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Serotonin modulation of cerebral glucose metabolism in depressed older adults.

ABSTRACT: 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.

SUBMITTER: Smith GS

PROVIDER: S-EPMC2706292 | biostudies-literature | 2009 Aug

REPOSITORIES: biostudies-literature

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Serotonin modulation of cerebral glucose metabolism in depressed older adults.

Smith Gwenn S GS Kramer Elisse E Hermann Carol C Ma Yilong Y Dhawan Vijay V Chaly Thomas T Eidelberg David D

Biological psychiatry 20090415 3

<h4>Background</h4>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 sy ...[more]

PMID: 19368900

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Project description:ObjectiveWe examined the associations of symptoms of sleep-disordered breathing (SDB), which was defined as loud snoring, stopping breathing for a while during sleep, and daytime sleepiness, and insomnia with glucose metabolism and incident type 2 diabetes in older adults.Research design and methodsBetween 1989 and 1993, the Cardiovascular Health Study recruited 5,888 participants ≥65 years of age from four U.S. communities. Participants reported SDB and insomnia symptoms yearly through 1989-1994. In 1989-1990, participants underwent an oral glucose tolerance test, from which insulin secretion and insulin sensitivity were estimated. Fasting glucose levels were measured in 1989-1990 and again in 1992-1993, 1994-1995, 1996-1997, and 1998-1999, and medication use was ascertained yearly. We determined the cross-sectional associations of sleep symptoms with fasting glucose levels, 2-h glucose levels, insulin sensitivity, and insulin secretion using generalized estimated equations and linear regression models. We determined the associations of updated and averaged sleep symptoms with incident diabetes in Cox proportional hazards models. We adjusted for sociodemographics, lifestyle factors, and medical history.ResultsObserved apnea, snoring, and daytime sleepiness were associated with higher fasting glucose levels, higher 2-h glucose levels, lower insulin sensitivity, and higher insulin secretion. The risk of the development of type 2 diabetes was positively associated with observed apnea (hazard ratio [HR] 1.84 [95% CI 1.19-2.86]), snoring (HR 1.27 [95% CI 0.95-1.71]), and daytime sleepiness (HR 1.54 [95% CI 1.13-2.12]). In contrast, we did not find consistent associations between insomnia symptoms and glucose metabolism or incident type 2 diabetes.ConclusionsEasily collected symptoms of SDB are strongly associated with insulin resistance and the incidence of type 2 diabetes in older adults. Monitoring glucose metabolism in such patients may prove useful in identifying candidates for lifestyle or pharmacological therapy. Further studies are needed to determine whether insomnia symptoms affect the risk of diabetes in younger adults.

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Serotonin modulation of cerebral glucose metabolism in depressed older adults.

Publications

Serotonin modulation of cerebral glucose metabolism in depressed older adults.

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