Timing of prenatal stress and infant regulatory functioning

项目摘要 随着社会寻求了解人类情绪和行为障碍的病因，越来越多的关注 必须关注易患这些疾病的最早决定因素，包括那些存在于 产前生活母亲在怀孕期间的压力通过破坏怀孕的许多方面而导致这种脆弱性。 胎儿发育，包括婴儿后期生理和行为反应的基础， 应力众所周知，这些压力应对系统的失调会使婴儿面临巨大的风险， 情绪和行为问题然而，实际上仍然未知的是， 产前应激影响婴儿对应激的生物行为调节受损程度。上 纵向前瞻性研究，我们建议使用前所未有的高频采样， 测量一个常见的主要压力源的发生在一个队列的335名妇女开始早在第15周， 怀孕，然后准确地确定在怀孕期间（早期，中期，晚期）的压力暴露有 对他们6个月大的婴儿对压力的生理反应影响最大（即，下丘脑-垂体轴 和交感神经系统反应性）和他们对压力的行为反应。产前压力源， 亲密伴侣暴力（IPV）是一个典型的例子。IPV是理想的研究，因为，不像 在以往对产前应激的研究中，研究了多种应激源，IPV是一种极为常见的应激源 孕妇在怀孕期间的经历和时间可以非常精确地评估。 此外，女性可以在怀孕期间，产后或两者兼而有之的情况下经历IPV。因此除了 确定胎儿生命中暴露于这种主要压力源特别有害的关键时期 到后来的婴儿压力反应，我们可以确定这些影响如何与出生后暴露于 相同的压力源基于对参与神经基质发育里程碑的了解， 生理和行为反应的压力，我们假设在目标1，妊娠早期的压力将 对婴儿SNS应激反应性的影响最大，但妊娠中期应激对婴儿SNS应激反应性的影响最大， 对婴儿HPA轴反应性和他们对压力的行为反应的影响。在目标2中，我们将研究 母体HPA轴和SNS在妊娠期间作为产前IPV影响的中介作用， 后期婴儿应激反应。了解产前生活中存在的压力敏感期 这将对精确定位细胞和分子机制产生深远的影响， 胎儿和负责出生后看到的负面结果。这些知识也将大大告知 预防和干预策略，这将有助于避免在此期间压力的负面影响， 人类心理和行为发展的敏感期，从而改善生活 数以百万计的妇女和她们的婴儿。

PROJECT SUMMARY As society seeks to understand the etiology of human emotional and behavioral disorders, increasing attention must focus on the earliest determinants of vulnerability to these disorders, including those existing during prenatal life. Maternal stress during pregnancy contributes to this vulnerability by derailing many aspects of fetal development, including those underlying the infant’s later physiological and behavioral responses to stress. Dysregulation of these stress-coping systems is known to put infants at tremendous risk for later emotional and behavioral problems. What remains virtually unknown, however, is how the differential timing of prenatal stress affects the degree of impairment in infants’ biobehavioral regulation to stress. In the first longitudinal prospective study of its kind, we propose to use unprecedented high-frequency sampling to measure the occurrence of a common major stressor in a cohort of 335 women starting as early as week 15 of pregnancy, and then determine precisely when during pregnancy (early, mid, late) the stress exposure had the greatest impact on their 6-month-old infants’ physiological responses to stress (i.e., hypothalamic-pituitary axis and sympathetic nervous system reactivity) and their behavioral responses to stress. The prenatal stressor we will use as a model is intimate partner violence (IPV). IPV is ideal to study for this purpose because, unlike many stressors studied in previous research on prenatal stress, IPV is an extremely common stressor experienced by pregnant women and its timing during pregnancy can be very precisely assessed. Furthermore, women can experience IPV during pregnancy, postpartum, or both. Therefore, in addition to determining the critical periods during fetal life when exposure to this major stressor is particularly detrimental to later infant stress responsivity, we can determine how those effects compare with postnatal exposure to the same stressor. Based on knowledge about the developmental milestones for the neural substrates involved in the physiological and behavioral responses to stress, we hypothesize in Aim 1 that early gestation stress will have the greatest effects on infant SNS stress responsivity, but that mid-gestation stress will have the greatest effects on infant HPA-axis responsivity and their behavioral responses to stress. In Aim 2 we will examine the maternal HPA axis and SNS functioning during her pregnancy as a mediator of the effects of prenatal IPV on later infant stress responsivity. Knowledge about the sensitive periods to stress that exist within prenatal life will have profound implications for pinpointing the cellular and molecular mechanisms that are derailed in the fetus and responsible for the negative outcomes seen after birth. This knowledge will also greatly inform strategies for prevention and intervention that will help avoid the negative effects of stress during this exquisitely sensitive period for human psychological and behavioral development and, thus, improve the lives of millions of women and their infants.