Based on widely replicated associations, it is now clear that prenatal exposure to tobacco exposure is either a risk marker for, or a causal contributor to, early onset disruptive behavior in offspring. However, the nature and mechanisms of exposure-related behavioral disruptions are poorly understood due to limitations of previous research. Moving beyond replication to testing alternative models and mechanisms requires a translational approach that (1) accurately measures exposure in close proximity to outcome;(2) integrates examination of exposure-related disruptive behavior and its neuropsychological substrates using direct assessment methods and;(3) examines exposure """"""""in context,"""""""" particularly elucidating the complex interplay of exposure, genetic susceptibility to disruptive behavior and, parenting behavior in these pathways. To this end, we propose a preschool follow-up of a pregnancy cohort oversampled for exposure to examine the following specific aims: (I) Establish the nature and independence of effects of exposure on disruptive behavior patterns and their neuropsychological substrates at preschool age using developmentally sensitive, direct assessments and, testing whether independent effects of exposure remains when passive gene- environment correlations (rGE) are modeled in tandem;(II) Examine whether responsive parenting modifies the relation of exposure, disruptive behavior patterns and their neuropsychological substrates, including testing the robustness of this interaction with rGE controlled;(III) Characterize how the association of exposure, disruptive behavior patterns and their neuropsychological substrates varies in children with differing dopaminergic and serotonergic genotypes, including testing for the robustness of these interactions when rGE is controlled. The study proposes an age 5 follow-up of the participants of the Midwest Infant Development Study (MIDS: DA014661, K. Espy, PI) (n=375). Exposure was assessed with repeated biologic and self-reported measures. Laboratory assessments of both disruptive behavior patterns and neuropsychological substrates, direct observations of maternal responsiveness and measured genotype will be utilized to assess the preschoolers. In this revised application, we will also collect questionnaire data on disruptive behavior patterns and responsive parenting for the siblings of the subjects (n=500) and measured genotype in the mothers and these siblings in order to conduct within-family analyses. This translational approach is designed to move beyond a scientific perspective that juxtaposes teratologic genetic and contextual processes as mutually exclusive alternative explanations to one that examines them in concert to explicate their relative contributions and mutual influence in pathways to emergent disruptive behavior. As a window on how prenatal insults to the brain and biologic and contextual risks interact in the early-onset of psychopathology, the study has substantial public health significance.

Public Health Relevance

While there is strong evidence that prenatal exposure to cigarettes is a risk marker for disruptive behavior, exposure related patterns and mechanisms are not well understood. Specifying exposure-related disruptive behavior patters and their neuropsychological substrates in young children and establishing mechanisms of effect, including the complex interplay of exposure, genetic susceptibility and parenting, will importantly advance understanding of the impact of this modifiable, prenatal risk factor on the emergence of the most common mental health problem of childhood.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Research Project (R01)
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Special Emphasis Panel (ZRG1-BBBP-N (02))
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Boyce, Cheryl A
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Northwestern University at Chicago
Public Health & Prev Medicine
Schools of Medicine
United States
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Massey, Suena H; Mroczek, Daniel K; Burns, James L et al. (2018) Positive parenting behaviors in women who spontaneously quit smoking during pregnancy: Clues to putative targets for preventive interventions. Neurotoxicol Teratol 67:18-24
Clark, Caron A C; Massey, Suena H; Wiebe, Sandra A et al. (2018) Does early maternal responsiveness buffer prenatal tobacco exposure effects on young children's behavioral disinhibition? Dev Psychopathol :1-14
Massey, Suena H; Hatcher, Amalia E; Clark, Caron A C et al. (2017) Does MAOA increase susceptibility to prenatal stress in young children? Neurotoxicol Teratol 61:82-91
Brown, D R; Bailey, J M; Oliveri, A N et al. (2016) Developmental exposure to a complex PAH mixture causes persistent behavioral effects in naive Fundulus heteroclitus (killifish) but not in a population of PAH-adapted killifish. Neurotoxicol Teratol 53:55-63
Estabrook, Ryne; Massey, Suena H; Clark, Caron A C et al. (2016) Separating Family-Level and Direct Exposure Effects of Smoking During Pregnancy on Offspring Externalizing Symptoms: Bridging the Behavior Genetic and Behavior Teratologic Divide. Behav Genet 46:389-402
Clark, C A C; Espy, K A; Wakschlag, L (2016) Developmental pathways from prenatal tobacco and stress exposure to behavioral disinhibition. Neurotoxicol Teratol 53:64-74
Wiebe, Sandra A; Clark, Caron A C; De Jong, Desiree M et al. (2015) Prenatal tobacco exposure and self-regulation in early childhood: Implications for developmental psychopathology. Dev Psychopathol 27:397-409
Nelson, Jennifer Mize; Choi, Hye-Jeong; Clark, Caron A C et al. (2015) Sociodemographic risk and early environmental factors that contribute to resilience in executive control: A factor mixture model of 3-year-olds. Child Neuropsychol 21:354-78
Massey, Suena H; Estabrook, Ryne; O'Brien, T Caitlin et al. (2015) Preliminary evidence for the interaction of the oxytocin receptor gene (oxtr) and face processing in differentiating prenatal smoking patterns. Neurosci Lett 584:259-64
Chevalier, Nicolas; James, Tiffany D; Wiebe, Sandra A et al. (2014) Contribution of reactive and proactive control to children's working memory performance: Insight from item recall durations in response sequence planning. Dev Psychol 50:1999-2008

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