown metabolic effects, as well as striatal and thalamic regions that have been implicated in prior studies in midlife patients. Psychiatric outpatient clinic. Seven depressed patients who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for current major depressive episode were enrolled. Patients underwent a 12-week open-label trial of the SSRI, citalopram. Patients underwent high-resolution research tomography PET scans to measure changes in cerebral glucose metabolism and SERT occupancy by citalopram treatment (after 8-10 weeks of treatment). Three different tracer kinetic models were applied to the [¹¹C]-DASB region-of-interest data and yielded similar results of an average of greater than 70% SERT occupancy in the striatum and thalamus during citalopram treatment. Voxel-wise analyses showed significant SERT occupancy in these regions, as well as cortical (e.g., anterior cingulate, superior and middle frontal, precuneus, and limbic (parahippocampal gyrus) areas that also showed reductions in glucose metabolism. The findings suggest that cortical and limbic SERT occupancy may be an underlying mechanism for the regional cerebral metabolic effects of citalopram in geriatric depression.