Archival Report| Volume 66, ISSUE 3, P259-266, August 01, 2009

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Serotonin Modulation of Cerebral Glucose Metabolism in Depressed Older Adults

  • Gwenn S. Smith
    Address reprint requests to Gwenn S. Smith, Ph.D., Division of Geriatric Psychiatry and Neuropsychiatry, Johns Hopkins University School of Medicine, Johns Hopkins Bayview Medical Center, 5300 Alpha Commons Drive, Fourth Floor, Baltimore, MD 21224
    Department of Psychiatry Research, the Zucker Hillside Hospital, Glen Oaks, New York

    Center for Neurosciences, The Feinstein Institute for Medical Research, North Shore - Long Island Jewish Health System, Manhasset, New York
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  • Elisse Kramer
    Department of Geriatric Psychiatry, the Zucker Hillside Hospital, Glen Oaks, New York
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  • Carol Hermann
    Department of Geriatric Psychiatry, the Zucker Hillside Hospital, Glen Oaks, New York
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  • Yilong Ma
    Center for Neurosciences, The Feinstein Institute for Medical Research, North Shore - Long Island Jewish Health System, Manhasset, New York
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  • Vijay Dhawan
    Center for Neurosciences, The Feinstein Institute for Medical Research, North Shore - Long Island Jewish Health System, Manhasset, New York
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  • Thomas Chaly
    Center for Neurosciences, The Feinstein Institute for Medical Research, North Shore - Long Island Jewish Health System, Manhasset, New York
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  • David Eidelberg
    Center for Neurosciences, The Feinstein Institute for Medical Research, North Shore - Long Island Jewish Health System, Manhasset, New York
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      Monoamine dysfunction, particularly of the serotonin system, has been the dominant hypothesis guiding research and treatment development in affective disorders. The majority of research has been performed in midlife depressed adults. The importance of understanding the neurobiology of depression in older adults is underscored by increased rates of mortality and completed suicide and an increased risk of Alzheimer's dementia. To evaluate the dynamic response of the serotonin system, the acute effects of citalopram infusion on cerebral glucose metabolism was measured in depressed older adults and control subjects. The hypothesis was tested that smaller decreases in metabolism would be observed in cortical and limbic regions in depressed older adults relative to control subjects.


      Sixteen depressed older adults and 13 control subjects underwent two resting positron emission tomography (PET) studies with the radiotracer [18F]-2-deoxy-2-fluoro-D-glucose after placebo and citalopram infusions.


      In control subjects compared with depressed older adults, greater citalopram-induced decreases in cerebral metabolism were observed in the right anterior cingulate, middle temporal (bilaterally), left precuneus, and left parahippocampal gyri. Greater decreases in the depressed older adults than control subjects were observed in left superior and left middle frontal gyri and increases in left inferior parietal lobule, left cuneus, left thalamus, and right putamen.


      In depressed older adults relative to control subjects, the cerebral metabolic response to citalopram is blunted in cortico-cortical and cortico-limbic pathways and increased in the left hemisphere (greater decrease interiorly and increases posteriorly). These findings suggest both blunted and compensatory cerebral metabolic responses to citalopram in depressed older adults.

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