Serotonin modulation of cerebral glucose metabolism in depressed older adults.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Smith
Gwenn S
GS
Department of Psychiatry Research, the Zucker Hillside Hospital, Glen Oaks, New York, USA. gsmith95@jhmi.edu
Kramer
Elisse
E
Hermann
Carol
C
Ma
Yilong
Y
Dhawan
Vijay
V
Chaly
Thomas
T
Eidelberg
David
D
D000368:Aged; D001931:Brain Mapping; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology*; D015283:Citalopram / Q000627:therapeutic use; D003863:Depression / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D019788:Fluorodeoxyglucose F18; D015577:Geriatric Assessment; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D008297:Male; D008609:Mental Status Schedule; D008875:Middle Aged; D049268:Positron-Emission Tomography / Q000379:methods; D012701:Serotonin / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use
D015283:Citalopram; D019788:Fluorodeoxyglucose F18; D005947:Glucose; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors