Neuroimaging in Pregnancy to Assess Effects of Opioid Use Disorder

妊娠期神经影像学评估阿片类药物使用障碍的影响

• 批准号: 10665962
• 负责人: Rupa Radhakrishnan
• 金额: $ 23.78万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10665962
• 关键词: Adult; American; Anatomy; Body Weight; Brain; Buprenorphine; Child; Childhood; Clinical; Cognitive; Data; Diffusion Magnetic Resonance Imaging; Dose; Early identification; Effectiveness; Exposure to; Functional Magnetic Resonance Imaging; Future; Goals; Health; Human; Individual; Infant; Knowledge; Magnetic Resonance Imaging; Mental Depression; Metabolic Pathway; Metabolism; Methods; Mothers; Neonatal; Neonatal Abstinence Syndrome; Neurobiology; Opioid; Opioid replacement therapy; Outcome; Pharmaceutical Preparations; Physiological; Plasma; Postpartum Period; Pregnancy; Pregnancy Outcome; Pregnant Women; Prevention; Psyche structure; Public Health; Relapse; Research; Research Personnel; Rest; Risk; Severities; Structure; Third Pregnancy Trimester; Up-Regulation; Variant; Weight Gain; Withdrawal Symptom; Woman; adverse outcome; antenatal; behavioral outcome; buprenorphine treatment; craving; design; drug relapse; drug withdrawal; experience; fetal opioid exposure; gray matter; high risk; imaging biomarker; improved; individual variation; infant outcome; insight; maternal opioid use; maternal outcome; maternal risk; multimodal neuroimaging; neural circuit; neurodevelopment; neuroimaging; neuroimaging marker; neuromechanism; non-opioid analgesic; novel; opioid epidemic; opioid exposure; opioid use disorder; outcome prediction; pandemic disease; polysubstance use; predictive marker; pregnant; prenatal; prevent; prognostic; prognostic tool; relapse prediction; response; risk minimization; risk prediction; tool; treatment response; white matter

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.

项目摘要：美国孕妇中的阿片类药物使用障碍 (OUD) 是一个主要且不断增长的公众问题 尽管使用丁丙诺啡对 OUD 进行药物治疗，这些孕妇仍然存在健康问题。 处于早期复发、多物质使用和抑郁症的高风险中，从而使他们及其孩子的病情恶化 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磁共振成像 (rs-fMRI)。 产前阿片类药物暴露的婴儿的连通性与结果相关。 对患有 OUD 的孕妇进行神经影像学研究，以了解 OUD 的神经生物学效应， 妊娠妇女中丁丙诺啡的剂量反应和同时使用多种物质的影响。 服用丁丙诺啡 OUD 的女性，剂量递增和防止戒断的要求存在差异 由于体重增加和丁丙诺啡代谢上调而引起的症状和渴望 丁丙诺啡代谢的个体差异可能是治疗反应和治疗反应差异的基础。 我们的研究重点是个体不良的神经生物学结果，包括产后复发和抑郁症。 满足未满足的关键需求，以更好地了解大脑结构和功能的改变 妊娠与丁丙诺啡治疗剂量和血浆暴露相关，以优化母体 OUD 该应用的目的是表征 OUD 相关的产前母亲大脑结构和特征。 rs-fMRI 改变，以及丁丙诺啡治疗如何影响神经影像学上发现的这些改变。 我们项目的具体目标是评估母体大脑结构和 rs-fMRI 中 OUD 相关的改变 孕妇的连接性并评估母体大脑结构和 rs-fMRI 连接性的关联 该提案预计将提供 OUD 孕妇血浆丁丙诺啡的变化。 关于丁丙诺啡治疗对母亲大脑影响的重要新知识，以及对其影响的深入了解 怀孕期间个体丁丙诺啡代谢上调对这些大脑变化的影响最终。 结果将有助于开发孕产妇神经影像学作为早期识别孕产妇的潜在预后工具 和婴儿结局。