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The Impact of Maternal Obesity and Poor Antenatal Nutrition on Offspring RDoC Dimensions and Risk for Neurodevelopmental Disorders

母亲肥胖和产前营养不良对后代 RDoC 维度和神经发育障碍风险的影响

基本信息

批准号：
10176597
负责人：
JOEL T NIGG
金额：
$ 76.05万
依托单位：
OREGON HEALTH & SCIENCE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-08-15 至 2023-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10176597
关键词：
3-Dimensional Address Age-Months Animal Model Attention Attention deficit hyperactivity disorder Behavior Behavioral Birth Blood Blood Circulation Brain Buffers Caregivers Child Child Mental Health Coupled Development Diet Dimensions Environment Essential Amino Acids Exposure to Fetal Development Gestational Diabetes Glucose Goals Healthcare Hormonal Hormones Human Human Development Hypertension Impaired cognition Impairment Incidence Infant Infant Behavior Inflammation Inflammatory Insulin Intake Justice Kynurenine Learning Leptin Life Link Measurement Mediator of activation protein Mental disorders Metabolic Metabolic hormone Modeling Negative Valence Neurodevelopmental Disorder Neurotransmitters Nutrient Nutritional Obesity Omega-3 Fatty Acids Outcome Pathway interactions Positive Valence Pregnancy Proteins Psychopathology Research Domain Criteria Risk Route Saturated Fatty Acids Serotonin Shapes Social Processes Symptoms System Temperament Testing Time Toddler Translating Tryptophan Unhealthy Diet Up-Regulation Validation Work antenatal cognitive control cognitive system cytokine design epidemiology study experience family burden human data human study in utero maternal obesity mother nutrition negative affect nonhuman primate novel novel strategies nutrition offspring postnatal prenatal prenatal exposure prevent programs prospective social

项目摘要

PROJECT SUMMARY The goal of this proposal, is to discover prenatal determinants of post-natal behavioral precursors, emerging in the first 36 months after birth, of neurodevelopmental and psychiatric disorders. Epidemiological studies have demonstrated an association between developmental exposure to maternal obesity, gestational diabetes, and hypertension and increased incidence of neurodevelopmental disorders; however, the mechanisms for this association remain largely unknown. Our own work, using non-human primate models, demonstrates causal effects on offspring temperament, operating via changes in inflammation and neurotransmitter synthesis and relate behaviorally to negative valence, supporting the timeliness of a more focused, prospective human study to isolate potential mechanisms. From the RDoC perspective, we therefore prioritize the negative valence domain, which our conceptual framework also places as central to developmental risk in very early life. We also secondarily consider key modulating domains, including positive valence, social processes, and cognitive systems. Working from a liability x experience model, and considering emerging concepts of developmental programming, we highlight two powerful but insufficiently understood environmental inputs in early development: maternal obesity and poor antenatal nutrition. We hypothesize that maternal obesity and poor nutrition alter the in-utero milieu that offspring are exposed to during fetal development resulting in increased exposure to inflammatory factors. Those, in turn, alter brain development (not directly evaluated here) and ultimately behavior (which we study carefully). The overarching hypothesis is that increased exposure to inflammatory factors during fetal development predicts alterations in infant negative valence, shaping a cascade of behavioral development that increases the outcomes related to ADHD, irritability, and behavioral risk for psychiatric disorder. To address this hypothesis, a powerful yet novel combination of a well-established infant/toddler behavioral characterization is coupled with detailed measurements of the nutritional, metabolic, inflammatory, and hormonal profile of the in-utero environment. We also examine selected postnatal moderators and other relevant RDoC-dimensions, in line with our model. Aim 1 evaluates the extent to which in humans' developmental exposure to maternal obesity and/or poor maternal nutrition predicts offspring infant and toddler behavior, in particular negative affectivity. Aim 2 examines changes in the in-utero environment induced by maternal obesity and poor nutrition and tests the hypothesis that increased exposure to inflammation during development underlies the behavioral changes in the offspring. Aim 3 examines the hypothesis that the programming of offspring behavior via maternal obesity-induced inflammation is moderated by the nutrients and hormones that offspring are exposed to during fetal development. Results will clarify mechanistic routes to psychopathology.

项目总结