Neurobiology of care giving in opioid dependent mothers

阿片类药物依赖母亲护理的神经生物学

• 批准号: 9404736
• 负责人: DANIEL D LANGLEBEN
• 金额: $ 20.65万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-06-15 至 2019-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9404736
• 关键词: Abstinence; Adherence; Adolescent; Affect; Age; Agonist; Appearance; Appointment; Behavior; Brain; Brain imaging; Breastfed infant; Caring; Characteristics; Child; Child Abuse and Neglect; Child Development; Child Rearing; Childhood; Clinic; Clinical; Cocaine; Complex; Cues; Data; Discipline; Disease remission; Enrollment; Epidemic; Exhibits; Exposure to; Eye; Face; Family; Forehead; Functional Magnetic Resonance Imaging; Goals; Head; Heroin Abuse; Human; Imaging technology; Impairment; Incidence; Infant; Instinct; Interpersonal Relations; Investigation; Knowledge; Literature; Maintenance; Maternal Behavior; Measures; Mediating; Methadone; Mothers; Motivation; Neurobiology; Nucleus Accumbens; Nulliparity; Opiate Addiction; Opioid; Opioid Receptor; Outcome; Oxytocin; Pathologic; Pharmaceutical Preparations; Pharmacotherapy; Play; Portraits; Preventive Intervention; RNA Interference; Research; Rewards; Rodent; Role; Science; Severities; Socialization; Specificity; Stimulus; System; Testing; Therapeutic; Thinking; Time; Translating; Vasopressins; Ventral Striatum; Visit; Visual; Woman; addiction; base; caregiving; cognitive neuroscience; emotional neglect; endogenous opioids; experimental study; falls; follow-up; foster care; high risk; imaging modality; imaging study; improved; indexing; infancy; intergenerational; juvenile animal; maternal caregiving; medication-assisted treatment; motivated behavior; multidisciplinary; neurobiological mechanism; opioid abuse; opioid misuse; opioid use; opioid use disorder; personalized medicine; phenomenological models; physical neglect; postnatal; pre-clinical; preclinical study; prevent; prospective; reinforcer; relating to nervous system; reproductive; response; skills; social; social attachment; standard of care; stem; treatment program; treatment response

Abstract: The opioid dependence (OD) epidemic in the US affects a high proportion of women of reproductive age. OD impairs interpersonal interactions including parenting. Mothers with OD exhibit caregiving deficits leading to child maltreatment, high utilization of foster care, and intergenerational perpetuation of OD. Importance of maternal OD as treatment target is further increased because, unlike cocaine where abstinence is the goal, the recommended treatment for maternal OD is agonist maintenance, which entails continued exposure to exogenous opioids after remission. Yet, while opioid abuse and dependence are at an all time high, knowledge on the phenomenology and neurobiological correlates of maternal behaviors in OD is profoundly underrepresented in the literature. Infantile cues elicit motivation for caregiving in healthy people, even if they’re unrelated to the child. Functional magnetic resonance imaging (fMRI) studies show that this behavior may be conveyed by the mesocorticolimbic (MCL) system, which includes the nucleus accumbens (NAcc) and mediates motivation and reward. “Baby schema”, a set of juvenile features (e.g. large head and big eyes), is perceived as “cute”, elicits motivation for caregiving, and parametrically activates the NAcc in healthy unrelated nulliparous women. These findings suggest that baby schema is what makes babies “cute” and is the natural reinforcer that initiates caregiving behaviors through the MCL system. Preclinical data indicate that (1) endogenous opioids enable maintenance of social bonds including maternal attachment and (2) exogenous opioid agonists cause complex changes in maternal caregiving. Our preliminary data show reduced brain response to baby schema in heroin abusing women, suggesting that these preclinical observations may extend to humans. Our project will prospectively evaluate the brain response to baby schema as a probe of caretaking in mothers with babies who are enrolled in a methadone medication-assisted treatment (MAT) for opioid dependence. Building on the limited largely preclinical data from multiple disciplines and our preliminary fMRI studies in healthy and OD women, we hypothesize that the baseline brain fMRI response to baby schema in OD mothers will be lower than in controls and predict quality of parenting and child development at a six-month follow up visit. These data would enable further research on the markers of vulnerability to caregiving deficits in OD mothers and science-based preventive interventions aimed at improving parenting skills in OD mothers, which could be extended to other substances. This high-risk research has the potential to change the current thinking and practice on the effects of opioid agonists on maternal behaviors, and is a timely contribution to the efforts to stem the ongoing opioid abuse epidemic.

摘要：阿片类药物依赖(OD)在美国的流行影响了很高比例的育龄妇女 年龄。过量服药会损害人与人之间的互动，包括育儿。患有强迫症的母亲表现出照顾能力不足 导致虐待儿童、寄养服务利用率高以及代际持续吸毒。 母体吸食过量作为治疗目标的重要性进一步增加，因为与可卡因不同的是， 是目标，建议对孕产妇OD的治疗是激动剂维持，这需要继续 缓解后接触外源性阿片类药物。然而，尽管阿片类药物滥用和依赖一直存在 高，知识的现象学和神经生物学的相关母亲的行为在OD 在文学作品中的代表性严重不足。在健康的人中，婴儿暗示激发了照顾他人的动机， 即使他们和孩子没有血缘关系。功能磁共振成像(FMRI)研究表明，这 行为可能通过包括伏隔核在内的中皮质边缘系统(MCL)来传递 (NACC)，并调节动机和报酬。“婴儿图式”，一组青少年特征(如大头和大 眼睛)，被认为是“可爱的”，激发照顾的动力，并通过参数激活健康的NAcc 没有血缘关系的未分娩妇女。这些发现表明，婴儿图式是让婴儿变得“可爱”的原因，也是 通过MCL系统启动照顾行为的天然增强剂。临床前数据表明：(1) 内源性阿片类药物能够维持社会纽带，包括母性依恋和(2)外源性 阿片类激动剂会导致母亲护理方面的复杂变化。我们的初步数据显示大脑减少 海洛因滥用妇女对婴儿模式的反应，提示这些临床前观察可能会延伸 对人类来说。我们的项目将前瞻性地评估大脑对婴儿图式的反应，作为照看孩子的一种探索 参加美沙酮阿片类药物辅助治疗(MAT)的婴儿的母亲 依赖。建立在来自多个学科的有限的大部分临床前数据和我们初步的fMRI基础上 对健康和肥胖女性的研究，我们假设基线大脑fMRI对婴儿模式的反应在 母亲的体重将低于对照组，并预测六个月后的育儿质量和孩子的发展 跟踪访问。这些数据将使进一步研究照看缺陷的易感性标志 以提高母亲的育儿技能为目标的以科学为基础的预防干预， 它可以扩展到其他物质。这项高风险的研究有可能改变目前的 关于阿片类激动剂对母亲行为影响的思考和实践，是对 努力遏制目前的阿片类药物滥用流行。