Opioids and Maternal Brain-Behavior Adaptation During the Early Postpartum

项目摘要 R01 DA047336-01：阿片类药物与产妇产后早期的脑行为适应 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，影响着一种 育龄妇女比例高，许多人同时患有情绪障碍。未经治疗的阿片类药物使用和 依赖可能导致戒断症状，损害人际互动，并可能与 多物质使用与新生儿禁欲综合征(NAS)。这些问题与更高的风险有关 虐待儿童和昂贵地利用寄养服务。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 母体神经生物学和以婴儿为导向的行为在母体发育不良的背景下是未知的。临床前 母亲的大脑行为研究和人脑磁共振成像(MRI)研究提供了 关于父母养育行为的皮质边缘母亲照顾神经回路模型。MCN包括 两个相互抑制的子系统：(1)由视前内侧区调节的母婴保健 下丘脑、腹侧被盖区、伏隔核和腹侧苍白球；(2)母性防御， 由中脑导水管周围的灰色调节。对于人类来说，MCN调节对其需求的灵活反应 自己的婴儿--比如对独特的、行为上突出的自己的婴儿--在产后早期哭。我们 目的检测80例接受Bt胎盘移植的母亲的母性行为和人类的母体行为。 与非抑郁对照组(MC，n=80)进行比较。所有参与者将进行2次MRI扫描：T1 产后1个月，产后4个月T2。我们将衡量母性的思想和行为- 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的功能连接，神经 对自己宝宝哭闹的反应，以及MCN的灰质体积。基于我们的初步研究和 临床前模型我们假设Bt在OUD增加护理和防御的活性 并消除这些子系统之间正常的相互抑制，从而导致 在潜在的去抑制母婴导向的防御思想和行为。最后，我们会 探讨丁丙诺啡累积暴露(每日剂量×Bt天数)对MCN生理和功能的影响 Bt母亲群体中的母亲行为，控制多种物质的使用和NAS。建议数 研究将阐明Bt在OUD背景下对父母养育的神经生物学的影响 优化当前治疗先天性巨结肠母亲的方法并提出最佳方向的翻译潜力 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.