Reduced serotonin receptors and transporters in normal aging adults: a meta-analysis of PET and SPECT imaging studies

Abstract

Age-related alterations in serotonin (5-HT) function have been hypothesized to underlie a range of physiological, emotional, and cognitive changes in older age. Here, we conducted a quantitative synthesis and comparison of the effects of age on 5-HT receptors and transporters from cross-sectional PET and SPECT imaging studies. Random-effects meta-analyses of 31 studies including 1087 healthy adults yielded large negative age effects in 5-HT-2A receptors, moderate negative age effects in 5-HT transporters, and small negative age effects in 5-HT-1A receptors. Age differences were significantly larger in 5-HT-2A receptors compared to 5-HT-1A receptors. A meta-regression showed that 5-HT target, brain region, tracer kinetic measure, radionuclide, and publication year significantly moderated the age effect. The findings overall identify reduced serotonergic signal transmission in age. The evidence for a relative preservation of 5-HT-1A compared to 5-HT-2A receptors may partially explain differential psychological changes with age, such as why older people use more emotion-focused rather than problem-focused coping strategies.