Effects of sex, age, and aggressive traits in man on brain serotonin 5-HT_1A receptor binding potential measured by PET using [C-11]WAY-100635

Serotonin (5-HT) 1A receptors have been implicated in a variety of conditions including, depression, suicidal behavior, and aggression. Post-mortem brain studies and in vivo imaging studies report a variety of age and sex effects on brain 5-HT_1A binding. Behavioral data from 5-HT_1A specific pharmacological challenges suggest a role for 5-HT_1A receptors in aggression. The goal of the present study was to determine age, sex, and severity of life-time aggression effects on 5-HT_1A binding potential (BP) in vivo using positron emission tomography (PET) and the high affinity 5-HT_1A antagonist, [carbonyl-C-11]WAY-100635 in 12 healthy females (ages 41.0±15.7 years) and 13 healthy males (ages 39.6±15.5 years). Regions of interest included the dorsal raphe, anterior cingulate cortex, cingulate body, hippocampus, amygdala, medial prefrontal cortex (PFC), and orbital PFC. No significant correlation between age and BP was detected in any brain region. MANOVA of the first three principle components demonstrated a significantly higher BP in females compared with males (P=0.0127). Post-hoc tests confirmed sex differences (P<0.05) in the following regions: dorsal raphe, amygdala, anterior cingulate, cingulate body, medial PFC, and orbital PFC. The cerebellar volume of distribution was also significantly higher in females. There is a significant negative correlation between binding in several regions and lifetime aggression. We have replicated our post-mortem finding of higher 5-HT_1A binding in females compared to males. We did not detect an age dependent decrease in binding in males or females. Lower 5-HT_1A binding in more aggressive individuals is consistent with pharmacological challenge studies. Future studies should determine whether the binding is a state or trait effect.