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Neuropsychopharmacology. 2008 Jul;33(8):1992-2006. Epub 2007 Sep 19.

The effect of acute tryptophan depletion on the neural correlates of emotional processing in healthy volunteers.

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Department of Imaging Neuroscience, Institute of Neurology, London, UK.


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.

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