Maximal serotonin transporter (5-HTT) densities have been found in the cingulate cortex, a cortical region that has been critically implicated in emotion processing and the pathophysiology of Major Depressive Disorder. Furthermore, serotonin (5-HT) re-uptake inhibition is the first line strategy in the treatment of depression.

Since 5-HTTs are not restricted to neuronal cells, 5-HT uptake velocity (Vmax) can be easily measured on blood platelets subserving as peripheral model of neuronal 5-HTT function and related measures of neural activation.

To determine whether peripheral 5-HTT uptake velocity is related to neural activation in the cingulate cortex during emotion processing.

48 healthy subjects underwent an fMRI paradigm comprising emotional (angry/fearful faces and scenes) and neutral stimuli (simple shapes). 5-HT Vmax was determined in platelets. Subjects were genotyped for a common triallelic polymorphism in the promoter region of the 5-HTT gene (5-HTTLPR).

Significant negative correlations between Vmax and BOLD-signal in the anterior and posterior portion of the cingulate cortex have been found. Cluster maxima within both regions were detected in the subgenual anterior cortex (−1.5, 28.5, −3.5, t = −3.77) and the ventral posterior cingulate cortex (−4.5, −49.5,14.5, t = −3.06). Genotype did not impact on this relationship.

Our results indicate a clear dependency between a peripheral marker, platelet 5-HT uptake velocity, and neural activity in portions of the cingulate cortex for the first time.