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Stop signal response inhibition is not modulated by tryptophan depletion or the serotonin transporter polymorphism in healthy volunteers: implications for the 5-HT theory of impulsivity

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Abstract

Rationale

Reduced serotonin neurotransmission is implicated in disorders of impulse control, but the involvement of serotonin in inhibitory processes in healthy human subjects remains unclear.

Objectives

To investigate the effects of an acute manipulation of serotonin and genotype at a functional polymorphism in a gene coding for the serotonin transporter (5-HTT) on an established measure of response inhibition.

Methods

Serotonin function was reduced by the acute tryptophan depletion (ATD) procedure in a double-blind, crossover design in 42 healthy subjects. The Stop Signal Task (SST) was administered 5–7 h after drink administration. The influences of 5-HTT polymorphism, gender and trait impulsivity were investigated.

Results

ATD was associated with significant depletion of plasma tryptophan levels but did not increase the stop signal reaction time in comparison to the balanced (placebo) amino acid mixture. Subjects possessing the short allele of the 5-HTT polymorphism were not more impulsive on the SST than subjects homozygous for the long allele under placebo conditions and were not disproportionately sensitive to the effects of ATD. There was no effect of gender or trait impulsivity on ATD-induced change.

Conclusions

We find no support for the involvement of brain serotonin neurotransmission in this form of inhibitory control in healthy human subjects.

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Acknowledgements

This work was supported by a Wellcome Trust programme grant to T.W.R., B.J.S., B.J. Everitt and A.C. Roberts and completed within the MRC Centre for Behavioural and Clinical Neuroscience. All testing was conducted at the Wellcome Trust Clinical Research Facility at Addenbrooke's Hospital, Cambridge. D.C.R. is a Wellcome Trust Senior Fellow in Clinical Science. We wish to thank Dr. M. Franklin and Dr. J. Odontiadis (University of Oxford) for analysis of plasma data, Dr. J. Whitaker for DNA extraction and Dr. A. Aron for programming assistance and helpful comments on the manuscript. This article was presented as a poster at the Cognitive Neuroscience Society annual meeting in New York, April 10–12, 2005.

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Authors and Affiliations

  1. Department of Experimental Psychology, University of Cambridge, Downing Street, Cambridge, UK

    L. Clark, R. Cools & T. W. Robbins

  2. Department of Psychiatry, University of Cambridge School of Clinical Medicine, Cambridge, UK

    J. P. Roiser & B. J. Sahakian

  3. National Institutes of Mental Health, Section on Mood and Anxiety Disorders, Bethesda, MD, 20852, USA

    J. P. Roiser

  4. Helen Wills Neuroscience Institute, University of California, Berkeley, CA, 94720, USA

    R. Cools

  5. Department of Medical Genetics, Cambridge Institute for Medical Research, Wellcome Trust/MRC Building, Addenbrooke's Hospital, Cambridge, UK

    D. C. Rubinsztein

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  1. L. Clark
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  2. J. P. Roiser
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  3. R. Cools
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  4. D. C. Rubinsztein
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  5. B. J. Sahakian
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  6. T. W. Robbins
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Correspondence to L. Clark.

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Clark, L., Roiser, J.P., Cools, R. et al. Stop signal response inhibition is not modulated by tryptophan depletion or the serotonin transporter polymorphism in healthy volunteers: implications for the 5-HT theory of impulsivity. Psychopharmacology 182, 570–578 (2005). https://doi.org/10.1007/s00213-005-0104-6

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  • DOI: https://doi.org/10.1007/s00213-005-0104-6

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