Archival Report| Volume 66, ISSUE 5, P441-450, September 01, 2009

The Effects of Tryptophan Depletion on Neural Responses to Emotional Words in Remitted Depression

  • Jonathan P. Roiser
    Address correspondence to Jonathan P. Roiser, Ph.D., University College London, Institute of Cognitive Neuroscience, 17 Queen Square, London WC1N 3AR, United Kingdom
    Institute of Cognitive Neuroscience, University College London, London, United Kingdom

    Section on Neuroimaging in Mood and Anxiety Disorders, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland

    Department of Psychiatry, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom
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  • Jamey Levy
    Section on Neuroimaging in Mood and Anxiety Disorders, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland
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  • Stephen J. Fromm
    Section on Neuroimaging in Mood and Anxiety Disorders, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland
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  • Allison C. Nugent
    Section on Neuroimaging in Mood and Anxiety Disorders, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland
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  • S. Lalith Talagala
    National Institutes of Health MRI Research Facility, National Institute of Neurological Disorders and Stroke, Bethesda, Maryland
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  • Gregor Hasler
    Section on Neuroimaging in Mood and Anxiety Disorders, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland
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  • Fritz A. Henn
    Brookhaven National Laboratory, Upton, New York
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  • Barbara J. Sahakian
    Department of Psychiatry, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom

    Medical Research Council/Wellcome Trust Behavioral and Clinical Neuroscience Institute, Cambridge, United Kingdom
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  • Wayne C. Drevets
    Section on Neuroimaging in Mood and Anxiety Disorders, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland
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      Major depressive disorder (MDD) has been associated with both dysfunction of the central serotonergic system and abnormal responses to emotional stimuli. We used acute tryptophan depletion (ATD) to investigate the effect of temporarily reducing brain serotonin synthesis on neural and behavioral responses to emotional stimuli in remitted MDD subjects (rMDD) and healthy control subjects.


      Twenty control subjects and 23 rMDD subjects who had been unmedicated and in remission for ≥3 months completed the study. Following tryptophan or sham depletion, participants performed an emotional-processing task during functional magnetic resonance imaging. In addition, resting state regional blood flow was measured using arterial spin labeling.


      Neither group exhibited significant mood change following ATD. However, tryptophan depletion differentially affected the groups in terms of hemodynamic responses to emotional words in a number of structures implicated in the pathophysiology of MDD, including medial thalamus and caudate. These interactions were driven by increased responses to emotional words in the control subjects, with little effect in the patients under the ATD condition. Following ATD, habenula blood flow increased significantly in the rMDD subjects relative to the control subjects, and increasing amygdala blood flow was associated with more negative emotional bias score across both groups.


      These data provide evidence for elevated habenula blood flow and alterations in the neural processing of emotional stimuli following ATD in rMDD subjects, even in the absence of overt mood change. However, further studies are required to determine whether these findings represent mechanisms of resilience or vulnerability to MDD.

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