Presynaptic serotoninergic regulation of emotional processing: A multimodal brain imaging study
Selvaraj S., Mouchlianitis E., Faulkner P., Turkheimer F., Cowen PJ., Roiser JP., Howes O.
© 2015 Society of Biological Psychiatry. Background The amygdala is a central node in the brain network that processes aversive emotions and is extensively innervated by dorsal raphe nucleus (DRN) serotonin (5-hydroxytryptamine [5-HT]) neurons. Alterations in DRN 5-HT < inf > 1A < /inf > receptor availability cause phenotypes characterized by fearful behavior in preclinical models. However, it is unknown whether 5-HT < inf > 1A < /inf > receptor availability is linked specifically to the processing of aversive emotions in humans or whether it modulates connectivity in brain networks involved in emotion processing. To answer this question, we investigated the relationship between DRN 5-HT < inf > 1A < /inf > receptor availability and amygdala reactivity to aversive emotion and functional connectivity within the amygdala-cortical network. Methods We studied 15 healthy human participants who underwent positron emission tomography scanning with [ < sup > 11 < /sup > C]CUMI-101, a 5-HT < inf > 1A < /inf > partial agonist radioligand, and functional magnetic resonance imaging of brain responses during an incidental emotion processing task including happy, fearful, and neutral faces. Regional estimates of 5-HT < inf > 1A < /inf > receptor binding potential (nondisplaceable) were obtained by calculating total volumes of distribution for presynaptic DRN and amygdala. Connectivity between the amygdala and corticolimbic areas was assessed using psychophysiologic interaction analysis with the amygdala as the seed region. Results Analysis of the fear versus neutral contrast revealed a significant negative correlation between amygdala response and DRN binding potential (nondisplaceable) (r = -.87, p < .001). Availability of DRN 5-HT < inf > 1A < /inf > receptors positively correlated with amygdala connectivity with middle frontal gyrus, anterior cingulate cortex, bilateral precuneus, and left supramarginal gyrus for fearful (relative to neutral) faces. Conclusions Our data show that DRN 5-HT < inf > 1A < /inf > receptor availability is linked specifically to the processing of aversive emotions in the amygdala and the modulation of amygdala-cortical connectivity.