TY - JOUR
T1 - Presynaptic serotoninergic regulation of emotional processing
T2 - A multimodal brain imaging study
AU - Selvaraj, Sudhakar
AU - Mouchlianitis, Elias
AU - Faulkner, Paul
AU - Turkheimer, Federico
AU - Cowen, Philip J.
AU - Roiser, Jonathan P.
AU - Howes, Oliver
N1 - Funding Information:
This work was supported by the Medical Research Council, United Kingdom.
Publisher Copyright:
© 2015 Society of Biological Psychiatry.
PY - 2015/10/15
Y1 - 2015/10/15
N2 - 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-HT1A receptor availability cause phenotypes characterized by fearful behavior in preclinical models. However, it is unknown whether 5-HT1A 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-HT1A 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 [11C]CUMI-101, a 5-HT1A 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-HT1A 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-HT1A 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-HT1A receptor availability is linked specifically to the processing of aversive emotions in the amygdala and the modulation of amygdala-cortical connectivity.
AB - 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-HT1A receptor availability cause phenotypes characterized by fearful behavior in preclinical models. However, it is unknown whether 5-HT1A 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-HT1A 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 [11C]CUMI-101, a 5-HT1A 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-HT1A 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-HT1A 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-HT1A receptor availability is linked specifically to the processing of aversive emotions in the amygdala and the modulation of amygdala-cortical connectivity.
KW - 5-HT receptor
KW - Amygdala
KW - Dorsal raphe nucleus
KW - Emotion
KW - Face processing
KW - Functional connectivity
KW - Functional magnetic resonance imaging
KW - Neuroimaging
KW - Positron emission tomography (PET)
KW - Serotonin (5-HT)
KW - [C]CUMI-101
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U2 - 10.1016/j.biopsych.2014.04.011
DO - 10.1016/j.biopsych.2014.04.011
M3 - Article
C2 - 24882568
AN - SCOPUS:84941801837
SN - 0006-3223
VL - 78
SP - 563
EP - 571
JO - Biological Psychiatry
JF - Biological Psychiatry
IS - 8
ER -