Neuroimaging in Pregnancy to Assess Effects of Opioid Use Disorder

阿片类药物使用障碍（OUD）在美国孕妇是一个主要的和不断增长的公众 健康问题。尽管使用丁丙诺啡对OUD进行药物治疗，但这些孕妇继续 早期复发的风险很高，多种物质的使用和抑郁症恶化了他们和他们的孩子的 结果。我们和其他研究人员先前已经显示了改变的大脑静息状态功能磁共振成像（rs-fMRI） 产前阿片类药物暴露的婴儿的连接与结果相关。但没有 在患有OUD的孕妇中进行神经影像学研究以了解OUD的神经生物学效应， 丁丙诺啡的剂量反应和妊娠妇女合并使用多种药物的影响。妊娠 接受丁丙诺啡OUD的女性，剂量递增和预防停药的要求存在差异 由于体重增加和丁丙诺啡代谢的可变上调引起的症状和渴望 途径。丁丙诺啡代谢的个体差异可能是治疗反应和 个别不良的神经生物学结果，包括产后复发和抑郁症。我们的研究重点是 满足关键的未满足的需求，以更好地了解大脑的结构和功能变化， 妊娠与丁丙诺啡治疗剂量和血浆暴露相关，以优化母体OUD 结果。本申请的目的是表征OUD相关的产前母体脑结构和发育。 rs-fMRI改变，以及丁丙诺啡治疗如何影响神经影像学上确定的这些改变。 我们项目的具体目标是评估OUD相关的母体脑结构改变和rs-fMRI 连接，并评估母体大脑结构和rs-fMRI连接的关联 OUD孕妇血浆丁丙诺啡的变化。预计该提案将提供 关于丁丙诺啡治疗对孕产妇大脑影响的重要新知识，以及对影响的深入了解 个体丁丙诺啡代谢上调对这些大脑改变的影响。最终这些 结果将有助于发展母体神经影像学作为早期识别母体神经系统疾病的潜在预后工具。 婴儿的结果。

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.