Prenatal tobacco exposure: effects on neuropsychological outcomes and ADHD

产前烟草暴露：对神经心理学结果和多动症的影响

• 批准号: 8445338
• 负责人: Valerie S Knopik
• 金额: $ 18.52万
• 依托单位: RHODE ISLAND HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-30 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8445338
• 关键词: Accounting; Affect; Age; Alcohol or Other Drugs use; Attention; Attention deficit hyperactivity disorder; Basic Science; Behavior; Birth Records; Blood specimen; Brain region; Characteristics; Child; Childhood; Cognition; Cognitive; Cognitive deficits; Complement; Conduct Disorder; Confidential Information; DNA; Databases; Diagnostic; Enrollment; Environmental Tobacco Smoke; Event; Exposure to; Failure; Family; Fathers; Funding; Future; Genetic; Goals; Health; Health Personnel; Impaired cognition; Incentives; Infant; Interview; Language; Learning; Life; Literature; Low Birth Weight Infant; Masks; Measures; Memory; Missouri; Molecular Genetics; Mothers; Neurocognitive; Newborn Infant; Outcome; Parents; Perinatal; Pregnancy; Pregnant Women; Probability; Psychopathology; Public Health; Reading; Reporting; Research; Research Personnel; Risk; Risk Factors; Sampling; Scheme; School-Age Population; Shipping; Ships; Siblings; Smoke; Smoking; Symptoms; TNFRSF5 gene; Testing; Text; Time; Tobacco Dependence; Woman; Work; adolescent drug use; adolescent substance use; aged; base; clinically significant; cohort; design; early life exposure; executive function; externalizing behavior; fetal tobacco exposure; genetic analysis; interest; maternal cigarette smoking; neuropsychological; offspring; postnatal; prenatal; prenatal exposure; transmission process

ABSTRACT-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.

摘要-KNOPIK 这项重新修订的新研究者 R01 寻求资金来调查产前烟草暴露对 后代注意力问题以及相关的学习和认知缺陷。产妇怀孕期间吸烟 怀孕（MSDP）是一个主要的健康问题，与各种不良儿童结局的发生率较高有关， 包括注意力缺陷多动障碍（ADHD）、品行障碍、学习和记忆受损， 智商降低，认知功能障碍。 ADHD 和许多儿童期结局具有临床意义 具有明显公共卫生影响的条件，反过来也是青少年吸毒的重要预测因素 使用问题。然而，有证据表明 MSDP 对这些儿童结局有因果影响 由于经常无法区分这些产前烟草暴露，现有文献中的内容混乱不堪 其他混杂环境和遗传因素的影响。具体来说，之前的绝大多数 研究仅对产前暴露可能与父母的影响相关这一事实提供了有限的控制。 这些行为也可能成为重要的风险因素，进而传递给后代。未能 对此类（可能是遗传的）混杂因素的控制可能占建议的很大一部分 MSDP 与后代结果之间的关联，导致效应大小出现偏差。因此，这 应用程序建议从 400 名患者那里收集访谈和综合神经心理学实验室数据 至少有 2 个在密苏里州出生的孩子（测试时年龄为 8-15 岁）且母亲吸烟的家庭 在一次怀孕期间，但不是在同一个父亲的另一次怀孕期间（因此，后代吃饱了） 兄弟姐妹在产前烟草暴露方面不一致）。这种母亲内部和怀孕期间的对比 为混杂因素提供最佳的方法控制，例如遗传性和 预测 MSDP 可能性增加的母亲的社会人口学特征以及其他 怀孕期间吸烟和不吸烟的母亲（及其伴侣）之间的差异。这样的 混杂因素，如果不加以控制，可能会人为地创造或掩盖一个 MSDP 与儿童结果之间的关联（本提案特别感兴趣的是：记忆力、执行力 功能、语言/阅读和多动症）。因此，这样的设计将提供准确地 确定效应大小，同时也使我们能够开发一个队列，以便将来可以跟踪 纵向经历外化症状增加和物质使用开始的时期。

项目成果

NCAM1-TTC12-ANKK1-DRD2 variants and smoking motives as intermediate phenotypes for nicotine dependence.

• DOI: 10.1007/s00213-014-3748-2
• 发表时间: 2015-04
• 期刊: PSYCHOPHARMACOLOGY
• 影响因子: 3.4
• 作者: Bidwell, L. C.;McGeary, J. E.;Gray, J. C.;Palmer, R. H. C.;Knopik, V. S.;MacKillop, J.
• 通讯作者: MacKillop, J.

Grand challenge in behavioral and psychiatric genetics: quantitative challenges to keeping up with molecular advances.

行为和精神遗传学的巨大挑战：跟上分子进步的定量挑战。

• DOI: 10.3389/fgene.2011.00009
• 发表时间: 2011
• 期刊: Frontiers in genetics
• 影响因子: 3.7
• 作者: Knopik,ValerieS

Prenatal substance exposure and offspring development: Does DNA methylation play a role?

产前物质暴露和后代发育：DNA 甲基化是否发挥作用？

• DOI: 10.1016/j.ntt.2018.01.009
• 发表时间: 2019
• 期刊: Neurotoxicology and teratology
• 影响因子: 2.9
• 作者: Knopik,ValerieS;Marceau,Kristine;Bidwell,LCinnamon;Rolan,Emily
• 通讯作者: Rolan,Emily

Novelty Seeking as a Phenotypic Marker of Adolescent Substance Use.

• DOI: 10.4137/sart.s22440
• 发表时间: 2015
• 期刊: Substance abuse : research and treatment
• 作者: Bidwell LC;Knopik VS;Audrain-McGovern J;Glynn TR;Spillane NS;Ray LA;Riggs NR;Guillot CR;Pang RD;Leventhal AM
• 通讯作者: Leventhal AM

An initial investigation of associations between dopamine-linked genetic variation and smoking motives in African Americans.

• DOI: 10.1016/j.pbb.2015.09.018
• 发表时间: 2015-11
• 期刊: Pharmacology, biochemistry, and behavior
• 作者: Bidwell LC;McGeary JE;Gray JC;Palmer RH;Knopik VS;MacKillop J
• 通讯作者: MacKillop J