Epigenetic susceptibility of behavioral and addictive disorders during pre/pubescence after natural disaster exposures in-utero

子宫内自然灾害暴露后青春期前/青春期行为和成瘾障碍的表观遗传易感性

• 批准号: 10739665
• 负责人: Yoko Nomura
• 金额: $ 98.65万
• 依托单位: QUEENS COLLEGE
• 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 2028-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10739665
• 关键词: 13 year old; Acceleration; Adolescence; Adrenal Glands; Adverse effects; Affect; Age; Aggressive behavior; Anxiety; Attention; Behavior; Behavior Disorders; Behavioral; Biological; Biological Assay; Birth; Brain; Characteristics; Child; Child Behavior; Child Development; Child Rearing; Childhood; Chromatin; Clinic; Cognitive; Cohort Studies; Data; Development; Dimensions; Discipline of obstetrics; Disease; Emotional; Environment; Epigenetic Process; Executive Dysfunction; Exposure to; Fright; Future; Gene Expression; Genes; Genetic; Genetic Transcription; Goals; Hair; Health; Hurricane; Hydrocortisone; Hypothalamic structure; Immune; Immune system; Impulsivity; Incidence; Individual Differences; Intervention; Investigation; Life; Longitudinal Studies; Longterm Follow-up; Measures; Mental Health; Molecular; Molecular Profiling; Mothers; Natural Disasters; Natural experiment; Neurocognitive; Neuropsychology; Outcome; Parents; Pattern; Phase; Phenotype; Physiological; Pituitary Gland; Placenta; Population Heterogeneity; Positioning Attribute; Predisposition; Pregnancy; Pregnant Women; Problem behavior; Progesterone; Psychosocial Stress; Puberty; Quasi-experiment; Race; Research; Resources; Risk; Risk Marker; Risk Taking; Role; Sampling; Second Pregnancy Trimester; Sex Differences; Social support; Socioeconomic Status; Specimen; Stress; Structure of nail of toe; Substance Use Disorder; Technology; Testing; Testosterone; Time; Transposase; Wildfire; Woman; Work; addiction; behavioral outcome; behavioral phenotyping; biobank; biobehavior; biomarker identification; boys; cognitive development; cognitive function; cohort; cost; dehydroepiandrosterone; demographics; early adolescence; early childhood; early onset substance use; emotion dysregulation; epigenome; excessive anxiety; executive function; fetal programming; gene network; girls; high risk; hypothalamic-pituitary-adrenal axis; in utero; infancy; low socioeconomic status; marijuana use; maternal depression; maternal stress; neurobehavior; neurobehavioral; neurodevelopment; offspring; pandemic disease; postnatal; prenatal; prenatal exposure; prenatal stress; psychosocial; public health relevance; recruit; repository; response; sex; social; socioeconomics; steroid hormone; stress reactivity; stressor; study population; transcriptome sequencing

