Age and sex dependent variability of type 2 dopamine receptors in the human brain: A large-scale PET cohort

BACKGROUND The dopamine system contributes to a multitude of functions ranging from reward and motivation to learning and movement control, making it a key component in goal-directed behavior. Altered dopaminergic function is observed in neurological and psychiatric conditions. Numerous factors have been proposed to influence dopamine function, but due to small sample sizes and heterogeneous data analysis methods in previous studies their specific and joint contributions remain unresolved. METHODS In this cross-sectional register-based study we investigated how age, sex, body mass index (BMI), as well as cerebral hemisphere and regional volume influence striatal type 2 dopamine receptor (D 2 R) availability in the human brain. We analyzed a large historical dataset (n=156, 120 males and 36 females) of [11C]raclopride PET scans performed between 2004 and 2018. RESULTS Striatal D 2 R availability decreased through age for both sexes and was higher in females versus males throughout age. BMI and striatal D 2 R availability were weakly associated. There was no consistent lateralization of striatal D 2 R. The observed effects were independent of regional volumes. These results were validated using two different spatial normalization methods, and the age and sex effects also replicated in an independent sample (n=135). CONCLUSIONS D 2 R density is dependent on age and sex, which may contribute to the vulnerability of neurological and psychiatric conditions involving altering D 2 R expression.