Serotonin modulation of cerebral glucose metabolism in normal aging

Age-related alterations in serotonin function may increase the vulnerability to psychiatric and neurodegenerative disorders in late life. The neuroendocrine and cerebral metabolic response to the acute administration of the selective serotonin reuptake inhibitor, citalopram (40 mg, IV), was measured in 17 normal control subjects using positron emission tomography (PET) to evaluate changes in serotonin function with normal aging. The citalopram-induced change in cerebral metabolism was positively correlated with age in the right precuneus, right paracentral lobule, and left middle temporal gyrus and negatively correlated with age in the left anterior cingulate gyrus, right inferior and middle frontal gyri, right insula, and right inferior parietal lobule. The positive correlations in mainly posterior brain regions indicate that normal aging is associated with an increase in metabolism after citalopram administration, whereas the negative correlations in mainly anterior brain regions indicate that normal aging is associated with a greater decrease in metabolism. These results suggest different compensatory processes in anterior compared to posterior brain regions secondary to the age-related loss of serotonin innervation.