Regional differences in SERT occupancy after acute and prolonged SSRI intake investigated by brain PET

Blocking of the serotonin transporter (SERT) represents the initial mechanism of action of selective serotonin reuptake inhibitors (SSRIs) which can be visualized due to the technical proceedings of SERT occupancy studies. When compared to the striatum, higher SERT occupancy in the midbrain and lower values in the thalamus were reported. This indicates that occupancy might be differently distributed throughout the brain, which is supported by preclinical findings indicating a regionally varying SERT activity and antidepressant drug concentration. The present study therefore aimed to investigate regional SERT occupancies with positron emission tomography and the radioligand [11C]DASB in 19 depressed patients after acute and prolonged intake of oral doses of either 10 mg/day escitalopram or 20 mg/day citalopram. Compared to the mean occupancy across cortical and subcortical regions, we detected increased SERT occupancies in regions commonly associated with antidepressant response, such as the subgenual cingulate, amygdala and raphe nuclei. When acute and prolonged drug intake was compared, SERT occupancies increased in subcortical areas that are known to be rich in SERT. Moreover, SERT occupancy in subcortical brain areas after prolonged intake of antidepressants was predicted by plasma drug levels. Similarly, baseline SERT binding potential seems to impact SERT occupancy, as regions rich in SERT showed greater binding reduction as well as higher residual binding. These findings suggest a region-specific distribution of SERT blockage by SSRIs and relate the postulated link between treatment response and SERT occupancy to certain brain regions such as the subgenual cingulate cortex.