title: Presynaptic Serotoninergic Regulation of Emotional Processing: A Multimodal Brain Imaging Study.
abstract: 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 [(11)C]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.
authors.affiliation: Medical Research Council Clinical Sciences Centre, Hammersmith Hospital, London, W12 0NN, UK.|Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at Houston, Houston, TX, USA.
authors.forename: Sudhakar
authors.initials: S
authors.lastname: Selvaraj
authors.affiliation: Medical Research Council Clinical Sciences Centre, Hammersmith Hospital, London, W12 0NN, UK.
authors.forename: Elias
authors.initials: E
authors.lastname: Mouchlianitis
authors.affiliation: Institute of Cognitive Neuroscience, University College London, WC1N 3AR, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Faulkner
authors.affiliation: Institute of Psychiatry, King's College London, SE5 8AF, UK.
authors.forename: Federico
authors.initials: F
authors.lastname: Turkheimer
authors.affiliation: Department of Psychiatry, University of Oxford, OX3 7JX, UK.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Cowen
authors.affiliation: Institute of Cognitive Neuroscience, University College London, WC1N 3AR, UK.
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Roiser
authors.affiliation: Medical Research Council Clinical Sciences Centre, Hammersmith Hospital, London, W12 0NN, UK.|Institute of Psychiatry, King's College London, SE5 8AF, UK.
authors.forename: Oliver
authors.initials: O
authors.lastname: Howes
mesh_terms: D000328:Adult; D000679:Amygdala / Q000503:physiopathology*; D004644:Emotions / Q000502:physiology*; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism*; D006179:Gyrus Cinguli / Q000378:metabolism*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010296:Parietal Lobe / Q000378:metabolism*; D049268:Positron-Emission Tomography; D011603:Psychophysiology; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*
chemical_list: D044282:Receptor, Serotonin, 5-HT1A
keywords: 5-HT(1A) receptor; Amygdala; Dorsal raphe nucleus; Emotion; Face processing; Functional connectivity; Functional magnetic resonance imaging; Neuroimaging; Positron emission tomography (PET); Serotonin (5-HT); [(11)C]CUMI-101