-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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA023134-05
Application #
8445338
Study Section
Special Emphasis Panel (ZRG1-HOP-T (04))
Program Officer
Boyce, Cheryl A
Project Start
2008-09-30
Project End
2014-03-31
Budget Start
2013-04-01
Budget End
2014-03-31
Support Year
5
Fiscal Year
2013
Total Cost
$185,169
Indirect Cost
$46,092
Name
Rhode Island Hospital
Department
Type
DUNS #
075710996
City
Providence
State
RI
Country
United States
Zip Code
02903
Marceau, Kristine; Palmer, Rohan H C; Neiderhiser, Jenae M et al. (2016) Passive rGE or Developmental Gene-Environment Cascade? An Investigation of the Role of Xenobiotic Metabolism Genes in the Association Between Smoke Exposure During Pregnancy and Child Birth Weight. Behav Genet 46:365-77
Marceau, Kristine; McMaster, Minni T B; Smith, Taylor F et al. (2016) The Prenatal Environment in Twin Studies: A Review on Chorionicity. Behav Genet 46:286-303
Knopik, Valerie S; Marceau, Kristine; Palmer, Rohan H C et al. (2016) Maternal Smoking During Pregnancy and Offspring Birth Weight: A Genetically-Informed Approach Comparing Multiple Raters. Behav Genet 46:353-64
Knopik, Valerie S; Marceau, Kristine; Bidwell, L Cinnamon et al. (2016) Smoking during pregnancy and ADHD risk: A genetically informed, multiple-rater approach. Am J Med Genet B Neuropsychiatr Genet 171:971-81
Bidwell, L C; Palmer, R H C; Brick, L et al. (2016) Genome-wide single nucleotide polymorphism heritability of nicotine dependence as a multidimensional phenotype. Psychol Med 46:2059-69
Bidwell, L Cinnamon; Knopik, Valerie S; Audrain-McGovern, Janet et al. (2015) Novelty Seeking as a Phenotypic Marker of Adolescent Substance Use. Subst Abuse 9:1-10
Palmer, Rohan H C; McGeary, John E; Heath, Andrew C et al. (2015) Shared additive genetic influences on DSM-IV criteria for alcohol dependence in subjects of European ancestry. Addiction 110:1922-31
Knopik, Valerie S; Heath, Andrew C; Marceau, Kristine et al. (2015) Missouri Mothers and Their Children: A Family Study of the Effects of Genetics and the Prenatal Environment. Twin Res Hum Genet 18:485-96
Bidwell, L C; McGeary, J E; Gray, J C et al. (2015) An initial investigation of associations between dopamine-linked genetic variation and smoking motives in African Americans. Pharmacol Biochem Behav 138:104-10
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

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