Human 5-HT transporter availability predicts amygdala reactivity in vivo.
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.
Rhodes
Rebecca A
RA
Psychiatry Group, Medical Research Council Clinical Sciences Centre, London W12 0NN, United Kingdom.
Murthy
Naga Venkatesha
NV
Dresner
M Alex
MA
Selvaraj
Sudhakar
S
Stavrakakis
Nikolaos
N
Babar
Syed
S
Cowen
Philip J
PJ
Grasby
Paul M
PM
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*
D001596:Benzylamines; D002247:Carbon Isotopes; C420885:N,N-dimethyl-2-(2-amino-4-cyanophenylthio)benzylamine; D050486:Serotonin Plasma Membrane Transport Proteins; D010100:Oxygen
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