-KNOPIK This re-revised new investigator R01 seeks funding to investigate the effects of prenatal tobacco exposure on offspring attention problems and associated learning and cognitive deficits. Maternal smoking during pregnancy (MSDP) is a major health concern associated with higher rates of a variety of poor child outcomes, including attention deficit hyperactivity disorder (ADHD), conduct disorder, impaired learning and memory, lowered IQ, and cognitive dysfunction. ADHD and many of these childhood outcomes are clinically significant conditions with clear public health implications and also are, in turn, substantial predictors of adolescent drug use problems. However, the evidence suggesting causal effects of MSDP for these childhood outcomes is muddied in the existing literature due to the frequent inability to separate these prenatal tobacco exposure effects from other confounding environmental and genetic factors. Specifically, the vast majority of prior studies provide only limited control for the fact that prenatal exposures may be correlated with parental behaviors that could also act as important risk factors that are in turn transmitted to their offspring. Failure to control for such (possibly heritable) confounding factors may account for a large part of the suggested associations between MSDP and offspring outcomes, resulting in biased effect sizes. Therefore, this application proposes to collect interview and comprehensive neuropsychological lab-based data from 400 families with at least 2 Missouri-born children (aged 8-15 at the time of testing), where the mother smoked during one pregnancy but not during a another pregnancy by the same father (thus, with offspring who are full sibling pairs discordant for prenatal tobacco exposure). This within-mother, between-pregnancy contrast provides the best possible methodologic control for confounding factors, such as heritable and sociodemographic characteristics of the mother that predict increased probability of MSDP, as well as other differences between mothers who do and do not smoke during pregnancy (and their partners). Such confounding factors, if not controlled for, might otherwise artifactually create, or alternatively mask, an association between MSDP and child outcomes (of particular interest for this proposal: memory, executive function, language/reading, and ADHD). Such a design will therefore provide opportunities to accurately determine effect sizes while also allowing us to develop a cohort which, in the future, could be followed longitudinally through periods of increased externalizing symptoms and substance use initiation.

Public Health Relevance

In two or three sentences, describe the relevance of this research to public health. If the application is funded, this description, as is, will become public information. Therefore, do not include proprietary/confidential information. Maternal smoking during pregnancy (MSDP) is a major public health concern with nearly half of all women who smoke continuing to do so throughout their pregnancies. As a result, more than half a million infants per year are prenatally exposed to maternal smoking. This genetically informed study on effects of prenatal exposure considers the potential confounding effects of differences between women who smoke and don't smoke during pregnancy. Findings could provide yet one more incentive for pregnant women to overcome tobacco dependence and quit, but findings can also guide treatment providers to think more comprehensively about smoking during pregnancy and the potential correlates of said behavior.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Research Project (R01)
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Special Emphasis Panel (ZRG1-HOP-T (04))
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Boyce, Cheryl A
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Rhode Island Hospital
United States
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Palmer, Rohan H C; Brick, Leslie; Nugent, Nicole R et al. (2015) Examining the role of common genetic variants on alcohol, tobacco, cannabis and illicit drug dependence: genetics of vulnerability to drug dependence. Addiction 110:530-7
Bidwell, L C; McGeary, J E; Gray, J C et al. (2015) NCAM1-TTC12-ANKK1-DRD2 variants and smoking motives as intermediate phenotypes for nicotine dependence. Psychopharmacology (Berl) 232:1177-86
Stuart, Gregory L; McGeary, John E; Shorey, Ryan C et al. (2014) Genetic associations with intimate partner violence in a sample of hazardous drinking men in batterer intervention programs. Violence Against Women 20:385-400
Xu, Xiaomeng; Clark, Uraina S; David, Sean P et al. (2014) Effects of nicotine deprivation and replacement on BOLD-fMRI response to smoking cues as a function of DRD4 VNTR genotype. Nicotine Tob Res 16:939-47
Palmer, Rohan H C; Knopik, Valerie S; Rhee, Soo Hyun et al. (2013) Prospective effects of adolescent indicators of behavioral disinhibition on DSM-IV alcohol, tobacco, and illicit drug dependence in young adulthood. Addict Behav 38:2415-21
Bidwell, L Cinnamon; Metrik, Jane; McGeary, John et al. (2013) Impulsivity, variation in the cannabinoid receptor (CNR1) and fatty acid amide hydrolase (FAAH) genes, and marijuana-related problems. J Stud Alcohol Drugs 74:867-78
Flessner, Christopher A; Knopik, Valerie S; McGeary, John (2012) Hair pulling disorder (trichotillomania): genes, neurobiology, and a model for understanding impulsivity and compulsivity. Psychiatry Res 199:151-8
Josephs, Robert A; Telch, Michael J; Hixon, J Gregory et al. (2012) Genetic and hormonal sensitivity to threat: testing a serotonin transporter genotype × testosterone interaction. Psychoneuroendocrinology 37:752-61
Flessner, Christopher A (2011) Cognitive-behavioral therapy for childhood repetitive behavior disorders: tic disorders and trichotillomania. Child Adolesc Psychiatr Clin N Am 20:319-28
Knopik, Valerie S (2010) Commentary: smoking during pregnancy--genes and environment weigh in. Int J Epidemiol 39:1203-5