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Early Life Adversity, Biological Embedding, and Risk for Developmental Precursors of Mental Disorders

生命早期的逆境、生物嵌入和精神障碍发育先兆的风险

基本信息

批准号：
10744627
负责人：
JOAN L. LUBY
金额：
$ 246万
依托单位：
WASHINGTON 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：
2018-05-22 至 2028-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10744627
关键词：
2 year old 3 year old Adverse effects Affect Age Behavior Behavioral Biological Birth Brain Caregiver support Caregivers Child Childhood Chronic Clinical Cognitive Collection Communities Crime Data Data Collection Development Diagnosis Diffusion Disadvantaged Environment Exposure to Extended Family Family Frequencies Functional Magnetic Resonance Imaging Immune Immunologic Markers Inflammation Inflammatory Inflammatory Response Interleukin-6 Investigation Language Life Link Lipopolysaccharides Longitudinal Studies Magnetic Resonance Imaging Measures Mediating Mediator Meditation Memory Mental disorders Metabolic Pathway Neighborhoods Neonatal Neurons Parents Pathway interactions Phase Pregnancy Prevalence Prevention Psychopathology Reporting Risk Role Sampling School-Age Population Schools Social support Structure Supportive care Surface Symptoms TNF gene Testing Time Variant brain volume caregiving circulating biomarkers clinical risk cognitive development cytokine data repository early childhood early life adversity effector T cell experience gut microbiome in utero inflammatory marker inflammatory milieu mental disorder prevention microbiome microbiome alteration middle childhood monocyte multimodality neighborhood safety neurodevelopment neuroinflammation novel peer peer support prenatal preventive intervention prospective repository resilience resilience factor response risk minimization school environment social social disparities social influence social relationships social structure spectrograph systemic inflammatory response translational potential

项目摘要

PROJECT SUMMARY Early exposure to social disadvantage, specifically family and neighborhood financial disadvantage in utero and through the first 3 years of life, is a powerful and potentially modifiable environmental determinant of risk for childhood psychopathology. The ongoing Early Life Adversity and Biological Embedding (eLABE) study launched in 2017 has aimed to elucidate mechanisms of this risk trajectory and guide preventive interventions. To date, eLABE has detected powerful associations between prenatal social disadvantage and structural and functional brain development at birth which are mediated through elevations in maternal cytokines and alterations in the gut microbiome. These neonatal neurodevelopmental variations have been linked to elevations in markers of psychopathology risk at age 2 years. Further, decreased caregiver nurturance mediated some aspects of this relationship, with supportive caregiving mitigating child psychopathology risk. Our central hypothesis is that pro- inflammatory immune and gut microbiome profiles evident in children exposed to prenatal and early life social disadvantage induce neuronal effects that negatively impact structural and functional brain development leading to increased risk for psychopathology. This renewal proposes to build upon the existing data to continue following our unique and well-characterized sample of 377 children for whom we have assembled a rich, unparalleled repository including comprehensive measures of social disadvantage (in utero and ages 1, 2, and 3 years) with early life measures of inflammation, the gut microbiome, and brain development (structural, microstructural, and functional MRI at birth and ages 2 and 3). In the next phase of eLABE, we propose to follow this sample into school entry (age 6) and middle childhood (age 8), adding assessments of social disadvantage, developmental/behavioral, inflammatory marker, multimodal MRI, and caregiver and social support measures at both timepoints and one additional wave of the gut microbiome at age 6. We will utilize these data to test specific hypotheses about mechanistic pathways to mental disorders that begin to clearly emerge in early childhood and school age, and will utilize novel brain metrics to more directly examine the roles of neuroinflammation and plasticity in this risk pathway. We will also examine the effects of caregiver and family, peer, and school supports on this risk trajectory, including their role as possible resilience factors, and explore whether there are sensitive periods for these effects. The results will provide the first systematic and intensive prospective examination of the relationship of social disadvantage to chronic systemic inflammation, the gut microbiome, and their links to brain development and behavior related to risk for clinical mental disorders. Critically, by targeting caregiving, inflammation, and the gut microbiome as key mechanistic pathways, these data will also have tremendous clinical and translational potential as they investigate potential mediators of risk and provide modifiable targets for prevention of mental disorders.

项目总结

项目成果

期刊论文数量（7）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Disentangling Socioeconomic Status and Race in Infant Brain, Birth Weight, and Gestational Age at Birth: A Neural Network Analysis.

DOI：
10.1016/j.bpsgos.2023.05.001
发表时间：
2024-01
期刊：
Biological psychiatry global open science
影响因子：
0
作者：
通讯作者：

Environmental Conditions to Promote Healthy Childhood Brain/Behavioral Development: Informing Early Preventive Interventions for Delivery in Routine Care.

DOI：
10.1016/j.bpsgos.2021.10.003
发表时间：
2022-07
期刊：
Biological psychiatry global open science
影响因子：
0
作者：
通讯作者：

SSRI use during pregnancy and risk of stillbirth and neonatal mortality.

怀孕期间使用 SSRI 会增加死产和新生儿死亡的风险。

DOI：
10.1176/appi.ajp.2012.11081251
发表时间：
2013
期刊：
The American journal of psychiatry
影响因子：
0
作者：
Jimenez-Solem,Espen;Andersen,JonTrærup;Petersen,Morten;Broedbaek,Kasper;Lander,AndersRune;Afzal,Shoaib;Torp-Pedersen,Christian;Poulsen,HenrikE
通讯作者：
Poulsen,HenrikE

Translating RDoC to Real-World Impact in Developmental Psychopathology: A Neurodevelopmental Framework for Application of Mental Health Risk Calculators.

DOI：
10.1017/s0954579421000651
发表时间：
2021-12
期刊：
Development and psychopathology
影响因子：
3.3
作者：
MacNeill LA;Allen NB;Poleon RB;Vargas T;Osborne KJ;Damme KSF;Barch DM;Krogh-Jespersen S;Nielsen AN;Norton ES;Smyser CD;Rogers CE;Luby JL;Mittal VA;Wakschlag LS
通讯作者：
Wakschlag LS

The Infant Brain: A Critical Antecedent of Psychiatric Risk.

婴儿大脑：精神病风险的关键前因。