1. ¹Department of Imaging Neuroscience, Institute of Neurology, London, UK
2. ²Section on Neuroimaging in Mood and Anxiety Disorders, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA
3. ³Department of Psychiatry, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK

Correspondence: Dr JP Roiser, Department of Imaging Neuroscience, Institute of Neurology, Room 807, Queen Square House, London WC1N 3BG, UK. Tel: +44 207 837 3611 x4271; Fax: +44 207 676 2051; E-mail: j.roiser@ion.ucl.ac.uk

Received 24 May 2007; Revised 16 August 2007; Accepted 17 August 2007; Published online 19 September 2007.

Abstract

The processing of affective material is known to be modulated by serotonin (5-HT), but few studies have used neurophysiological measures to characterize the effect of changes in 5-HT on neural responses to emotional stimuli. We used functional magnetic resonance imaging to investigate the effect of acute tryptophan depletion, which reduces central 5-HT synthesis, on neural responses to emotionally valenced verbal stimuli. Though no participants experienced significant mood change, emotional information processing was substantially modified following 5-HT depletion. A behavioral bias toward positive stimuli was attenuated following depletion, which was accompanied by increased hemodynamic responses during the processing of emotional words in several subcortical structures. Inter-individual differences in tryptophan depletion-elicited anxiety correlated positively with the caudate bias toward negative stimuli. These data suggest that 5-HT may play an important role in mediating automatic negative attentional biases in major depression, as well as resilience against negative distracting stimuli in never-depressed individuals.