Abstract
484
Objectives The brain serotonin (5-HT) system is involved in the regulation of appetite. In animal models, a hyposerotonergic state leads to increased food intake and weight gain. We have previously found a positive correlation between BMI and neocortical 5-HT2A receptor binding and a negative correlation to cerebral 5-HT transporter binding. These observations have been interpreted as compensatory regulations in response to low level of synaptic serotonin in obese subjects. We have recently found an upregulation of the 5-HT4 receptor in an animal model of serotonin depletion and that a paroxetine-induced increase in the serotonin level, is associated with a decrease in the 5-HT4 receptor density. Since the 5-HT4 receptor thus seems to be sensitive to changes in cerebral serotonin levels, we hypothesized that there would be a positive association between BMI and cerebral 5-HT4 receptor binding.
Methods 28 healthy subjects (age range 20.5-78.2 y, median 38.5 y) with BMI ranging from 20.5-40.5 kg/m2 (median 24.2 kg/m2) were included. The BPND of the 5-HT4 receptor was determined using 120 min dynamic [11C]-SB207145 PET and the SRTM with cerebellum as the reference region. Data was analyzed using linear regression with age as covariate; averaged bilateral brain regions included a high-binding region (striatum), a medium-binding region (hippocampus), and a low-binding region (neocortex).
Results The 5-HT4 binding was significantly positively correlated to BMI in all investigated brain regions: Neocortex (p=0.01, r=0.54), hippocampus (p=0.03, r=0.38), and striatum (p=0.04, r=0.41).
Conclusions This finding supports the previous studies of serotonergic markers and obesity: In overweight subjects endogenous brain serotonin levels seem to be low.
- © 2009 by Society of Nuclear Medicine