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Serotonin transporter occupancy and the functional neuroanatomic effects of citalopram in geriatric depression

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Sacher,  Julia
Centre for Addiction and Mental Health, University of Toronto, ON, Canada;
Department of Psychiatry, University Health Network, University of Toronto, ON, Canada;
Clinic for Cognitive Neurology, University of Leipzig, Germany;
Department Neurology, MPI for Human Cognitive and Brain Sciences, Max Planck Society;

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Citation

Smith, G. S., Kahn, A., Sacher, J., Rusjan, P., van Eimeren, T., Flint, A., et al. (2011). Serotonin transporter occupancy and the functional neuroanatomic effects of citalopram in geriatric depression. The American Journal of Geriatric Psychiatry, 19(12), 1016-1025. doi:10.1097/JGP.0b013e318227f83f.


Cite as: http://hdl.handle.net/11858/00-001M-0000-0012-1198-8
Abstract
Objectives 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. Design 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. Setting Psychiatric outpatient clinic. Participants Seven depressed patients who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for current major depressive episode were enrolled. Intervention Patients underwent a 12-week open-label trial of the SSRI, citalopram. Measurements 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). Results 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. Conclusion 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.