Opioids and Maternal Brain-Behavior Adaptation During the Early Postpartum

项目摘要 阿片类药物与产妇产后早期脑行为适应 阿片类药物使用障碍在美国是一种快速增长和毁灭性的流行病，影响到很高比例的 生育妇女，许多人患有共同的情绪障碍。未经治疗的阿片类药物使用和依赖 可能会导致戒断症状，损害人际交往，并可能与多种物质有关 使用和新生儿禁欲综合征。这些问题与虐待儿童的风险更高有关， 寄养服务的使用成本高昂。丁丙诺啡治疗(BT)减少戒断和其他有害因素 非法阿片类药物对孕妇的影响。然而，Bt对母体神经生物学和 以婴儿为导向的行为是未知的。临床前母体脑行为研究与人脑 磁共振成像(Mri)研究提供了一种皮质边缘母亲照料的模型。 神经回路(MCN)对父母养育和后代存活的影响。该MCN包括两个相互调制 (1)由腹侧下丘脑内侧视前区(MPOA)调节的产妇照料系统 被盖区(VTA)、伏隔核(NAC)和腹侧苍白球；(2)母亲的防御/攻击性 行为，由导水管周围灰质(PAG)介导。对于人类来说，MCN调节对 要求自己的婴儿在产后早期适应--如对独特的， 行为上突出的自己的宝宝哭声。我们的目标是研究人类MCN和一组母性行为 接受BT治疗的阿片依赖母亲(n=80)，与使用抑郁症的非阿片依赖母亲进行比较 对照组(MC，n=80)。所有参与者都将接受两次MRI扫描：产后1个月进行T1扫描，4个月进行T2扫描 产后。所有参与者的药物使用和情绪将在这两个时间点进行评估。我们会 结合多模式神经成像方法，包括对自己的婴儿哭声、灰质的功能反应 数量和休息状态活动以及对母亲照料思想和行为的评估--包括 敏感和敌意的测量-在T1和T2。基于我们的初步研究和临床前模型 我们假设BT增加了照顾自己的MCN对他人的反应--婴儿哭闹等 影响与母亲的照料思想和行为有关。我们预测T1到T2塑料 MCN的适应性将受到Bt的影响，因此Bt可能会干扰正常对立的照看 和MCN的防御子系统。我们的控制将包括招募抑郁症匹配的参与者 母婴厌恶感、多物质使用和子代新生儿禁欲的统计控制 综合症。最后，我们将探索这些因素对群体内大脑和母性行为的影响 接受过Bt治疗的母亲。这项拟议的研究将阐明Bt对育儿的神经生物学的影响 -具有优化当前方法的翻译潜力，并提出最好地管理产后的方向 心理健康问题，改善母子关系和儿童结局--一种基于大脑的生物标记物。

Project Summary Opioids and Maternal Brain-Behavior Adaptation During the Early Postpartum Opioid use disorder 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. 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 expectant mothers. However, the effects of BT on maternal neurobiology and infant-oriented behaviors are unknown. Preclinical maternal brain-behavior research and human brain magnetic resonance imaging (MRI) studies have provided a model of corticolimbic maternal caregiving neurocircuits (MCN) for parenting and offspring survival. The MCN includes two reciprocally modulating systems for (1) maternal caregiving, mediated by the hypothalamic medial preoptic area (mPOA), ventral tegmental area (VTA), nucleus accumbens (NAc) and ventral pallidum; and (2) maternal defensive/aggressive behaviors, mediated by periaqueductal grey (PAG). For humans, the MCN regulates flexible responses to the demands of their own infant during adaptation to the early postpartum period - such as to the unique, ethologically salient own-baby cry. We aim to examine the human MCN and maternal behaviors in a group of opioid-dependent mothers undergoing BT (n=80), as compared to non-opioid using Depression Matched Controls (MC, n=80). All participant will have 2 MRI scans: T1 at 1-month postpartum and T2 at 4-month postpartum. The drug use and moods in all participants will be assessed at these two time points. We will combine multimodal neuroimaging methods, including functional responses to own-baby cry, gray matter volumes and resting state activity with assessments of maternal caregiving thoughts and behaviors – including measures of sensitivity and hostility – at T1 and T2. Based on our preliminary research and preclinical models we hypothesize that BT increases caregiving MCN responses to own vs. other-baby cry and such effects are linked to maternal caregiving thoughts and behaviors. We predict that T1 to T2 plastic adaptation in the MCN will be affected by BT - such that BT may interfere with normally opposing caregiving and defense subsystems of the MCN. Our controls will include recruitment of depression matched participants and statistical control for maternal childhood aversity, polysubstance use and offspring neonatal abstinence syndrome. Finally, we will explore the effects of these factors on brain and maternal behaviors within the group of BT-treated mothers. The proposed research will elucidate the effects of BT on the neurobiology of parenting - with translational potential to optimize current approaches and suggest directions to best manage postpartum mental health issues and improve mother-child bonding and child outcomes - a brain based biomarker.