title: Threat-related amygdala functional connectivity is associated with 5-HTTLPR genotype and neuroticism.
abstract: Communication between the amygdala and other brain regions critically regulates sensitivity to threat, which has been associated with risk for mood and affective disorders. The extent to which these neural pathways are genetically determined or correlate with risk-related personality measures is not fully understood. Using functional magnetic resonance imaging, we evaluated independent and interactive effects of the 5-HTTLPR genotype and neuroticism on amygdala functional connectivity during an emotional faces paradigm in 76 healthy individuals. Functional connectivity between left amygdala and medial prefrontal cortex (mPFC) and between both amygdalae and a cluster including posterior cingulate cortex, precuneus and visual cortex was significantly increased in 5-HTTLPR S' allele carriers relative to L(A)L(A) individuals. Neuroticism was negatively correlated with functional connectivity between right amygdala and mPFC and visual cortex, and between both amygdalae and left lateral orbitofrontal (lOFC) and ventrolateral prefrontal cortex (vlPFC). Notably, 5-HTTLPR moderated the association between neuroticism and functional connectivity between both amygdalae and left lOFC/vlPFC, such that S' carriers exhibited a more negative association relative to L(A)L(A) individuals. These findings provide novel evidence for both independent and interactive effects of 5-HTTLPR genotype and neuroticism on amygdala communication, which may mediate effects on risk for mood and affective disorders.
authors.affiliation: Neurobiology Research Unit and Center for Integrated Molecular Brain Imaging, Copenhagen University Hospital Rigshospitalet, 2100 Copenhagen O, Denmark.
authors.forename: Martin Korsbak
authors.initials: MK
authors.lastname: Madsen
authors.affiliation: Neurobiology Research Unit and Center for Integrated Molecular Brain Imaging, Copenhagen University Hospital Rigshospitalet, 2100 Copenhagen O, Denmark.
authors.forename: Brenda
authors.initials: B
authors.lastname: Mc Mahon
authors.affiliation: Neurobiology Research Unit and Center for Integrated Molecular Brain Imaging, Copenhagen University Hospital Rigshospitalet, 2100 Copenhagen O, Denmark.
authors.forename: Sofie Bech
authors.initials: SB
authors.lastname: Andersen
authors.affiliation: Center for Integrated Molecular Brain Imaging, Copenhagen University Hospital Rigshospitalet, 2100 Copenhagen O, Denmark, Danish Research Centre for Magnetic Resonance, Copenhagen University Hospital Hvidovre, 2650 Hvidovre, Denmark, and Department of Neurology, Copenhagen University Hospital Bispebjerg, 2400 Copenhagen NW, Denmark.
authors.forename: Hartwig Roman
authors.initials: HR
authors.lastname: Siebner
authors.affiliation: Neurobiology Research Unit and Center for Integrated Molecular Brain Imaging, Copenhagen University Hospital Rigshospitalet, 2100 Copenhagen O, Denmark, gmk@nru.dk.
authors.forename: Gitte Moos
authors.initials: GM
authors.lastname: Knudsen
authors.affiliation: Neurobiology Research Unit and Center for Integrated Molecular Brain Imaging, Copenhagen University Hospital Rigshospitalet, 2100 Copenhagen O, Denmark.
authors.forename: Patrick MacDonald
authors.initials: PM
authors.lastname: Fisher
mesh_terms: D000293:Adolescent; D000328:Adult; D000679:Amygdala / Q000502:physiology* / Q000503:physiopathology*; D001008:Anxiety Disorders / Q000235:genetics* / Q000503:physiopathology*; D001143:Arousal / Q000502:physiology*; D001921:Brain / Q000503:physiopathology; D004644:Emotions / Q000502:physiology*; D005260:Female; D005838:Genotype; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009434:Neural Pathways / Q000503:physiopathology; D000075384:Neuroticism; D017397:Prefrontal Cortex / Q000503:physiopathology; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D055815:Young Adult
chemical_list: C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins
keywords: 5-HTTLPR; amygdala; fMRI; functional connectivity; neuroticism; prefrontal cortex