Prenatal cigarette exposure and genes: a pathway to sociopathy

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Molecular Psychiatry advance online publication 3 March 2009; doi: 10.1038/mp.2009.22

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

L S Wakschlag¹, E O Kistner², D S Pine³, G Biesecker¹, K E Pickett⁴, A D Skol⁵, V Dukic², R J R Blair³, B L Leventhal¹, N J Cox⁵, J L Burns¹, K E Kasza², R J Wright⁶ and E H Cook Jr¹

1. Institute for Juvenile Research, Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, USA
2. Department of Health Studies, University of Chicago, Chicago, IL, USA
3. Laboratory of Affective & Developmental Neurosciences, NIMH Intramural Research Program, Bethesda, MD, USA
4. Department of Health Sciences, University of York, York, England
5. Section of Genetic Medicine, Department of Medicine, University of Chicago, Chicago, IL, USA
6. Channing Laboratory, Harvard University Medical School, Boston, MA, USA

Correspondence: Dr LS Wakschlag, Institute for Juvenile Research, Department of Psychiatry, University of Illinois at Chicago, 1747 W. Roosevelt Road, MC747, Chicago, IL 60608, USA. E-mail: lwakschlag@psych.uic.edu

Received 2 October 2008; Revised 29 January 2009; Accepted 3 February 2009; Published online 3 March 2009.

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.