Opioids and Maternal Brain-Behavior Adaptation During the Early Postpartum

项目摘要 R 01 DA 047336 -01：产后早期阿片类药物和母体脑行为适应 阿片类药物使用障碍（OUD）在美国是一种快速增长和毁灭性的流行病，影响了高 生育妇女的比例较高，许多人患有共病情绪障碍。未经治疗的阿片类药物使用和 依赖可能导致戒断症状，损害人际交往，并可能与 多物质使用和新生儿戒断综合征（NAS）。这些问题与更高的风险有关， 虐待儿童和昂贵的寄养服务。丁丙诺啡治疗（BT）减少戒断 以及非法阿片类药物对围产期妇女的其他有害影响。然而，BT对 母亲的神经生物学和婴儿为导向的行为的上下文中的OUD是未知的。临床前 母亲大脑行为研究和人类大脑磁共振成像（MRI）研究提供了 皮质边缘母视神经回路（MCN）模型对父母养育行为的影响。MCN包括 两个用于（1）母体护理的神经元抑制子系统，其由中间视前区介导， 下丘脑、腹侧被盖区、丘脑腹侧核和腹侧苍白球;（2）母性防御， 由导水管周围灰质介导。对于人类来说，MCN调节对他们的需求的灵活反应。 在产后早期，婴儿的哭声是独特的，在行为学上是显著的。我们 目的是研究一组接受BT治疗OUD的母亲（n=80）的人类MCN和母亲行为 与非OUD抑郁匹配对照组（MC，n=80）相比。所有受试者将接受2次MRI扫描：T1 产后1个月和产后4个月的T2。我们会测量母性的想法和行为- 包括以婴儿为导向的护理和防御措施，以及所有参与者的多种物质使用和情绪。 我们将使用多模式神经成像方法来测量静息状态下的功能连接，神经功能， 对自己婴儿哭声的反应，以及MCN的灰质体积。根据我们的初步研究， 临床前模型，我们假设，BT在OUD增加活动，在护理和防御 MCN的子系统，并减少这些子系统之间的正常相互抑制，导致 在潜在的解除抑制的母亲婴儿导向的防御性思想和行为。最后我们将 探索累积丁丙诺啡暴露（每日剂量x BT天数）对MCN生理学的影响， BT母亲组中的母亲行为，控制多物质使用和NAS。拟议 研究将阐明在OUD的背景下BT对父母养育的神经生物学的影响- 翻译潜力，以优化目前的方法来治疗母亲与OUD，并建议方向，以最好的 管理产后心理健康问题。

Project Summary R01 DA047336-01: Opioids and Maternal Brain-Behavior Adaptation During the Early Postpartum Opioid use disorder (OUD) is a fast-growing and devastating epidemic in the US, affecting a high proportion of child-bearing women, with many suffering comorbid mood disorders. Untreated opioid use and dependence may cause withdrawal symptoms, impair interpersonal interactions and may be associated with polysubstance use and neonatal abstinence syndrome (NAS). These problems are linked to higher risks of child maltreatment and costly utilization of foster care. Buprenorphine Treatment (BT) reduces withdrawal and other deleterious effects of illicit opioids for peripartum women. However, the effects of BT on maternal neurobiology and infant-oriented behaviors in the context of OUD are unknown. Preclinical maternal brain-behavior research and human brain magnetic resonance imaging (MRI) studies have provided a model of corticolimbic maternal caregiving neurocircuit (MCN) for parenting behaviors. The MCN includes two reciprocally inhibiting subsystems for (1) maternal care, mediated by the medial preoptic area in hypothalamus, ventral tegmental area, nucleus accumbens and ventral pallidum; and (2) maternal defense, mediated by periaqueductal grey. For humans, the MCN regulates flexible responses to the demands of their own infant – such as to the unique, ethologically salient own-baby cry – during the early postpartum period. We aim to examine the human MCN and maternal behaviors in a group of mothers undergoing BT for OUD (n=80) as compared to non-OUD depression Matched Controls (MC, n=80). All participant will have 2 MRI scans: T1 at 1-month postpartum and T2 at 4-month postpartum. We will measure maternal thoughts and behaviors – including measures of infant-oriented care and defense – and polysubstance use and moods in all participants. We will use multimodal neuroimaging methods to measure resting-state functional connectivity, neural responses to own-baby cry, and gray matter volumes of MCN. Based on our preliminary research and preclinical models we hypothesize that BT in OUD increases activity in both care and defense subsystems of MCN and diminishes normal reciprocal inhibition between these subsystems, resulting in potential disinhibition of maternal infant-oriented defensive thoughts and behaviors. Finally, we will explore the effects of cumulative buprenorphine exposure (daily dosage x days on BT) on MCN physiology and maternal behaviors within the group of BT mothers, controlling for polysubstance use and NAS. The proposed research will elucidate the effects of BT in the context of OUD on the neurobiology of parenting - with translational potential to optimize current approaches to treat mothers with OUD and suggest directions to best manage postpartum mental health issues.