title: Human 5-HT transporter availability predicts amygdala reactivity in vivo.
abstract: The amygdala plays a central role in fear conditioning, emotional processing, and memory modulation. A postulated key component of the neurochemical regulation of amygdala function is the neurotransmitter 5-hydroxytryptamine (5-HT), and synaptic levels of 5-HT in the amygdala and elsewhere are critically regulated by the 5-HT transporter (5-HTT). The aim of this study was to directly examine the relationship between 5-HTT availability and amygdala activity using multimodal [positron emission tomography (PET) and functional magnetic resonance imaging (fMRI)] imaging measures in the same individuals. Healthy male volunteers who had previously undergone an [11C]-3-amino-4-(2-dimethylaminomethylphenylsulfanyl)-benzonitrile ([11C]-DASB) PET scan to determine 5-HTT availability completed an fMRI emotion recognition task. [11C]-DASB binding potential values were calculated for the amygdala using arterial input function and linear graphical (Logan) analysis. fMRI was performed on a 3T Philips Intera scanner, and data were analyzed using SPM2 (Wellcome Department Imaging Neuroscience, University College London). Percentage signal change during the task was extracted from the amygdala using MarsBaR (Brett et al., 2002). fMRI analysis revealed significant amygdala activation during the emotion recognition task. Region of interest analyses demonstrated a significant negative correlation between fMRI signal change in the left amygdala and 5-HTT availability in the left amygdala, with 5-HTT availability accounting for approximately 42% of the variability in left amygdala activity. Our novel in vivo data highlight the central importance of the serotonergic system in the responsiveness of the human amygdala during emotional processing.
authors: Psychiatry Group, Medical Research Council Clinical Sciences Centre, London W12 0NN, United Kingdom.
authors: Rebecca A
authors: RA
authors: Rhodes
authors: Naga Venkatesha
authors: NV
authors: Murthy
authors: M Alex
authors: MA
authors: Dresner
authors: Sudhakar
authors: S
authors: Selvaraj
authors: Nikolaos
authors: N
authors: Stavrakakis
authors: Syed
authors: S
authors: Babar
authors: Philip J
authors: PJ
authors: Cowen
authors: Paul M
authors: PM
authors: Grasby
mesh_terms: D000328:Adult; D000679:Amygdala / Q000098:blood supply / Q000000981:diagnostic imaging / Q000187:drug effects / Q000502:physiology*; D001596:Benzylamines / Q000493:pharmacokinetics; D002247:Carbon Isotopes / Q000493:pharmacokinetics; D004644:Emotions / Q000502:physiology; D005260:Female; D007839:Functional Laterality; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D010100:Oxygen / Q000097:blood; D049268:Positron-Emission Tomography / Q000379:methods; D011237:Predictive Value of Tests; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*
chemical_list: D001596:Benzylamines; D002247:Carbon Isotopes; C420885:N,N-dimethyl-2-(2-amino-4-cyanophenylthio)benzylamine; D050486:Serotonin Plasma Membrane Transport Proteins; D010100:Oxygen
references: Biol Psychiatry. 2000 May 1;47(9):769-76
references: 10812035
references: J Med Chem. 2000 Aug 10;43(16):3103-10
references: 10956218
references: Neuroreport. 2001 Aug 8;12(11):2543-7
references: 11496145
references: Arch Gen Psychiatry. 2001 Nov;58(11):1057-63
references: 11695953
references: J Cereb Blood Flow Metab. 2001 Nov;21(11):1342-53
references: 11702049
references: Biol Psychiatry. 2001 Nov 1;50(9):651-8
references: 11704071
references: Curr Opin Neurobiol. 2002 Apr;12(2):169-77
references: 12015233
references: Life Sci. 2002 Jul 5;71(7):751-7
references: 12074934
references: Arch Gen Psychiatry. 2002 Nov;59(11):1027-34
references: 12418936
references: Hum Brain Mapp. 2003 Aug;19(4):224-47
references: 12874777
references: Neurosci Lett. 2003 Sep 4;348(1):41-5
references: 12893421
references: Neuropsychopharmacology. 2003 Dec;28(12):2077-88
references: 12968128
references: J Nucl Med. 2004 Apr;45(4):682-94
references: 15073266
references: Brain Res Brain Res Rev. 2004 May;45(2):96-103
references: 15145620
references: Arch Gen Psychiatry. 2004 Sep;61(9):877-89
references: 15351766
references: Arch Gen Psychiatry. 2004 Dec;61(12):1271-9
references: 15583118
references: Arch Gen Psychiatry. 2005 Feb;62(2):146-52
references: 15699291
references: Neuropsychopharmacology. 2005 Sep;30(9):1724-34
references: 15827569
references: Neuroimage. 2005 May 1;25(4):1112-23
references: 15850729
references: Biol Psychiatry. 2006 Mar 1;59(5):424-9
references: 16256956
references: Biol Psychiatry. 2006 Sep 1;60(5):479-90
references: 16414028
references: Biol Psychiatry. 2006 May 1;59(9):816-20
references: 16460693
references: J Nucl Med. 2006 May;47(5):815-26
references: 16644752
references: J Neurosci. 2006 Aug 30;26(35):8955-64
references: 16943551
references: Nat Neurosci. 2006 Nov;9(11):1362-3
references: 17013380
references: Am J Psychiatry. 2007 Dec;164(12):1858-65
references: 18056241
references: J Cereb Blood Flow Metab. 1990 Sep;10(5):740-7
references: 2384545
references: Ann Neurol. 1984 Mar;15(3):217-27
references: 6609679
references: Life Sci. 1994;55(3):163-7
references: 8007758
references: Science. 1996 Nov 29;274(5292):1527-31
references: 8929413