Prenatal Neuroendocrine Mediators of Young Adult Smoking

描述（由申请人提供）：母亲在怀孕期间吸烟（MSDP）与后代吸烟风险显著增加有关。鉴于吸烟的高社会成本，以及后代吸烟的跨代传播风险，阐明MSDP-后代吸烟联系的潜在机制对于干预和预防工作至关重要。承认混淆因素（例如，遗传影响，母体精神共病）也可能是MSDP-后代吸烟联系的基础，我们跟踪Kandel和Udry先前显示的影响吸烟母亲后代吸烟吸收的一种潜在机制。在唯一一项研究MSDP-后代吸烟联系的潜在机制的研究中，Kandel和Udry发现怀孕期间母体睾酮水平的增加与女性后代吸烟风险的增加有关。在拟议的研究中，我们有一个前所未有的机会来扩大坎德尔和Udry的研究结果，通过检查两个母体激素（睾酮和皮质醇）在怀孕期间作为中介的MSDP和后代尼古丁依赖症状之间的联系，在男性和女性使用后代从国家围产期合作项目（NCPP）的普罗维登斯队列。NCPP的普罗维登斯队列的693只成年后代将纳入本研究。母亲吸烟以前作为原始国家清洁生产计划组合的一部分进行了前瞻性评估。还通过对原始NCPP队列的随访研究评估了后代的尼古丁依赖症状。通过与NIH工作人员的合作，可以获得妊娠三个月的母体血清。对这项提案的资助将使我们能够分析产妇血清中的睾酮（及其结合蛋白）和皮质醇（及其结合蛋白）以及可替宁（尼古丁代谢物）。然后，将利用一系列回归分析来检验我们的假设，即母体游离睾酮和游离皮质醇水平是男性和女性中MSDP与尼古丁依赖后代症状（通过自我报告和母体可替宁水平测量）之间联系的介质。确定MSDP-后代吸烟联系的潜在机制可能会导致针对怀孕吸烟者和高危后代的干预和预防工作。此外，阐明MSDP后代吸烟联系的潜在机制也将是防止MSDP传播的第一步。

DESCRIPTION (provided by applicant): Maternal smoking during pregnancy (MSDP) has been linked to significantly increased risk for offspring smoking uptake. Given high societal costs of smoking, and risk for transgenerational transmission of offspring smoking, elucidating mechanisms underlying the MSDP-offspring smoking link is critical for intervention and prevention efforts. Acknowledging the possibility that confounding factors (e.g., genetic influences, maternal psychiatric comorbidities) may also underlie the MSDP-offspring smoking link, we follow up on one potential mechanism shown previously by Kandel and Udry l to influence smoking uptake in offspring of smoking mothers. In the only study to examine mechanisms underlying the MSDP-offspring smoking link, Kandel and Udry found that increased maternal testosterone levels during pregnancy were associated with increased risk for smoking uptake in female offspring. In the proposed study, we have an unprecedented opportunity to expand on Kandel and Udry's findings by examining two maternal hormones (testosterone and cortisol) during pregnancy as mediators of links between MSDP and offspring symptoms of nicotine dependence in both males and females using offspring from the Providence Cohort of the National Collaborative Perinatal Project (NCPP). Six hundred ninety-three adult offspring from the Providence cohort of the NCPP will be included in the study. Maternal smoking was previously assessed prospectively as part of the original NCPP battery. Symptoms of nicotine dependence in offspring were also assessed through a follow-up study of the original NCPP cohort. Maternal sera from three trimesters of pregnancy are accessible through collaboration with NIH personnel. Funding for this proposal will allow us to assay maternal sera for testosterone (and its binding protein) and cortisol (and its binding protein) as well as cotinine (a nicotine metabolite). A series of regression analyses will then be utilized to test our hypotheses regarding maternal levels of free testosterone and free cortisol as mediators of links between MSDP and offspring symptoms of nicotine dependence (measured by self-report and maternal cotinine levels) in both males and females. Identification of mechanisms underlying the MSDP-offspring smoking link may lead to targeted intervention and prevention efforts in pregnant smokers and high-risk offspring. Further, elucidating mechanisms underlying the MSDPoffspring smoking link will also represent a first step toward preventing the transmission of MSDP.