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Effects of risperidone, amisulpride and nicotine on eye movement control and their modulation by schizotypy

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Abstract

Rationale

The increasing demand to develop more efficient compounds to treat cognitive impairments in schizophrenia has led to the development of experimental model systems. One such model system combines the study of surrogate populations expressing high levels of schizotypy with oculomotor biomarkers.

Objectives

We aimed (1) to replicate oculomotor deficits in a psychometric schizotypy sample and (2) to investigate whether the expected deficits can be remedied by compounds shown to ameliorate impairments in schizophrenia.

Methods

In this randomized double-blind, placebo-controlled study 233 healthy participants performed prosaccade (PS), antisaccade (AS) and smooth pursuit eye movement (SPEM) tasks after being randomly assigned to one of four drug groups (nicotine, risperidone, amisulpride, placebo). Participants were classified into medium- and high-schizotypy groups based on their scores on the Schizotypal Personality Questionnaire (SPQ, Raine (Schizophr Bull 17:555–564, 1991)).

Results

AS error rate showed a main effect of Drug (p < 0.01), with nicotine improving performance, and a Drug by Schizotypy interaction (p = 0.04), indicating higher error rates in medium schizotypes (p = 0.01) but not high schizotypes under risperidone compared to placebo. High schizotypes had higher error rates than medium schizotypes under placebo (p = 0.03). There was a main effect of Drug for saccadic peak velocity and SPEM velocity gain (both p ≤ 0.01) indicating impaired performance with risperidone.

Conclusions

We replicate the observation of AS impairments in high schizotypy under placebo and show that nicotine enhances performance irrespective of group status. Caution should be exerted in applying this model as no beneficial effects of antipsychotics were seen in high schizotypes.

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Acknowledgments

We would like to thank the participating volunteers and all research staff and students who helped collecting the data. The experiments carried out in this study comply with the current laws of the country in which they were performed

Disclosure/conflicts of interest

This study was supported by the P1vital CNS Experimental Medicine Consortium (members AstraZeneca, GlaxoSmithKline, Lundbeck, Organon (a subsidiary of Merck) and Pfizer). The PhD of Anne Schmechtig and Katrina McMullen were partly funded by P1vital CNS Experimental Medicine Consortium. Ivan Koychev has been awarded a Manchester Strategic PhD Studentship, sponsored by the University of Manchester and P1vital Ltd. John Francis William Deakin has been supported by the Manchester Biomedical Research Centre. John Francis William Deakin has carried out paid consultancy work and speaking engagements for Servier, Merck Sharpe and Dohme, Astrazeneca, Janssen, Eli Lilly. The fees are paid to the University of Manchester to reimburse them for the time taken. The Manchester site received facility and staff support by the Wellcome Trust Clinical Research Facility. Lawrence Wilkinson declares consultancy work for the MRC (Non-clinical Fellowship Panel) and Welcome Trust (Neuroscience and Mental Health Funding Committee). John Francis William Deakin, Lawrence Wilkinson, Gerry Dawson, Colin Dourish and Kevin Craig own shares in P1vital Ltd. Lois Grayson’s salary as a postdoctoral research associate at Cardiff University was funded by P1vital Ltd. Ulrich Ettinger acknowledges funding by the Deutsche Forschungsgemeinschaft (ET 31/2-1) and a NIHR (National Institute for Health Research) Personal Award. Prof. Robin Morris and Prof. Steve Williams do not report any potential conflicts of interest. The views expressed in this publication are those of the authors and not necessarily those of the NHS, NIHR Department of Health or other funding bodies.

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Authors and Affiliations

  1. Department of Neuroimaging, Institute of Psychiatry, King’s College London, Centre for Neuroimaging Sciences, De Crespigny Park, P089, London, SE5 8AF, UK

    Anne Schmechtig, Lois Grayson, Katrina McMullen & Steve C. R. Williams

  2. Neuroscience and Psychiatry Unit, School of Community Based Medicine, The University of Manchester, Manchester, M13 9PT, UK

    Jane Lees, J. F. William Deakin & Ivan Koychev

  3. School of Psychology, Neuroscience and Mental Health Research Institute, Cardiff University, Tower Building. Park Place, Cardiff, CF10 3AT, UK

    Lois Grayson, Charlotte Perry & Lawrence Wilkinson

  4. P1vital Ltd, Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, OX3 7JX, UK

    Kevin J. Craig, Gerard R. Dawson & Colin T. Dourish

  5. Institute of Mental Health, Section of Forensic Mental Health, University of Nottingham, Sir Colin Campbell Building, Innovation Park, Triumph Road, Nottingham, NG7 2TU, UK

    Rukiya Dadhiwala

  6. Department of Psychological Medicine, Institute of Psychiatry, King’s College London, Westminster Bridge Road, London, SE1 7EH, UK

    Ellen M. Migo

  7. School of Medicine, Department of Psychological Medicine and Neurology, Neuroscience and Mental Health Research Institute, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Henry Wellcome Building, Heath Park, Cardiff, CF14 4XN, UK

    Lawrence Wilkinson

  8. Department of Psychology, Institute of Psychiatry, King’s College London, De Crespigny Park, London, SE5 8AF, UK

    Robin Morris

  9. Department of Psychology, University of Bonn, Kaiser-Karl-Ring 9, 53111, Bonn, Germany

    Ulrich Ettinger

Authors
  1. Anne Schmechtig
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  2. Jane Lees
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  3. Lois Grayson
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  4. Kevin J. Craig
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  7. J. F. William Deakin
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  8. Colin T. Dourish
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  9. Ivan Koychev
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  10. Katrina McMullen
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  11. Ellen M. Migo
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  12. Charlotte Perry
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  13. Lawrence Wilkinson
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  14. Robin Morris
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  15. Steve C. R. Williams
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  16. Ulrich Ettinger
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Corresponding author

Correspondence to Anne Schmechtig.

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Schmechtig, A., Lees, J., Grayson, L. et al. Effects of risperidone, amisulpride and nicotine on eye movement control and their modulation by schizotypy. Psychopharmacology 227, 331–345 (2013). https://doi.org/10.1007/s00213-013-2973-4

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  • DOI: https://doi.org/10.1007/s00213-013-2973-4

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