Summary/Abstract: The risk for developing future psychiatric and addiction disorders starts early in life, with evidence emphasizing the critical contribution of the in utero environment. Maternal psychosocial stress has a significant impact on the prenatal environment and contributes to negative health and neurobehavioral outcomes in offspring. Our research (Stress in Pregnancy, SIP study), along with that of others, has shown that in utero exposure to maternal psychosocial stress is a major predictor of the risk for fear-related and impulse control-related problems during early childhood. We are now well positioned to conduct a long-term follow-up of our unique racially and financially diverse SIP study population to identify biomarkers of children’s behavior and physiological reactivity relevant for future subsequent behavioral disorders and addictive risk. Despite its importance, few studies have investigated placental molecular signatures to bio-behavioral assessments from early life through the pre/pubertal phase. Exploiting the SIP study's bio-repositories and deep-phenotyped child behaviors, our preliminary results show that epigenetic changes of the hypothalamic-pituitary-adrenal (HPA) axis and immune systems are associated with fear, anxiety, and emotion dysregulation among children exposed to in utero maternal stress. The SIP study cohort has many strengths: its consistent long-term follow-up, from in utero, its diversity (financially and racially), its extensive repository of stored biospecimens (placenta, toenail, hair samples), and its quasi-experimental design. The cohort is now entering pre/puberty (ages 9-13), a time for rapid social and biological transition and a peak time for the emergence of maladaptive, risk-taking behaviors with the brain still developing cognitive functions. Using this unparalleled opportunity, we will follow the cohort to 1) examine the role of exposure to SS in utero along with the effect of postnatal stress (normative stress, parenting) on neurodevelopmental functioning, as measured by multiple behavioral, physiological, and neuropsychological assessments; 2) determine the relationship between the prenatal epigenome signature in the placenta (along with an a priori focus on the HPA-axis and immune network genes) on the subsequent risk for negative behavioral characteristics (i.e., excessive anxiety and disruptive behaviors) and impaired executive functioning, known to elevate the risk for early initiation of substance use. Following our prior work, we will also examine sex-specific manifestations of the behavioral phenotypes (more internalizing problems in girls and externalizing in boys). We will further explore the moderating role of socioeconomic status when intersecting with prenatal SS-stress and postnatal stress on individual differences in cognitive neuro-behaviors, which make pre/pubescent children more vulnerable for a subsequent onset of behavioral and addictive disorders. We will build on our unique repository of stored biospecimens and profile chromatin accessibility across the epigenome and RNA expression network in the placenta. Given the steeply increasing incidence of adverse stressors, especially natural disasters (e.g., hurricanes, wildfires and pandemics), investigation of the short- and long-term impact of SS-stress on neurodevelopment from in utero through pre/puberty, will help us to identify problems and potentially lead to significant interventions for mother and child.

摘要/摘要：发展未来精神和成瘾性疾病的风险始于生命的早期， 强调子宫内环境的关键作用的证据。母亲的心理社会压力 对产前环境产生重大影响，并导致不良的健康和神经行为结果， 后代我们的研究（妊娠期压力，SIP研究），沿着其他人的研究表明，子宫内暴露 母亲的心理社会压力是一个主要的预测风险的恐惧相关和冲动控制相关的问题 在童年早期。我们现在已经做好了充分的准备，可以对我们独特的种族和 经济上多样化的SIP研究人群，以确定儿童行为和生理反应的生物标志物 与未来后续行为障碍和成瘾风险相关。尽管它很重要，但很少有研究 研究了从生命早期到青春期前的胎盘分子特征和生物行为评估。 相位利用SIP研究的生物储存库和深度表型儿童行为，我们的初步结果显示， 下丘脑-垂体-肾上腺（HPA）轴和免疫系统的表观遗传变化与 暴露于宫内母亲压力的儿童中的恐惧、焦虑和情绪失调。SIP研究队列 它有许多优点：从子宫内开始的长期随访，多样性（经济和种族）， 储存生物样本（胎盘、脚趾甲、毛发样本）的广泛储存库及其准实验设计。 该群体现在正进入青春期前/青春期（9-13岁），这是一个快速的社会和生物过渡时期，也是一个高峰期。 在大脑认知功能还在发育的情况下出现适应不良和冒险行为。使用 这个无与伦比的机会，我们将跟踪队列1）检查子宫内暴露于SS的作用，沿着 产后压力（正常压力，养育）对神经发育功能的影响，通过以下指标测量： 多种行为、生理和神经心理评估; 2）确定 胎盘中的产前表观基因组标记（沿着先验地关注HPA轴和免疫网络 基因）对负面行为特征的后续风险（即，过度焦虑和破坏性 行为）和执行功能受损，已知会增加早期开始使用药物的风险。 在我们之前的工作之后，我们还将检查行为表型的性别特异性表现（更多 女孩的内在问题和男孩的外在问题）。我们将进一步探讨 社会经济状况时，交叉与产前SS压力和产后压力的个体差异， 认知神经行为，这使得青春期前/青春期儿童更容易受到随后发病的影响。 行为和成瘾性障碍。我们将建立在我们独特的储存生物标本和档案库的基础上， 胎盘中表观基因组和RNA表达网络的染色质可及性。鉴于陡峭的 不利的压力源，特别是自然灾害（例如，飓风、野火和流行病）， SS-应激对子宫内至胎儿期神经发育的短期和长期影响的研究 青春期前/青春期，将有助于我们发现问题，并可能导致对母亲和儿童的重大干预。