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Interaction of prenatal exposure to cigarettes and MAOA genotype in pathways to youth antisocial behavior

Molecular Psychiatry volume 15, pages 928–937 (2010)Cite this article

Abstract

Genetic susceptibility to antisocial behavior may increase fetal sensitivity to prenatal exposure to cigarette smoke. Testing putative gene × exposure mechanisms requires precise measurement of exposure and outcomes. We tested whether a functional polymorphism in the gene encoding the enzyme monoamine oxidase A (MAOA) interacts with exposure to predict pathways to adolescent antisocial behavior. We assessed both clinical and information-processing outcomes. One hundred seventy-six adolescents and their mothers participated in a follow-up of a pregnancy cohort with well-characterized exposure. A sex-specific pattern of gene × exposure interaction was detected. Exposed boys with the low-activity MAOA 5′ uVNTR (untranslated region variable number of tandem repeats) genotype were at increased risk for conduct disorder (CD) symptoms. In contrast, exposed girls with the high-activity MAOA uVNTR genotype were at increased risk for both CD symptoms and hostile attribution bias on a face-processing task. There was no evidence of a gene–environment correlation (rGE). Findings suggest that the MAOA uVNTR genotype, prenatal exposure to cigarettes and sex interact to predict antisocial behavior and related information-processing patterns. Future research to replicate and extend these findings should focus on elucidating how gene × exposure interactions may shape behavior through associated changes in brain function.

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Acknowledgements

This work was supported by NIDA Grant DA15223 to Dr Wakschlag, including support to Drs Pickett, Cook, Dukic, Wright and Leventhal. Drs Wakschlag, Leventhal and Cook were also supported by the Walden & Jean Young Shaw and Children's Brain Research Foundations, and Dr Pickett was supported by a UK National Institute for Health Research Career Scientist Award. Very special thanks to our colleagues, Margaret Briggs-Gowan, Kimberly Espy, David Henry, Brian Mustanski and Patrick Tolan, whose ongoing critical feedback and consultation on this work has been invaluable. We thank Ira Tager, the founder of MISSEB, for his enthusiasm about the EBFS follow-up and for facilitating access to this cohort. We gratefully acknowledge Neal Benowitz's contribution to exposure measurement. Vincent Smeriglio's steadfast commitment to this program of research is deeply appreciated. We thank Nora Volkow for guidance on the scientific approach taken in this study. Finally, we thank the EBFS research staff, whose thoughtful efforts were vital to study completion, particularly Marian Parker's work on re-ascertainment, Phil Schumm and Ted Pollari's work on electronic data transmission, and Kathy Hennessy and Greg Moy of the IJR Laboratory of Developmental Neuroscience for their work on genotyping. Portions of this paper were presented at the Meetings of the American College of Neuropsychopharmacology, the Society for the Study of Addiction and the Society for Research in Child Development.

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Authors and Affiliations

  1. Department of Psychiatry, Institute for Juvenile Research, University of Illinois at Chicago, Chicago, IL, USA

    L S Wakschlag, G Biesecker, B L Leventhal, J L Burns & E H Cook Jr

  2. Department of Health Studies, University of Chicago, Chicago, IL, USA

    E O Kistner, V Dukic & K E Kasza

  3. Laboratory of Affective & Developmental Neurosciences, NIMH Intramural Research Program, Bethesda, MD, USA

    D S Pine & R J R Blair

  4. Department of Health Sciences, University of York, York, England

    K E Pickett

  5. Department of Medicine, Section of Genetic Medicine, University of Chicago, Chicago, IL, USA

    A D Skol & N J Cox

  6. Channing Laboratory, Harvard University Medical School, Boston, MA, USA

    R J Wright

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  1. L S Wakschlag
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  2. E O Kistner
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Correspondence to L S Wakschlag.

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Wakschlag, L., Kistner, E., Pine, D. et al. Interaction of prenatal exposure to cigarettes and MAOA genotype in pathways to youth antisocial behavior. Mol Psychiatry 15, 928–937 (2010). https://doi.org/10.1038/mp.2009.22

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