title: Fluctuations in [¹¹C]SB207145 PET binding associated with change in threat-related amygdala reactivity in humans.
abstract: Serotonin critically affects the neural processing of emotionally salient stimuli, including indices of threat; however, how alterations in serotonin signaling contribute to changes in brain function is not well understood. Recently, we showed in a placebo-controlled study of 32 healthy males that brain serotonin 4 receptor (5-HT4) binding, assessed with [(11)C]SB207145 PET, was sensitive to a 3-week intervention with the selective serotonin reuptake inhibitor fluoxetine, supporting it as an in vivo model for fluctuations in central serotonin levels. Participants also underwent functional magnetic resonance imaging while performing a gender discrimination task of fearful, angry, and neutral faces. This offered a unique opportunity to evaluate whether individual fluctuations in central serotonin levels, indexed by change in [(11)C]SB207145 binding, predicted changes in threat-related reactivity (ie, fear and angry vs neutral faces) within a corticolimbic circuit including the amygdala and medial prefrontal and anterior cingulate cortex. We observed a significant association such that decreased brain-wide [(11)C]SB207145 binding (ie, increased brain serotonin levels) was associated with lower threat-related amygdala reactivity, whereas intervention group status did not predict change in corticolimbic reactivity. This suggests that in the healthy brain, interindividual responses to pharmacologically induced and spontaneously occurring fluctuations in [(11)C]SB207145 binding, a putative marker of brain serotonin levels, affect amygdala reactivity to threat. Our finding also supports that change in brain [(11)C]SB207145 binding may be a relevant marker for evaluating neurobiological mechanisms underlying sensitivity to threat and serotonin signaling.
authors.affiliation: 1] Center for Integrated Molecular Brain Imaging, Copenhagen University Hospital Rigshospitalet, Copenhagen O, Denmark [2] Neurobiology Research Unit, Copenhagen University Hospital Rigshospitalet, Copenhagen O, Denmark.
authors.forename: Patrick MacDonald
authors.initials: PM
authors.lastname: Fisher
authors.affiliation: 1] Center for Integrated Molecular Brain Imaging, Copenhagen University Hospital Rigshospitalet, Copenhagen O, Denmark [2] Neurobiology Research Unit, Copenhagen University Hospital Rigshospitalet, Copenhagen O, Denmark.
authors.forename: Mette Ewers
authors.initials: ME
authors.lastname: Haahr
authors.affiliation: 1] Center for Integrated Molecular Brain Imaging, Copenhagen University Hospital Rigshospitalet, Copenhagen O, Denmark [2] Neurobiology Research Unit, Copenhagen University Hospital Rigshospitalet, Copenhagen O, Denmark.
authors.forename: Christian Gaden
authors.initials: CG
authors.lastname: Jensen
authors.affiliation: 1] Center for Integrated Molecular Brain Imaging, Copenhagen University Hospital Rigshospitalet, Copenhagen O, Denmark [2] Neurobiology Research Unit, Copenhagen University Hospital Rigshospitalet, Copenhagen O, Denmark.
authors.forename: Vibe Gedsoe
authors.initials: VG
authors.lastname: Frokjaer
authors.affiliation: 1] Center for Integrated Molecular Brain Imaging, Copenhagen University Hospital Rigshospitalet, Copenhagen O, Denmark [2] Danish Research Centre for Magnetic Resonance, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark [3] Department of Neurology, Copenhagen University Hospital Bispebjerg, Copenhagen NV, Denmark.
authors.forename: Hartwig Roman
authors.initials: HR
authors.lastname: Siebner
authors.affiliation: 1] Center for Integrated Molecular Brain Imaging, Copenhagen University Hospital Rigshospitalet, Copenhagen O, Denmark [2] Neurobiology Research Unit, Copenhagen University Hospital Rigshospitalet, Copenhagen O, Denmark.
authors.forename: Gitte Moos
authors.initials: GM
authors.lastname: Knudsen
mesh_terms: D000328:Adult; D000679:Amygdala / Q000000981:diagnostic imaging* / Q000502:physiology*; D001931:Brain Mapping; D004311:Double-Blind Method; D005239:Fear / Q000502:physiology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D010551:Personality; D010880:Piperidines; D049268:Positron-Emission Tomography; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging / Q000502:physiology; D019275:Radiopharmaceuticals; D012701:Serotonin / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics
chemical_list: D010880:Piperidines; D019275:Radiopharmaceuticals; C534709:SB 207145; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin