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Evidence for epistasis between the 5-HTTLPR and the dopamine D4 receptor polymorphisms in externalizing behavior among 15-year-olds

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Abstract

The present study aimed to clarify the functional role of genes in the dopamine and serotonin systems by examining whether polymorphisms in these genes are related to adolescent externalizing behavior either alone or in interaction with each other. Participants were selected from an ongoing prospective study of the outcome of early risk factors. At age 15 years, 298 adolescents (144 males, 154 females) completed the Youth Self Report, 296 primary caregivers the Child Behavior Checklist and 253 teachers the Teacher Report Form. DNA was genotyped for the DRD4 exon III VNTR and the 5-HTTLPR polymorphisms. Results revealed that individuals with the DRD4 7r allele reported significantly more externalizing behavior than carriers of other variants. In addition, a significant interaction emerged, indicating that adolescents carrying two copies of the 5-HTTLPR short allele and the DRD4 7r variant scored highest on aggressive and/or delinquent behavior compared to other genotypes. This result suggests an effect of 5-HTTLPR on externalizing behavior in the presence of DRD4 7r but no effect in its absence.

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Acknowledgments

This study was supported by grants from the German Research Foundation (DFG) and the Federal Ministry for Education and Research as part of the ‘Baden- Wuerttemberg Consortium for Addiction Research’ and the ‘National Genome Research Network’.

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Authors and Affiliations

  1. Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, J 5, 68159, Mannheim, Germany

    Sarah Hohmann, Katja Becker, Tobias Banaschewski, Martin H. Schmidt & Manfred Laucht

  2. Department of Child and Adolescent Psychiatry and Psychotherapy, Medical Faculty, Philipps-University of Marburg, Murburg, Germany

    Katja Becker

  3. Health Centre for the Deaf, Hospital St. John of God, Linz, Austria

    Johannes Fellinger

  4. Division of Clinical Psychology, Department of Psychology, University of Potsdam, Potsdam, Germany

    Günter Esser & Manfred Laucht

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  1. Sarah Hohmann
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  2. Katja Becker
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  3. Johannes Fellinger
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  4. Tobias Banaschewski
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  5. Martin H. Schmidt
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  6. Günter Esser
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  7. Manfred Laucht
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Correspondence to Manfred Laucht.

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Hohmann, S., Becker, K., Fellinger, J. et al. Evidence for epistasis between the 5-HTTLPR and the dopamine D4 receptor polymorphisms in externalizing behavior among 15-year-olds. J Neural Transm 116, 1621–1629 (2009). https://doi.org/10.1007/s00702-009-0290-1

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