Opioids and Maternal Brain-Behavior Adaptation During the Early Postpartum

阿片类药物与产后早期母亲大脑行为适应

基本信息

批准号：
10450843
负责人：
James Edward Swain
金额：
$ 70.89万
依托单位：
STATE UNIVERSITY NEW YORK STONY BROOK
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-30 至 2025-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10450843
关键词：
Adaptive Behaviors Affect Amygdaloid structure Anxiety Base of the Brain Behavior Behavioral Biological Markers Brain Brain imaging Brain scan Buprenorphine Caring Child Child Abuse and Neglect Child Rearing Code Coupled Data Disinhibition Dose Drug usage Emotional Epidemic Family Foundations Globus Pallidus Gold Grant Hostility Human Hypothalamic structure Image Impairment Infant Infant Development Insula of Reil Interpersonal Relations Intervention Link MRI Scans Maternal Behavior Measures Medial Mediating Mental Depression Mental Health Methods Modeling Mood Disorders Moods Mothers Neonatal Abstinence Syndrome Neurobiology Nucleus Accumbens Opiate Addiction Opioid Outcome Output Parents Participant Perinatal Physiology Postpartum Period Postpartum Women Pre-Clinical Model Pregnant Women Preoptic Areas Questionnaires Research Resolution Rest Risk Severities Societies Thinking Ursidae Family Ventral Tegmental Area Withdrawal Withdrawal Symptom Woman Work base behavior influence brain behavior brain magnetic resonance imaging buprenorphine treatment caregiving child bearing clinical decision-making comorbid depression comorbidity comparison group cost design dosage dyadic interaction flexibility foster care gray matter high risk illicit opioid imaging study improved maternal caregiving midbrain central gray substance multimodal neuroimaging multimodality non-opioid analgesic offspring opioid epidemic opioid use opioid use disorder polysubstance use pre-clinical pre-clinical research prevent recruit relating to nervous system response social translational potential

项目摘要

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.

项目概要 R01 DA047336-01：产后早期阿片类药物和母亲大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且具有破坏性的流行病，影响了很多人育龄妇女的比例，其中许多人患有未经治疗的阿片类药物使用和共病情绪障碍。依赖性可能会导致戒断症状，损害人际交往，并可能与多物质使用和新生儿戒断综合症（NAS）这些问题与较高的风险有关。虐待儿童和昂贵的寄养服务可减少戒断症状。以及非法阿片类药物对围产期妇女的其他有害影响。 OUD 背景下的母亲神经生物学和婴儿导向行为尚不清楚。母亲大脑行为研究和人脑磁共振成像（MRI）研究提供了用于养育行为的皮质边缘母亲护理神经回路（MCN）模型。两个相互抑制的子系统，用于（1）产妇护理，由内侧视前区介导下丘脑、腹侧被盖区、伏隔核和腹侧苍白球；以及（2）母体防御；对于人类来说，MCN 调节对其需求的灵活反应。自己的婴儿——例如独特的、在道德上显着的自己的婴儿的哭声——在产后早期。旨在检查一组接受 OUD BT 的母亲的人类 MCN 和母亲行为 (n=80) 与非 OUD 抑郁症匹配对照（MC，n=80）相比，所有参与者都将接受 2 次 MRI 扫描：T1。产后 1 个月和产后 4 个月 T2 我们将测量母亲的想法和行为 – 包括针对婴儿的护理和防御措施，以及所有参与者的多物质使用和情绪。我们将使用多模态神经影像方法来测量静息态功能连接、神经对自己婴儿哭声的反应以及 MCN 的灰质体积。我们追求的临床前模型表明，OUD 中的 BT 可以增加护理和防御方面的活动 MCN 的子系统并减少这些子系统之间的正常相互抑制，从而产生最后，我们将探讨母婴导向的防御性思想和行为的潜在去抑制。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，控制了多物质使用和 NAS 的提议。研究将阐明在 OUD 背景下 BT 对养育子女的神经生物学的影响优化当前治疗 OUD 母亲的方法的转化潜力，并提出最佳方向管理产后心理健康问题。