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Genetically Informative Mediation Modeling Applied to Stressors and Personality-Disorder Traits in Etiology of Alcohol Use Disorder

  • Tom Rosenström
  • Nikolai Olavi Czajkowski
  • Eivind Ystrom
  • Robert F. Krueger
  • Steven H. Aggen
  • Nathan A. Gillespie
  • Espen Eilertsen
  • Ted Reichborn-Kjennerud
  • Fartein Ask Torvik
Original Research

Abstract

A statistical mediation model was developed within a twin design to investigate the etiology of alcohol use disorder (AUD). Unlike conventional statistical mediation models, this biometric mediation model can detect unobserved confounding. Using a sample of 1410 pairs of Norwegian twins, we investigated specific hypotheses that DSM-IV personality-disorder (PD) traits mediate effects of childhood stressful life events (SLEs) on AUD, and that adulthood SLEs mediate effects of PDs on AUD. Models including borderline PD traits indicated unobserved confounding in phenotypic path coefficients, whereas models including antisocial and impulsive traits did not. More than half of the observed effects of childhood SLEs on adulthood AUD were mediated by adulthood antisocial and impulsive traits. Effects of PD traits on AUD 5‒10 years later were direct rather than mediated by adulthood SLEs. The results and the general approach contribute to triangulation of developmental origins for complex behavioral disorders.

Keywords

Statistical mediation model Twin study Causality Stressful life events Antisocial personality disorder Borderline personality disorder Substance use 

Notes

Acknowledgements

We acknowledge funding from the US National Institutes of Health and National Institute on Drug Abuse (1R01DA037558-01A1), the Research Council of Norway (226985 and 240061), the Norwegian Foundation for Health and Rehabilitation, the Norwegian Council for Mental Health, and the European Commission under the program “Quality of Life and Management of the Living Resources” of the Fifth Framework Program (QLG2-CT-2002-01254). TR had full access to all the data in this study and takes responsibility for the integrity of the data and the accuracy of the data analysis. The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Compliance with ethical standards

Conflict of interest

Tom Rosenström, Nikolai Czajkowski, Eivind Ystrom, Robert Krueger, Steven Aggen, Nathan Gillespie, Espen Eilertsen, Ted Reichborn-Kjennerud, and Fartein Torvik declare that they have no conflict of interest.

Ethical approval

Approval was received from The Norwegian Data Inspectorate and the Regional Committee for Medical and Health Research Ethics.

Human and animal rights

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

A written informed consent was obtained from all participants after a complete description of the study.

Supplementary material

10519_2018_9941_MOESM1_ESM.pdf (645 kb)
Supplementary material 1 (PDF 645 KB)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Tom Rosenström
    • 1
  • Nikolai Olavi Czajkowski
    • 1
    • 2
  • Eivind Ystrom
    • 1
    • 2
    • 3
  • Robert F. Krueger
    • 4
  • Steven H. Aggen
    • 5
  • Nathan A. Gillespie
    • 5
  • Espen Eilertsen
    • 1
  • Ted Reichborn-Kjennerud
    • 1
    • 6
  • Fartein Ask Torvik
    • 1
    • 2
  1. 1.Department of Mental DisordersNorwegian Institute of Public HealthOsloNorway
  2. 2.Department of PsychologyUniversity of OsloOsloNorway
  3. 3.PharmacoEpidemiology and Drug Safety Research Group, School of PharmacyUniversity of OsloOsloNorway
  4. 4.Department of PsychologyUniversity of MinnesotaMinneapolisUSA
  5. 5.Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral GeneticsVirginia Commonwealth UniversityRichmondUSA
  6. 6.Institute of Clinical MedicineUniversity of OsloOsloNorway

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