Geriatric depression is a significant public health problem as it is associated with disability in the performance of activities of daily living, with a dramatic increase in the rate of completed suicide and with greater mortality in the medically ill elderly. The clinical response to antidepressant treatment in geriatric depressed patients is delayed and the course of antidepressant response is highly variable. Even though there are effective antidepressant agents available, some patients are still refractory to treatment. An understanding of the neurobiology of geriatric depression, particularly of the serotonin function, may have implications for the clinical management of this disorder. The ability to study serotonergic function in vivo has been limited by the lack of safe and selective pharmacologic agents and limitations of the available serotonin radiotracers. The principal investigator and her colleagues have developed a direct and non-invasive method of measuring serotonergic function in vivo. These considerations provided the impetus for the proposed study to evaluate the pathophysiology of the serotonin system in normal aging and in geriatric depression using Positron Emission Tomography (PET) methods to measure the cerebral metabolic response to the acute, intravenous administration of a selective serotonin reuptake inhibitor (citalopram, celexa), as well as to chronic treatment with the oral medication. PET studies of cerebral glucose metabolism are sensitive to detecting functional anatomic changes and are sensitive to the effects of antidepressant treatment in depressed patients. The significance of the proposed studies is underscored by the lack of functional neuroanatomic data and the lack of in vivo neurobiologic studies of serotonin function in geriatric depression. The proposed studies will provide fundamental data regarding the functional neuroanatomy of geriatric depression and the functional responsiveness of the serotonin system, based on the evaluation of acute and chronic serotonin reuptake inhibition. As glucose metabolic activity represents the final common pathway of neurochemical activity in the brain, these findings would direct subsequent studies to characterize the neurochemical pathways underlying the regional changes using PET and neuroreceptor radiotracers.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
7R01MH064823-05
Application #
7289649
Study Section
Special Emphasis Panel (ZRG1-BDCN-6 (01))
Program Officer
Evans, Jovier D
Project Start
2003-04-01
Project End
2008-08-31
Budget Start
2006-12-15
Budget End
2008-08-31
Support Year
5
Fiscal Year
2006
Total Cost
$88,068
Indirect Cost
Name
Centre for Addiction and Mental Health
Department
Type
DUNS #
207855271
City
Toronto
State
ON
Country
Canada
Zip Code
M5S2S-1
Marano, Christopher M; Workman, Clifford I; Lyman, Christopher H et al. (2015) Structural imaging in late-life depression: association with mood and cognitive responses to antidepressant treatment. Am J Geriatr Psychiatry 23:4-12
Hirao, Kentaro; Smith, Gwenn S (2014) Positron emission tomography molecular imaging in late-life depression. J Geriatr Psychiatry Neurol 27:13-23
Marano, Christopher M; Workman, Clifford I; Lyman, Christopher H et al. (2014) The relationship between fasting serum glucose and cerebral glucose metabolism in late-life depression and normal aging. Psychiatry Res 222:84-90
Marano, Christopher M; Workman, Clifford I; Kramer, Elisse et al. (2013) Longitudinal studies of cerebral glucose metabolism in late-life depression and normal aging. Int J Geriatr Psychiatry 28:417-23
Munro, Cynthia A; Workman, Clifford I; Kramer, Elisse et al. (2012) Serotonin modulation of cerebral glucose metabolism: sex and age effects. Synapse 66:955-64
Diaconescu, Andreea Oliviana; Kramer, Elisse; Hermann, Carol et al. (2011) Distinct functional networks associated with improvement of affective symptoms and cognitive function during citalopram treatment in geriatric depression. Hum Brain Mapp 32:1677-91
Gunning, Faith M; Smith, Gwenn S (2011) Functional neuroimaging in geriatric depression. Psychiatr Clin North Am 34:403-22, viii
Smith, Gwenn S; Workman, Clifford I; Kramer, Elisse et al. (2011) The relationship between the acute cerebral metabolic response to citalopram and chronic citalopram treatment outcome. Am J Geriatr Psychiatry 19:53-63
Smith, Gwenn S; Kahn, Alan; Sacher, Julia et al. (2011) Serotonin transporter occupancy and the functional neuroanatomic effects of citalopram in geriatric depression. Am J Geriatr Psychiatry 19:1016-25
Smith, Gwenn S; Kramer, Elisse; Ma, Yilong et al. (2009) Cholinergic modulation of the cerebral metabolic response to citalopram in Alzheimer's disease. Brain 132:392-401

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