A targeted approach to examine the influence of maternal psychological stress on newborn brain outcomes

项目摘要/摘要 孕期母亲心理应激增加与发病风险增加的关系 后代的精神病理学已经被反复证明。有证据表明，边缘-- 前额叶脑系统(LPFS)在心理健康结果中的作用，以及LPFS对早期生活应激的脆弱性。 方法的进步使检查新生儿的LPFS成为可能，提高了分离Pre-Pre的能力 后天的影响。目前的提案在几个关键方面建立在这项工作的基础上。第一，虽然具体 怀孕期间心理压力的特征(如强度、变化性、时机)似乎有 尽管对后代结局有重要影响，但对这一主题的研究得出了不一致的结论。第二, 孕期母体心理应激与母体心理应激的关系 后代的大脑系统仍然相互关联。这项建议寻求增加特异性和推进因果关系。 了解孕期母体心理应激对子代LPFS的影响。 申请者将检查一个独特的、现有的健康母婴二元组的纵向数据集(N=86)。 具有广泛的产前环境和新生儿结构和静息状态功能的特征 连接性磁共振成像(sMRI和rS-fcMRI)。将使用非常合适的分析技术来识别 孕期母亲心理压力(基于4天生态瞬时评估[EMA] 每三个月)与新生儿LPFS关系最密切(K99，目标1)。申请者随后将检查 EMA测量心理压力与基于问卷的压力测量和生物学压力测量的关系 指标(内分泌和免疫/炎症)，以确定资源密集度较低的替代标志物(K99， 目标2)。R00(目标3)将专注于高水平心理水平丰富的孕妇样本 压力。它将采用随机对照试验，对已建立的压力缓解干预(正念-- 基于认知疗法=60，对照研究=60)以检验干预导致母婴减少的假说 心理应激会影响新生儿LPFS。 应聘者在DOHAD，发展神经科学领域拥有独特的背景 和临床科学。在K阶段，她将扩展她的干预研究培训，重点是 对孕妇进行干预，以检验源于DOHaD的假设。国防部的培训将重点放在 学习EMA数据的分析技术，加深对孕期母体压力的理解。 基于她在发育神经科学方面的坚实基础，申请者将获得高级技能 确保她作为一名独立研究员取得成功。导师团队，费尔博士(发展 神经科学)、巴斯(DOHaD)、考伊(临床科学与妊娠)和麦克沃伊(预防 孕期干预)，提供所有核心领域的专业知识，跨越所有职业阶段，并带来 在获得独立资助和指导年轻科学家方面的出色记录。

PROJECT SUMMARY/ABSTRACT Associations between heightened maternal psychological stress during pregnancy and increased risk of offspring psychopathology have been demonstrated repeatedly. Evidence points to the integral role of limbic- prefrontal brain systems (LPFS) in mental health outcomes, and the vulnerability of LPFS to early life stress. Methodological advances allow for examining LPFS in newborn infants, increasing capacity to isolate pre- from postnatal influences. The current proposal builds on this work in several key ways. First, although specific characteristics of psychological stress during pregnancy (e.g. intensity, variability, timing) appear to have important implications for offspring outcomes, research on this topic has yielded inconsistent findings. Second, the framework for understanding associations between maternal psychological stress during pregnancy and offspring brain systems remains correlational. This proposal seeks to increase specificity and advance causal understanding regarding the influence of maternal psychological stress during pregnancy on offspring LPFS. The applicant will examine a unique, existing longitudinal dataset of healthy mother-infant dyads (N=86) with extensive characterization of the prenatal environment and newborn structural and resting state functional connectivity MRI (sMRI and rs-fcMRI). Well suited analytic techniques will be used to identify characteristics of maternal psychological stress during pregnancy (based on 4-days of ecological momentary assessment [EMA] in each trimester) most strongly associated with newborn LPFS (K99, Aim 1). The applicant will then examine EMA measured psychological stress in relation to questionnaire-based stress measures and biological indicators (endocrine and immune/inflammatory) to identify less resource intensive alternative markers (K99, Aim 2). The R00 (Aim 3) will focus on a sample of pregnant women enriched for high levels of psychological stress. It will employ a randomized-controlled-trial of an established stress reduction intervention (Mindfulness- Based Cognitive Therapy=60, Cntrl=60) to test the hypothesis that intervention-induced reduction in maternal psychological stress will influence newborn LPFS. The applicant brings a unique background spanning the fields of DOHaD, developmental neuroscience and clinical science. During the K-phase she will extend her training in intervention research with a focus on intervention with pregnant women to test hypotheses stemming from DOHaD. Training in DOHaD will focus on learning analytic techniques for EMA data, and deepening understanding of maternal stress during pregnancy. Building on her strong foundation in developmental neuroscience, the applicant will gain advanced skills to ensure her success as an independent researcher. The team of mentors, Drs. Fair (developmental neuroscience), Buss (DOHAD), Caughey (clinical science and pregnancy) and McEvoy (preventive intervention during pregnancy), provide expertise in all core areas, span all levels of career stage, and bring an excellent record of obtaining independent funding and mentoring young scientists.