Neurobiology of Mothering and Infant Stress

描述（由申请人提供）：儿童期逆境占酗酒，药物滥用，抑郁症和自杀的人口归因风险的50 - 75%。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，包括皮质和边缘系统结构的改变以及HPA轴介导的应激反应的重新编程。然而，值得注意的是，缺乏对慢性童年逆境的潜在神经生物学后遗症如何塑造照顾婴儿的重要成人活动的理解，以及这反过来又如何影响早期大脑发育。拟议的研究计划首次将神经生物学，神经内分泌和行为水平的过程联系起来，以研究早期逆境的影响如何从母亲传递给150名母亲及其婴儿。为了实现这些目标，该计划由多名主要研究人员领导，他们在以下方面具有特定的专业知识：（1）母婴沟通;（2）儿童虐待的神经生物学影响和（3）新生儿神经成像。这项研究的第一个目的是评估是否逆境相关的结构，功能或连接的变化， 母体大脑区域对压力调节至关重要，包括杏仁核、海马/下托和内侧眶额皮质（MOFC），与在扫描仪内心理社会压力挑战期间母体压力反应的差异相关。第二个目的是评估童年逆境是否与母亲与4个月和12个月大的婴儿互动的差异有关。最后，我们将纵向评估在何种程度上，母亲中断通信导致的损害，婴儿压力调节，杏仁核肥大和改变功能连接在一岁。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的措施，产妇精神病学和合作伙伴的冲突。童年的不幸和父母的破坏是一系列医疗和精神疾病的根本可预防的原因，包括成瘾，导致数十亿美元的医疗保健支出。详细了解潜在的机制，关键的时间点，和调解因素是必要的，以设计有针对性的干预措施，先发制人的不利后果的早期逆境。拟议的研究计划将提供有关婴儿风险的潜在早期生物标志物的数据，这些生物标志物比广泛的孕产妇心理社会因素更为具体，并可能导致更早，更有效地识别和干预与风险相关的发展轨迹。

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.