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The Journal of Neuroscience, August 22, 2007, 27(34):9233-9237; doi:10.1523/JNEUROSCI.1175-07.2007

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Brief Communications
Human 5-HT Transporter Availability Predicts Amygdala Reactivity In Vivo

Rebecca A. Rhodes,¹ Naga Venkatesha Murthy,^1,3 M. Alex Dresner,² Sudhakar Selvaraj,^1,4 Nikolaos Stavrakakis,¹ Syed Babar,⁵ Philip J. Cowen,⁴ and Paul M. Grasby¹

¹Psychiatry Group, ²Imaging Sciences Department, Medical Research Council (MRC) Clinical Sciences Centre, and ³Experimental Medicine, Psychiatry Clinical Pharmaceology Discovery Medicine, GlaxoSmithKline Clinical Imaging Centre, Imperial College London, London W12 0NN, United Kingdom, ⁴Department of Psychiatry, University of Oxford, Oxford OX3 7JX, United Kingdom, and ⁵Radiology Department, Hammersmith Hospital, London W12 0HS, United Kingdom

Correspondence should be addressed to Prof. Paul M. Grasby, Psychiatry Group, Medical Research Council Clinical Sciences Centre, Imperial College, Hammersmith Hospital campus, Du Cane Road, London W12 0NN, UK. Email: paul.grasby{at}imperial.ac.uk

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 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.

Key words: 5-HTT; imaging; [¹¹C]-DASB; PET; fMRI; amygdala; emotion

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Received March 15, 2007; revised June 21, 2007; accepted July 5, 2007.

Correspondence should be addressed to Prof. Paul M. Grasby, Psychiatry Group, Medical Research Council Clinical Sciences Centre, Imperial College, Hammersmith Hospital campus, Du Cane Road, London W12 0NN, UK. Email: paul.grasby{at}imperial.ac.uk

This article has been cited by other articles:

				B. A. Strange, M. C. W. Kroes, J. P. Roiser, G. C. Y. Tan, and R. J. Dolan Emotion-Induced Retrograde Amnesia Is Determined by a 5-HTT Genetic Polymorphism J. Neurosci., July 9, 2008; 28(28): 7036 - 7039. [Abstract] [Full Text] [PDF]

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