Maternal Depression Calibrates Infants' Neuroendocrine, Autonomic, and Inflammatory Stress Responsiveness

项目总结 当前提案的目标是确定婴儿的压力反应性何时以及如何通过以下方式进行校准 母亲抑郁，以及这种校正如何转化为儿童的情绪和行为问题。 心理健康依赖于压力反应生理系统的调节--即下丘脑-- 垂体-肾上腺(HPA)轴、自主神经系统(ANS)和炎症介质(IM)反应 符合特定压力源的要求，一旦压力源过去，就会迅速恢复。重要的是要澄清 这些系统如何变得不受监管，以便识别和干预风险轨迹。之前的交叉- 部分研究强调了与一项或多项调控失调有关的母亲预测因素和儿童结局 这些系统，但未能解决这样一种可能性，即人与人之间压力反应能力的发展 系统为了解早期风险提供了一个关键窗口。我们将检验早期接触的核心假设 对母亲抑郁的预测HPA、ANS和/或IM功能的敏感化 通过以下具体目标损害儿童的心理健康：(1)确定是否 母亲抑郁导致跨系统的婴儿压力响应性向上校准；(2)确定 对婴儿压力校正影响最大的母亲抑郁状况；和(3)[表征 通过婴儿应激反应轨迹和婴儿应激反应轨迹之间的关联来研究适应不良应激系统的发展 自我管理职能方面的缺陷。]社区样本[250名孕妇-超过一半的人有 诊断出的严重抑郁发作，其余没有诊断的]-将在怀孕和 在出生后的头两年进行跟踪观察。婴儿在3个月、8个月、15个月和24个月时将暴露在 用唾液皮质醇敲击来评估压力反应性的发展适宜的人际压力源 HPA、α-淀粉酶(SAA)分流ANS，以及IL-1b、IL-6、TNF-a和CRP分流IM的组合物 激活。将通过母亲报告和行为测量来评估儿童的自我调节发展 在24个月的时候。我们假设，母亲的抑郁症状将预测儿童的压力敏感度 3-24个月，证据是随着时间的推移，多系统激活增加/不恢复的轨迹。这个 预期对早期(产前、产后3个月)抑郁症状的母亲的影响最大 已经超过了终生抑郁障碍的诊断门槛。我们进一步预计儿童压力 敏化-[尤其是HPA和IM的高/高一致性激活，但低/减少 HPA和ANS的一致性]--在24岁时会预测执行功能和情绪调节能力较差 月份。实现这些目标将澄清母亲抑郁是如何校准压力反应系统的 以及这种校准如何为以后的紊乱提供风险。这一发现将为人类提供一个真正的发展模式 为母婴早期干预确定新的应激生理学指标时的应激相关调节障碍 以减轻抑郁母亲的子女的心理健康风险。

PROJECT SUMMARY The objective of the current proposal is to determine when and how infants' stress responsivity is calibrated by maternal depression, and how this calibration translates into child emotional and behavioral problems. Psychological health relies on the regulation of stress-responsive physiological systems—i.e., hypothalamic- pituitary-adrenal (HPA) axis, autonomic nervous system (ANS), and inflammatory mediator (IM) responses that match the demands of a given stressor and recover promptly once it has passed. It is important to clarify how these systems become dysregulated in order to identify and intervene on risk trajectories. Previous cross- sectional research highlights maternal predictors and child outcomes related to dysregulation of one or more of these systems but fails to address the possibility that within-person development of stress responsivity across systems offers a critical window into early risk. We will test the central hypothesis that early exposure to maternal depression predicts sensitization of HPA, ANS, and/or IM function that undermines the child's psychological health through the following specific aims: (1) Determine whether maternal depression induces upward calibration of infant stress responsivity across systems; (2) Identify maternal depression profiles with the strongest impact on infant stress calibration; and (3) [Characterize maladaptive stress system development through associations between infant stress response trajectories and deficits in self-regulatory functions.] A community sample of [250 expectant mothers—over half with a diagnosed major depressive episode and the rest with no diagnoses]—will be recruited during pregnancy and followed through the first 2 postnatal years. At 3, 8, 15, and 24 months the infant will be exposed to developmentally appropriate interpersonal stressors to assess stress responsivity, with salivary cortisol tapping HPA, alpha-amylase (sAA) tapping ANS, and a composite of IL-1b, IL-6, TNF-a, and CRP tapping IM activation. Child self-regulatory development will be assessed via both mother-report and behavioral measures at 24 months. We hypothesize that mothers' depression symptoms will predict child stress sensitization from 3-24 months, evidenced by a trajectory of increasing/nonrecovering multi-system activation over time. The strongest effects are expected for early (prenatal, 3-month postnatal) depression symptoms in mothers who have crossed a diagnostic threshold for a lifetime depressive disorder. We further expect child stress sensitization—[especially high/increasing concordant activation across HPA and IM, but low/decreasing concordance across HPA and ANS]—will predict poorer executive function and emotion regulation at 24 months. Achieving these aims will clarify how stress-responsive systems are calibrated by maternal depression and how this calibration confers risk for later disorder. The findings will inform a truly developmental model of stress-related dysregulation while defining novel stress physiology targets for early mother/infant intervention to mitigate psychological health risks in children of depressed mothers.