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

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 positron emission tomography and single-photon emission computed tomography imaging studies. Random-effects meta-analyses of 31 studies including 1087 healthy adults yielded large negative effects of age in 5-HT-2A receptors (largest in global cortex), moderate negative effects of age in 5-HT transporters (largest in thalamus), and small negative effects of age in 5-HT-1A receptors (largest in parietal cortex). Presynaptic 5-HT-1A autoreceptors in raphe/midbrain, however, were preserved across adulthood. Adult age differences were significantly larger in 5-HT-2A receptors compared with 5-HT-1A receptors. A meta-regression showed that 5-HT target, radionuclide, and publication year significantly moderated the age effects. The findings overall identify reduced serotonergic signal transmission in healthy aging. The evidence for the relative preservation of 5-HT-1A compared with 5-HT-2A receptors may partially explain psychological age differences, such as why older adults use more emotion-focused rather than problem-focused coping strategies.