Neurobiology of Mothering and Infant Stress

描述(申请人提供)：儿童时期的逆境占人口的50%-75%，可归因于酗酒、吸毒、抑郁和自杀。最近的工作也记录了儿童期虐待对成人神经生物学的持久影响，包括皮质和边缘结构的改变以及HPA轴介导的应激反应的重新编程。然而，值得注意的是，对慢性童年逆境的潜在神经生物学后遗症如何塑造成人照顾婴儿的重要活动，以及这反过来如何影响早期大脑发育的理解。拟议的研究计划首次寻求将神经生物学、神经内分泌和行为水平的过程联系起来，以检查早期逆境的影响是如何在150名母亲和他们的婴儿之间传递给母亲和孩子的。为了实现这些目标，该计划由多名首席调查人员领导，他们在以下方面具有特定的专业知识：(1)母婴沟通；(2)儿童期虐待的神经生物学效应；(3)新生儿神经成像。这项研究的第一个目的是评估与逆境相关的结构、功能或连接性的变化 对于压力调节至关重要的母体大脑区域，包括杏仁核、海马体/下丘脑和内侧眶前皮质(MOFC)，与在扫描仪内心理社会应激挑战中母体应激反应的差异有关。第二个目的是评估童年逆境是否与母亲在4个月和12个月大时与婴儿互动的差异有关。最后，我们将纵向评估母亲沟通中断导致婴儿压力调节受损、杏仁核肥大和一岁时功能连接改变的程度。一项子研究还将评估产前因素的贡献，包括急性和慢性应激激素措施、母亲的精神症状和伴侣冲突。童年逆境和父母教养中断是许多医疗和精神疾病的根本原因，包括成瘾，这些疾病导致数十亿美元的医疗保健支出。对潜在机制、关键时间点和中介因素的详细了解对于设计有针对性的干预措施以抢占早期逆境的不利后果是必要的。拟议的研究计划将提供有关婴儿风险的潜在早期生物标记物的数据，这些标记物比广泛的母亲心理社会因素更具体，并可能导致更早和更有效地识别和干预与风险相关的发育轨迹。

DESCRIPTION (provided by applicant): Childhood adversity accounts for 50-75% of the population attributable risk for alcoholism, drug abuse, depression, and suicide. Recent work has also documented enduring effects of childhood maltreatment on adult neurobiology, including alterations in cortical and limbic structures and reprogramming of HPA-axis mediated stress responses. Notably missing, however, is an understanding of how the potential neurobiological sequelae of chronic childhood adversity shape the vital adult activity of caring for an infant, and how this in turn affects early brain development. The proposed program of research seeks, for the first time, to link processes across neurobiological, neuroendocrine, and behavioral levels to examine how the impact of early adversity is conveyed from mother to child, among 150 mothers and their infants. To accomplish these aims the program is led by multiple principal investigators with specific expertise in: (1) mother-infant communication; (2) neurobiological effects of childhood abuse and (3) neonatal neuroimaging. The first aim of the study is to assess whether adversity- related alterations in structure, function or connectivity of maternal brain regions critical to stress regulation, including the amygdala, hippocampus/subiculum, and medial orbitofrontal cortex (MOFC), are associated with differences in maternal stress response during an in-scanner psychosocial stress challenge. The second aim is to assess whether childhood adversity is associated with differences in mother's interactions with their infants at 4 and 12 months of age. Finally, we will assess longitudinally the degree to which maternal disrupted communication leads to impairments in infant stress regulation, amygdala hypertrophy and altered functional connectivity at one year of age. A substudy will also evaluate the contribution of prenatal factors including acute and chronic stress hormone measures, maternal psychiatric symptomatology and partner conflict. Childhood adversity and disrupted parenting are the root preventable causes for a host of medical and psychiatric disorders including addiction that result in billions of dollars in health care expenditures. A detailed understanding of underlying mechanisms, critical time points, and mediating factors is necessary to design targeted interventions to preempt the adverse consequences of early adversity. The proposed program of research will provide data on potential early biomarkers for infant risk that are much more specific than broad maternal psychosocial factors and could lead to earlier and more effective identification of, and intervention in, risk-related developmental trajectories.