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Role of Prenatal Exposure to Maternal Smoking and BDNF Genotype

Shahrdad Lotfipour, PhD; Eamonn Ferguson, PhD; Gabriel Leonard, PhD; Michel Perron, PhD; Bruce Pike, PhD; Louis Richer, PhD; Jean R. Séguin, PhD; Roberto Toro, PhD; Suzanne Veillette, PhD; Zdenka Pausova, MD; Tomá Paus, MD, PhD

Arch Gen Psychiatry. 2009;66(11):1244-1252.

Context  Prenatal exposure to maternal cigarette smoking (PEMCS) may affect brain development and behavior in adolescent offspring.

Objective  To evaluate the involvement of the orbitofrontal cortex (OFC) in mediating the relationship between PEMCS and substance use.

Design  Cross-sectional analyses from the Saguenay Youth Study aimed at evaluating the effects of PEMCS on brain development and behavior among adolescents. Nonexposed adolescents were matched with adolescents exposed prenatally to cigarette smoking by maternal educational level.

Participants and Setting  A French Canadian founder population of the Saguenay–Lac-Saint-Jean region of Quebec, Canada.

The behavioral data set included 597 adolescents (275 sibships; 12-18 years of age), half of whom were exposed in utero to maternal cigarette smoking. Analysis of cortical thickness and genotyping were performed using available data from 314 adolescents.

Main Outcome Measures  The likelihood of substance use was assessed with the Diagnostic Interview Schedule for Children Predictive Scales. The number of different drugs tried by each adolescent was assessed using another questionnaire. Thickness of the OFC was estimated from T1-weighted magnetic resonance images using FreeSurfer software.

Results  Prenatal exposure to maternal cigarette smoking is associated with an increased likelihood of substance use. Among exposed adolescents, the likelihood of drug experimentation correlates with the degree of OFC thinning. In nonexposed adolescents, the thickness of the OFC increases as a function of the number of drugs tried. The latter effect is moderated by a brain-derived neurotrophic factor (BDNF) genotype (Val66Met).

Conclusions  We speculate that PEMCS interferes with the development of the OFC and, in turn, increases the likelihood of drug use among adolescents. In contrast, we suggest that, among nonexposed adolescents, drug experimentation influences the OFC thickness via processes akin to experience-induced plasticity.

Author Affiliations: Brain and Body Centre (Drs Lotfipour, Toro, Pausova, and Paus) and School of Psychology (Dr Ferguson), University of Nottingham, United Kingdom; Montréal Neurological Institute, McGill University (Drs Leonard, Pike, and Paus), and Hospital Centre of the University of Montreal (Drs Perron, Veillette, and Pausova), and Department of Psychiatry (Dr Séguin) and University of Montreal, Montreal, Quebec, Canada; Department of Psychology, University of Quebec in Chicoutimi, Chicoutimi, Quebec (Dr Richer); and Cégep de Jonquière, Jonquiere, Quebec (Drs Perron and Veillette).

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