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：孕妇妇女中的阿片类药物使用障碍（OUD）是一个主要的公众 健康问题。尽管用丁丙诺啡治疗OUD，这些孕妇仍在 早期救济，多物质使用和抑郁症的风险很高，使他们及其子女担心 结果。我们和其他研究人员先前已经显示出改变大脑静止状态功能MRI（RS-FMRI） 与预后相关的产前阿片类药物暴露的婴儿的连通性。但是，没有 对患有OUD孕妇的神经影像学研究，以了解Oud的神经生物学作用， 丁丙诺啡剂量的反应和孕妇伴随多义能使用的影响。在怀孕 丁丙诺啡的女性，剂量升级和要求升级的要求有所不同 肌吗啡代谢的体重增加和可变上调引起的症状和渴望 途径。丁丙诺啡代谢的个人变异性可能是治疗反应和 个体的贫困神经生物学结果，包括产后缓解和抑郁症。我们的研究集中 满足关键的未满足需要，以更好地了解结构性和功能性大脑的改变 与丁丙诺啡治疗剂量和血浆暴露相关的怀孕以优化遗产 结果。该应用的目的是表征与Oud相关的产前大脑结构和 RS-FMRI改变，以及丁丙诺啡治疗如何影响这些在神经影像学上确定的改变。 我们项目的具体目的是评估材料大脑结构和RS-FMRI的OUD相关变化 孕妇的连通性和评估母体大脑结构和RS-FMRI连通性的关联 OUD孕妇血浆丁丙诺啡的改变。预计该建议将提供 关于丁丙诺啡治疗对母校的影响的重要新知识，并深入了解影响 在这些大脑改变的怀孕中，单个丁丙诺啡代谢上调。最终，这些 结果将有助于发展母体神经影像作为早期鉴定母体的潜在预后工具 和婴儿的结果。