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.
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Acknowledgements
This research was supported by the Intramural Research Program of the NIMH. JPR was supported by the NIH-Cambridge Health Science Scholars Program. We thank Judy Starling for preparation of the amino acid mixtures, Mike Franklin for analysis of the plasma amino acids, Harvey Iwamoto for programming the AGNG, Rebecca Elliott, and Judy Rubinsztein for kindly providing the original word lists for the AGNG, Jeanette Black and Renee Hill for radiographer support, the nurses of ward 5 South-West for their dedicated clinical support, Karl Friston for guidance regarding fMRI analysis and Predrag Petrovic for helpful discussion of the manuscript. We thank Joan Williams and Paul Carlson for help with recruitment and clinical support. Finally, we would like to thank all the volunteers who participated in this study.
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The authors declare that over the past 3 years JPR and BJS have received compensation for consultancy work from Cambridge Cognition Ltd, who now own the behavioral version of the AGNG.
JPR has received compensation from Cambridge University.
GH has received compensation from Fundacion Lilly, Spain.
WCD has received compensation from Saint Vincent Catholic Medical Centers, the University of Maryland, Imedex, IntraMed Educational Group, CME Incorporated, Pfizer Inc./Medcon, the Neuroscience Education Institute, the Society of Nuclear Medicine, the American Neuropsychiatric Association, Carroll Hospital, Wisconsin Medical School/Current Medical Direction Inc., the Foundation for Advanced Education in the Sciences, Carilion Health Systems, Roanoke VA, the Medical College of Ohio, Mt. Sinai School of Medicine, Washington University, St Louis University, the Karolinska Institute, Laureate Psychiatric Clinic and Hospital (Tulsa), Assistance Publique, Hopitaux de Paris (sponsored by unrestricted educational grant from Servier), Photosound/Mind Matters (sponsored by unrestricted educational grant from Sanofi-Aventis), the University of California at San Diego, the Neuroscience Center, Zurich, of the University of Zurich, Zurich Switzerland.
BJS has received compensation from Massachusetts General Hospital, the International Conference on Cognitive Dysfunction in Schizophrenia and Mood Disorders, the Medical Research Council Neurosciences & Mental Health Board, the Science Co-ordination Team for the Foresight Project on Mental Capital and Wellbeing (Office of Science and Innovation, Department of Trade and Industry), and the journal Psychological Medicine.
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Roiser, J., Levy, J., Fromm, S. et al. The Effect of Acute Tryptophan Depletion on the Neural Correlates of Emotional Processing in Healthy Volunteers. Neuropsychopharmacol 33, 1992–2006 (2008). https://doi.org/10.1038/sj.npp.1301581
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DOI: https://doi.org/10.1038/sj.npp.1301581
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