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：未来患精神疾病和成瘾疾病的风险从生命早期就开始了， 有证据强调子宫内环境的关键作用。 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 我们的研究（妊娠压力，SIP 研究）以及其他人的研究表明，在子宫内暴露。 母亲心理社会压力是恐惧相关和冲动控制相关问题风险的主要预测因素 我们现在已经准备好对我们独特的种族和特征进行长期跟踪。 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 尽管它很重要，但很少有研究表明它与未来的行为障碍和成瘾风险相关。 研究了从生命早期到青春期前/青春期的胎盘分子特征和生物行为评估 我们的初步结果显示，利用 SIP 研究的生物库和深层表型儿童行为。 下丘脑-垂体-肾上腺（HPA）轴和免疫系统的表观遗传变化与 SIP 研究队列中暴露于子宫内母亲压力的儿童的恐惧、焦虑和情绪失调。 有很多优势：从子宫内开始的持续长期随访、多样性（经济和种族）、 广泛存储的生物样本（胎盘、脚趾甲、头发样本）及其准实验设计。 该群体目前正进入青春期前/青春期（9-13 岁），这是快速社会和生物转变的时期，也是一个高峰期 大脑仍在发展认知功能时出现适应不良、冒险行为。 借助这个无与伦比的机会，我们将跟踪该队列：1）检查子宫内接触 SS 的作用以及 产后压力（规范压力、养育）对神经发育功能的影响，通过测量 多项行为、生理和神经心理学评估；2) 确定之间的关系 胎盘中的产前表观基因组特征（以及对 HPA 轴和免疫网络的先验关注） 基因）对负面行为特征（即过度焦虑和破坏性）的后续风险的影响 行为）和执行功能受损，已知会增加过早开始吸毒的风险。 继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 女孩的问题内在化，男孩的问题外化）。我们将进一步探讨的调节作用。 失业状况与产前 SS 压力和产后压力交叉时对个体差异的影响 认知神经行为，这使得青春期前/青春期的儿童更容易受到后续发作的影响 我们将建立我们独特的生物样本和档案存储库。 胎盘中表观基因组和 RNA 表达网络的染色质可及性急剧下降。 不利压力源的发生率增加，特别是自然灾害（例如飓风、野火和流行病）， 研究 SS 应激对从子宫内到胎儿期神经发育的短期和长期影响 青春期前/青春期，将帮助我们发现问题，并可能对母亲和儿童进行重大干预。