Resting brain perfusion in healthy carriers of the serotonin transporter promoter polymorphism

Abstract

The 5-HTTLP functional genetic polymorphism in the promoter region of the serotonin transporter gene (SERT) has been found to be associated with increased brain perfusion at rest in the amygdala and orbitofrontal cortex of healthy participants. The finding of changes in perfusion in brain regions known to be altered in depression suggests the existence of a measurable neurobiological correlate of the vulnerability to this disorder. In this study, we intended to replicate these findings in a much larger cohort of 183 healthy Caucasian individuals (97 females). Participants were aged between 18 and 45 years and underwent a standard T2-weighted structural brain scan and a baseline perfusion scan using continuous arterial spin-labeling. We did not detect any association between the SERT polymorphism and baseline brain perfusion in the regions of interest or elsewhere in the brain. In the amygdala, variability in baseline perfusion was explained in large part by global cerebral flow levels, in minor part by sex, but not by SERT genotype. This finding therefore fails to replicate existing reports on an effect of 5-HTTLPR genotype in the amygdala and in the orbitofrontal cortex in a larger cohort. For a sample of our size, power analyses suggested more than adequate detection capacity.