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Converging evidence for central 5-HT effects in acute tryptophan depletion

Molecular Psychiatry volume 17, pages 121–123 (2012)Cite this article

A Corrigendum to this article was published on 26 March 2012

Acute tryptophan depletion (ATD), a dietary technique for manipulating brain serotonin (5-HT) function, has advanced our understanding of 5-HT mechanisms in the etiology and treatment of depression and other affective disorders.1 A recent review article in Molecular Psychiatry questioned the validity of ATD.2 Although we agree that ATD's effects on 5-HT activity at the molecular level need further clarification, van Donkelaar et al.2 goes too far in challenging whether ATD exerts its effects through serotonergic mechanisms. There is strong evidence that ATD reduces brain 5-HT and disrupts stimulated 5-HT release,3, 4 and converging translational findings support a central role for brain 5-HT in ATD's effects on cognition and behavior.5, 6, 7

Van Donkelaar et al.2 does not dispute the fact that ATD reduces 5-HT synthesis and brain 5-HT levels.4 Their arguments converge on two issues. First, they claim that non-serotonergic mechanisms could explain ATD effects, including altered peripheral metabolic processes, cerebrovascular abnormalities and confounding stress effects. Although we welcome additional research to explore these complex alternative pathways, the most parsimonious explanation of ATD's effects on human cognition and behavior is that ATD influences central 5-HT function. ATD has produced results paralleling those following other 5-HT manipulations in humans and animals. For example, ATD has reliable and highly selective effects on emotional processing in humans, inducing a cognitive bias toward negative stimuli and away from positive stimuli.5 In line with these findings, a recent translational study comparing the effects of citalopram and neurotoxin-induced global 5-HT depletions in rats showed that reducing 5-HT function increased sensitivity to negative stimuli and reduced sensitivity to positive stimuli, whereas enhancing 5-HT function had the opposite effect.6 Many other equivalent examples abound.7 These converging findings have been replicated across different laboratories, and support a primary role for brain 5-HT in mediating the effects of ATD.

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Authors and Affiliations

  1. Behavioural and Clinical Neuroscience Institute, Cambridge, UK

    M J Crockett, A Apergis-Schoute, B J Sahakian & T W Robbins

  2. Department of Experimental Psychology, University of Cambridge, Cambridge, UK

    M J Crockett, L Clark, A Apergis-Schoute & T W Robbins

  3. Institute of Cognitive Neuroscience, University College London, London, UK

    J P Roiser

  4. Mood and Anxiety Disorders Program, NIMH, Bethesda, MD, USA

    O J Robinson

  5. Centre for Cognitive Neuroimaging and Department of Psychiatry, Radboud University Nijmegen, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands

    R Cools & H den Ouden

  6. Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    H W Chase

  7. CFIN, Aarhus University, Aarhus, Denmark

    D Campbell-Meikeljohn

  8. Wellome Trust Centre for Neuroimaging, University College London, London, UK

    B Seymour

  9. Department of Psychiatry, University of Cambridge, Cambridge, UK

    B J Sahakian

  10. Departments of Psychiatry and Experimental Psychology, University of Oxford, Oxford, UK

    R D Rogers

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  1. M J Crockett
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  2. L Clark
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Correspondence to M J Crockett.

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Crockett, M., Clark, L., Roiser, J. et al. Converging evidence for central 5-HT effects in acute tryptophan depletion. Mol Psychiatry 17, 121–123 (2012). https://doi.org/10.1038/mp.2011.106

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