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NEUROTICISM MEDIATES THE EFFECT OF P2RX7 ON OUTCOMES OF MOOD DISORDERS

Authors

  • Outi Mantere M.D., Ph.D.,

    Corresponding author
    1. Department of Psychiatry, Jorvi Hospital, Helsinki University Central Hospital, Espoo, Finland
    2. MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, United Kingdom
    • Department of Mental Health and Substance Use, National Institute for Health and Welfare, Helsinki, Finland
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  • Pia Soronen M.Sc.,

    1. Genomics Unit and Institute for Molecular Medicine FIMM, National Institute for Health and Welfare, Helsinki, Finland
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  • Rudolf Uher M.U., Dr., Ph.D.,

    1. MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, United Kingdom
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  • Mikko Ketokivi M.D., M.Sc.,

    1. Operations and Technology Department, IE Business School, Madrid, Spain
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  • Pekka Jylhä M.D., Ph.D.,

    1. Department of Mental Health and Substance Use, National Institute for Health and Welfare, Helsinki, Finland
    2. Department of Psychiatry, Jorvi Hospital, Helsinki University Central Hospital, Espoo, Finland
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  • Tarja Melartin M.D., Ph.D.,

    1. Department of Mental Health and Substance Use, National Institute for Health and Welfare, Helsinki, Finland
    2. Department of Psychiatry, Jorvi Hospital, Helsinki University Central Hospital, Espoo, Finland
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  • Tiina Paunio M.D., Ph.D.,

    1. Department of Mental Health and Substance Use, National Institute for Health and Welfare, Helsinki, Finland
    2. Genomics Unit and Institute for Molecular Medicine FIMM, National Institute for Health and Welfare, Helsinki, Finland
    3. Department of Psychiatry, Helsinki University Central Hospital, Helsinki, Finland
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  • Erkki Isometsä M.D., Ph.D.

    1. Department of Mental Health and Substance Use, National Institute for Health and Welfare, Helsinki, Finland
    2. Department of Psychiatry, Helsinki University Central Hospital, Helsinki, Finland
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  • Conflict of interest: None of the authors declares competing interests.

Correspondence to: Outi Mantere, Senior Researcher, Department of Mental Health and Substance Abuse Services, National Institute of Health and Welfare, P.O. Box 30, 00271 Helsinki, Finland. Fax: +358-9-471-63735. E-mail: outi.mantere@thl.fi

Abstract

Background

We previously reported an association between P2RX7 variant rs208294, diagnosis, and the longitudinal course of mood disorders. Here, we test whether the personality trait neuroticism mediates the effect of P2RX7 on the course of mood disorders.

Methods

Patients with DSM-IV mood disorder (256 with major depressive disorder and 168 with bipolar disorder [BD]) were diagnosed with semistructured interviews, genotyped, and followed up for a median of 60 (range 6–83) months. The primary outcome was the prospectively assessed proportion of time spent in any DSM-IV mood episode (time ill). Three types of genetic effect were tested in structural equations models: Model 1: genes directly affect outcome independent of neuroticism, Model 2: neuroticism mediates the effect of genes on outcome, and Model 3: neuroticism and the genetic variant interact in their effect on outcome.

Results

Neuroticism mediated the P2RX7 genetic effect on outcome. The T allele of rs208294 was associated with higher neuroticism, which in turn predicted a higher proportion of time spent in mood episodes (the bootstrap-based test of indirect effect, P = .02). There was no significant interaction between neuroticism and the genotype.

Conclusion

Neuroticism is likely to lie on the causal pathway between the rs208294 T variant and the adverse long-term course of major depressive and BDs. Depression and Anxiety 00:1-8, 2012. © 2012 Wiley Periodicals, Inc.

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