Neuroimaging in Pregnancy to Assess Effects of Opioid Use Disorder

项目概述：美国孕妇中的阿片类药物使用障碍(OUD)是一个主要的和不断增长的公众 健康问题。尽管使用丁丙诺啡进行药物治疗，这些孕妇仍在继续 早期复发、多药使用和抑郁症恶化的高危人群 结果。我们和其他研究人员之前已经展示了改变的大脑静息状态功能mri(rs-fmri)。 出生前有阿片类药物暴露的婴儿的连接性与预后相关。然而，没有 OUD孕妇的神经成像研究为了了解OUD的神经生物学效应， 丁丙诺啡在妊娠妇女中的剂量反应和同时使用多物质的影响。在怀孕期间 服用丁丙诺啡的女性在剂量递增和预防戒断的要求方面存在差异 体重增加和丁丙诺啡代谢可变上调引起的症状和渴求 小路。丁丙诺啡代谢的个体差异可能是治疗反应和 个体不良的神经生物学结果，包括产后复发和抑郁。我们的研究集中在 关于满足关键的未得到满足的需求，以更好地了解脑部结构和功能改变 与丁丙诺啡治疗剂量和血浆暴露相关的妊娠以优化母体分娩 结果。这项应用的目标是表征与胎儿期相关的母亲的大脑结构和 RS-fMRI改变，以及丁丙诺啡治疗如何影响神经成像确定的这些改变。 我们项目的具体目标是评估母体大脑结构和rs-fmri的相关变化。 孕妇的连通性，并评估孕妇脑结构和RS-fMRI连通性的相关性 妊娠合并尿毒症孕妇血浆丁丙诺啡的变化。这项提案预计将提供 关于丁丙诺啡治疗对母体大脑影响的重要新知识，以及对其影响的洞察 孕期个体丁丙诺啡代谢上调对这些脑部改变的影响。最终，这些 结果将有助于发展母体神经成像作为一种潜在的预后工具，用于早期识别母体 以及婴儿的结局。

Project Summary: Opioid use disorder (OUD) in pregnant American women is a major and growing public health concern. Despite medication treatment for OUD with buprenorphine, these pregnant women continue to be at high risk for early relapse, polysubstance use and depression worsening their and their children’s outcomes. We and other investigators have previously shown altered brain resting state functional MRI (rs-fMRI) connectivity in infants with prenatal opioid exposure that correlate with outcomes. However, there are no neuroimaging studies in pregnant women with OUD to understand the neurobiological effects of OUD, buprenorphine dose response and effects of concomitant polysubstance use in pregnant women. In pregnant women on buprenorphine OUD, there is variability in dose escalation and requirement to prevent withdrawal symptoms and craving due to increasing body weight and variable upregulation of buprenorphine metabolic pathways. Individual variability to buprenorphine metabolism may underlie variations in treatment response and individual poor neurobiological outcomes including postpartum relapse and depression. Our research is focused on fulfilling the critical unmet need to better understand the structural and functional brain alterations in pregnancy that correlate with buprenorphine treatment doses and plasma exposures to optimize maternal OUD outcomes. The objective of this application is to characterize OUD-related prenatal maternal brain structural and rs-fMRI alterations, and how buprenorphine treatment influences these alterations identified on neuroimaging. The specific aims of our project are to assess OUD related alterations in maternal brain structure and rs-fMRI connectivity in pregnant women and assess the associations of maternal brain structural and rs-fMRI connectivity alterations with plasma buprenorphine in pregnant women with OUD. This proposal is expected to provide critical new knowledge on the impact of buprenorphine treatment on maternal brain, and insight into the impact of individual buprenorphine metabolism upregulation in pregnancy on these brain alterations. Eventually, these results will help develop maternal neuroimaging as a potential prognostic tool for early identification of maternal and infant outcomes.