Maternal Childhood Maltreatment-Influenced Prenatal Programming of Early Brain-Behavior and Risk for Future Psychopathology

母亲童年虐待影响的早期大脑行为的产前编程和未来精神病理学的风险

• 批准号: 10740663
• 负责人: Vanessa Babineau
• 金额: $ 13.08万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10740663
• 关键词: Address; Adult; Affect; Amygdaloid structure; Anxiety; Anxiety Disorders; Award; Behavioral; Biological; Biometry; Black race; Brain; Brain imaging; Child; Child Abuse and Neglect; Child Rearing; Childhood; Conceptions; Data; Data Set; Development; Early Intervention; Emotional; Family dynamics; Functional Magnetic Resonance Imaging; Future; Generations; Goals; Health; Health behavior; Hispanic; Image; Indigenous; Infant; Infant Behavior; Infant Health; Intervention; Knowledge acquisition; Laboratories; Lead; Left; Literature; Magnetic Resonance Imaging; Mediating; Mediation; Mediator; Mental Depression; Mental Health; Mothers; Motor Cortex; Network-based; Newborn Infant; Outcome; Participant; Pathway interactions; Pattern; Perinatal; Play; Population; Postpartum Depression; Prefrontal Cortex; Pregnancy; Psychology; Psychopathology; Reporting; Research; Research Domain Criteria; Rest; Risk; Role; Sampling; Science; Scientist; Shapes; Smiling; Stress; Structure of superior frontal gyrus; Technical Expertise; Teenagers; Testing; Training; Trauma; United States; abuse neglect; archived data; biological sex; brain behavior; career; clinical application; clinically relevant; emotion regulation; executive function; experience; imaging study; in utero; infant outcome; interdisciplinary approach; intergenerational; multimodality; next generation; novel; perinatal mental health; postnatal; prenatal; prenatal influence; programs; psychologic; psychosocial; risk mitigation; social; social health determinants; socioeconomics; theories; transmission process

PROJECT SUMMARY The proposed research aims will provide support for a novel pathway of intergenerational trauma through new- born amygdala network connectivity programmed in utero influencing infant emotion regulation problems that may lead to less optimal mother-infant interactions (e.g., disorganized attachment), resulting in increased risk for psychopathology. The proposed training will add to the applicants’ background in perinatal psychology and developmental psychopathology to include needed training in newborn brain imaging and enable their future independent career as a clinician-scientist with expertise in novel pathways of intergenerational trauma through in utero programming of early brain-behavior leading to increased risk for psychopathology, informing critical malleable windows for early intervention. In one study, 40% of children developed anxiety disorders when their mother experienced childhood maltreatment (MCM), as compared to only 24% in the absence of MCM. Most known pathways of transmission are behavioral, with limited evidence for biological transmission. Well-estab- lished behavioral pathways are through maternal psychological state and parenting sensitivity influencing infant emotion regulation and mother-infant attachment. Emerging evidence supports MCM effects on infant out- comes through biological pathways such as in utero programming of brain development, e.g., MCM was asso- ciated with greater newborn resting-state functional connectivity (rsFC) between the amygdala and regions of the prefrontal cortex (PFC) and key brain networks implicated in stress processing. However, associations be- tween MCM-influenced alterations in amygdala network connectivity with infant behavior or child outcomes have yet to be established, limiting the clinical application of emergent literature. The candidate will address a critical gap in the literature by investigating a novel biological pathway of intergenerational trauma: MCM-influ- enced prenatal programming shaping newborn amygdala network connectivity prior to postnatal influences (i.e., substantiating prenatal programming of MCM transmission), in association with infant emotion regulation problems (i.e., making emergent research more clinically relevant), resulting in increased risk for psychopathol- ogy. Mediators and moderators will also be considered, such as maternal prenatal psychological state, psycho- social health, health behaviors, social determinants of health, infant health, and infant biological sex. The appli- cant will obtain training in newborn functional magnetic resonance imaging (fMRI), laboratory observational assessment of infant behavior, theory and science of intergenerational trauma, and biostatistics. The K99/R00 will inform the candidate’s first R01 proposal with specific hypotheses about brain circuits associated with in- fant emotion regulation problems and disorganized attachment as RDoC informed indicators of future risk for child psychopathology, and guide decisions for obtaining subsequent fMRI and interdisciplinary longitudinal multi-level assessment. Future R01s will build a research program to investigate novel pathways of intergener- ational trauma through early brain-behavior programmed in utero leading to changes in infant and child social- emotional development and family dynamics, with mediators and moderators prior to and throughout preg- nancy, to help mitigate risk for intergenerational transmission of trauma and psychopathology. The K99/R00 will culminate in a successful transition to career independence.

项目摘要 拟议的研究目标将通过新的方法为代际创伤的新途径提供支持， 出生杏仁核网络连接在子宫内编程影响婴儿情绪调节问题， 可能导致不太理想的母婴相互作用（例如，混乱的依恋），导致风险增加 精神病理学拟议的培训将增加申请人的围产期心理学背景， 发展精神病理学，包括新生儿脑成像所需的培训，使他们的未来 作为一名临床科学家的独立职业，他在代际创伤的新途径方面具有专业知识， 子宫内早期大脑行为编程导致精神病理学风险增加， 可延展的窗口，以便进行早期干预。在一项研究中，40%的儿童在他们的父母的帮助下患上焦虑症。 母亲经历过童年虐待（MCM），相比之下，只有24%，在没有MCM。最 已知的传播途径是行为传播，生物传播的证据有限。好-estab- 母亲的心理状态和亲职敏感性是影响婴儿行为的主要途径 情绪调节和母婴依恋。新出现的证据支持MCM对婴儿出生的影响- 通过生物学途径，如在子宫内编程的大脑发育，例如，MCM是阿索- 与杏仁核和杏仁核区域之间更大的新生儿静息状态功能连接（rsFC）有关。 前额叶皮层（PFC）和与压力处理有关的关键大脑网络。但是，协会应- 杏仁核网络连接中受MCM影响的改变与婴儿行为或儿童结局之间的关系 尚未建立，限制了紧急文献的临床应用。候选人将在一个 通过调查代际创伤的一种新的生物学途径：MCM-influ， 在出生后影响之前，加强产前编程塑造新生儿杏仁核网络连接 (i.e.,证实MCM传播的产前编程），与婴儿情绪调节有关 问题（即，使紧急研究更具临床相关性），导致精神病理学风险增加- 奥吉。还将考虑调解人和调解人，如产妇产前心理状态，心理， 社会健康、健康行为、健康的社会决定因素、婴儿健康和婴儿生物性别。应用程序- cant将获得新生儿功能性磁共振成像（fMRI）的培训，实验室观察 婴儿行为评估、代际创伤理论和科学以及生物统计学。K99/R00 将告知候选人的第一个R 01建议与大脑回路相关的具体假设， 情绪调节问题和混乱的依恋作为RDoC告知未来风险的指标， 儿童精神病理学，并指导决定获得随后的功能磁共振成像和跨学科的纵向 多层次评估。未来的R 01将建立一个研究计划，以调查新的途径， 在子宫内编程的早期大脑行为造成的民族创伤，导致婴儿和儿童社会- 情绪发展和家庭动态，与调解人和主持人之前和整个怀孕， 帮助减轻创伤和精神病理学代际传播的风险。K99/R00 最终将成功过渡到职业独立。