Ecological Momentary Assessment of Posttraumatic Stress Disorder and Prenatal Bonding Predicting Opioid Use Disorder Relapse Among Pregnant Women

这项重新提交的申请响应了PA-18-602，并试图在日常基础上确定怀孕期间创伤后应激障碍（PTSD）症状与阿片类药物使用障碍（OUD）复发的关系，这是研究中的一个根本空白。建立了一个理论框架，确定产前结合和阿片类药物渴望是中介，情绪调节和焦虑敏感性是中心PTSD/复发关系的调节因子。这将是第一个调查孕妇OUD复发的风险和保护因素的时间起伏的研究，因此，这项研究推进了更常见的研究情况，使用固定评估来调查患有各种物质使用障碍（SUD）的孕妇。这是一个很好的模型，因为孕妇有独特的特征，随着时间的推移而改变，可能与复发有关。他们患PTSD（复发风险因素和常见的OUD合并症）的比例很高，而PTSD的线索会诱发渴望，从而引发复发。重要的是，孕妇有一个独特的相关生物学变量，可能是一个保护因素-产前胎儿结合。本研究的长期目标是开发基于经验的移动健康干预措施，以针对实时发生的OUD复发的近端风险。中心假设是，在怀孕期间，PTSD症状会随着时间的推移而波动，并会增加或减少近端复发风险，PTSD/复发关系将由阿片类药物渴望和产前结合的波动介导，并由特质情绪调节和焦虑敏感性调节。基本原理是与复发相关的因素不是静态的，而是随时间波动的。此外，复发事件发生在时间的某个时刻。我们建议使用生态瞬时评估（EMA：使用移动设备）收集波动风险因素和阿片类药物使用的数据，每天多次使用混合事件和基于时间的设计，持续6周，以评估孕妇OUD复发的近端风险因素（N=75）。妊娠期OUD复发不同于其他SUD，因为药物辅助治疗是推荐的护理标准，因此最好单独检查。在强有力的初步数据支持设计可行性的指导下，这一假设将通过两个具体目标进行检验：目标1。检查怀孕期间PTSD症状与阿片类药物使用之间的近实时关联。目标2。检查怀孕期间PTSD症状与阿片类药物使用之间的关联的中介（产前结合和渴望）和调节因子（焦虑敏感性和情绪调节）。这项研究具有重要意义，因为它有望促进我们对PTSD症状、渴望和妊娠特异性保护因素（产前结合）的波动如何影响OUD复发的理解。最终，这些知识将导致为孕妇量身定制的基于科学的移动健康应用程序。该方法具有创新性，因为它针对的是未充分研究的人群，并检查OUD复发的近端风险和保护因素的波动，同时使用一种以前未在此背景下应用的技术（EMA）来考虑调节因素。

This resubmitted application responds to PA-18-602 and seeks to determine on a day-to-day basis how, during pregnancy, posttraumatic stress disorder (PTSD) symptoms are associated with opioid use disorder (OUD) relapse, a fundamental gap in the research. A theoretical framework is developed that identifies prenatal bonding and opioid craving as mediators, and emotion regulation and anxiety sensitivity as moderators, of the central PTSD/relapse relationship. This will be the first study to investigate the temporal ebb and flow of risk and protective factors for OUD relapse for pregnant women and, as such, this study advances the more common situation where research, using fixed assessments, investigates pregnant women with various substance use disorders (SUD). This is an excellent model because pregnant women have unique characteristics that change over time potentially associated with relapse. They have high rates of PTSD (relapse risk factor and common OUD comorbidity), and PTSD cues induce craving that triggers relapses. Importantly, pregnant women have a unique relevant biological variable that may be a protective factor - prenatal fetal bonding. The long term goal of this research is to develop empirically-based mobile-health interventions to target proximal risks for OUD relapse as they occur in real time. The central hypothesis is that during pregnancy PTSD symptoms will fluctuate over time and will increase or reduce proximal risk of relapse, and that the PTSD/relapse relationship will be mediated by fluctuations in opioid craving and prenatal bonding and moderated by trait emotion regulation and anxiety sensitivity. The rationale is that factors associated with relapse are not static, but fluctuate over time. Moreover, relapse events occur at moments in time. We propose to use ecological momentary assessment (EMA: using mobile devices) to collect data on fluctuating risk factors and opioid use multiple times per day using a mixed event and time-based design for 6 weeks, to assess proximal risk factors for OUD relapse in pregnant women (N=75). OUD relapse during pregnancy differs from other SUD, since medication-assisted treatment is the recommended standard of care, and is thus better examined separately. Guided by strong preliminary data supporting design feasibility, this hypothesis will be tested via two specific aims: Aim 1. Examine near real time associations during pregnancy between PTSD symptoms and opioid use. Aim 2. Examine mediators (prenatal bonding and craving) and moderators (anxiety sensitivity and emotion regulation) of associations during pregnancy between PTSD symptoms and opioid use. The proposed research is significant, because it is expected to advance our understanding of how fluctuations in PTSD symptoms, craving, and a pregnancy specific protective factor – prenatal bonding – impact OUD relapse. Ultimately, this knowledge will lead to science-based mobile-health applications tailored for pregnant women. The approach is innovative because it targets an understudied population and examines fluctuation in proximal risk and protective factors for OUD relapse, while accounting for moderators, using a technique (EMA) not previously applied in this context.