Maternal Inflammation During Pregnancy: Clinical and Neurocognitive Outcomes in Adult Offspring

怀孕期间母体炎症：成年后代的临床和神经认知结果

• 批准号: 10600865
• 负责人: LAUREN M ELLMAN
• 金额: $ 60.74万
• 依托单位: TEMPLE UNIV OF THE COMMONWEALTH
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10600865
• 关键词: Adolescence; Adolescent; Adult Children; Bipolar Disorder; Birth; Brain; Brain imaging; Characteristics; Child Development; Child Health; Childhood; Clinical; Cognitive; Cohort Studies; DSM-V; Data; Development; Diagnosis; Dimensions; Disease; Epidemiology; Exposure to; Fetal Development; Hospitalization; Infection; Inflammation; Intervention; Interview; Laboratories; Link; Longevity; Magnetic Resonance Imaging; Mental Depression; Mental disorders; Methods; Neurocognitive; Neurological outcome; Neuropsychological Tests; Outcome; Participant; Positioning Attribute; Pregnancy; Pregnancy Trimesters; Prevention strategy; Psychiatric Diagnosis; Questionnaires; Random Allocation; Rest; Rewards; Risk; Role; Sampling; Schizophrenia; Second Pregnancy Trimester; Selection Bias; Structure; Symptoms; Time; Woman; brain abnormalities; cognitive function; cohort; cytokine; depressive symptoms; design; feature detection; follow-up; imaging study; in utero; indexing; middle age; multimodality; neural; neurobehavioral; neurodevelopment; neuroimaging; novel; offspring; postnatal; prenatal; prenatal exposure; prenatal influence; psychotic; psychotic symptoms; reward processing; schizophrenia risk; symptom cluster; therapy development; treatment strategy

Project Summary/Abstract This is a resubmission of an application that aims to investigate how maternal inflammation during pregnancy influences clinical, neurocognitive, and neural characteristics in adult offspring during the late middle-age period. Accumulating evidence suggests that maternal inflammation and infection during pregnancy increase risk for schizophrenia and depression in offspring, as well as for more severe outcomes among schizophrenia cases. However, no studies have determined whether difficulties persist into later periods of development, and the ability to draw inferences from existing studies has been limited by a variety of factors, such as selecting participants based on mental disorder status of offspring. Due to these limitations, previous studies have been unable to control variability in the level of exposure to inflammation within groups, control for potential confounding factors, and include outcomes that may be more directly linked to inflammation than psychiatric diagnoses. The proposed project aims to randomly select participants from a birth cohort with previously analyzed cytokine data to determine whether variability in fetal exposure to inflammation is related to specific neural and symptomatic outcomes that occur across disorders, which could provide findings pertinent to a range of neurodevelopmental sequelae. The proposed study is based on a very unique cohort, the Child Health and Development Study (CHDS), with biosamples collected during pregnancy, continual follow-up of offspring through adolescence, and assessment of a multitude of potential pre- and postnatal covariates. Specifically, 20,000 women were followed throughout their pregnancies from 1959-1966; a subset of offspring were given a range of assessments at multiple points from birth to adolescence. Previous findings from our group indicated consistent links between 2nd trimester inflammation and infection to increased risk of offspring depression, as well as childhood difficulties (e.g., internalization). The proposed project will collect detailed clinical (questionnaires, semi-structured interviews, and laboratory tasks), neurocognitive, and brain (multi- modal MRI) indices for offspring exposed to varying levels of inflammation in utero. The specific aims are as follows: to investigate whether fetal exposure to higher levels of inflammation increases risk for 1) specific symptom dimensions among offspring (e.g., psychotic symptoms, reward functioning, depression), and/or for 2) specific neurocognitive and neurological outcomes among offspring (assessed using multi-modal brain imaging and neuropsychological testing), and 3) to determine whether links between fetal exposure to inflammation and childhood/adolescent outcomes persist into middle-age. The proposed study is uniquely positioned to answer key questions about how maternal inflammation during pregnancy contributes to neurocognitive, brain, and clinical disturbances in offspring at various periods of development, has the potential to influence the development of intervention and prevention strategies, and could help clarify the role of inflammation in neurodevelopment and in a variety of mental disorders.

项目概要/摘要 这是重新提交的申请，旨在研究妊娠期间母体炎症如何发生 影响中年晚期成年后代的临床、神经认知和神经特征 时期。越来越多的证据表明，怀孕期间母体炎症和感染会增加 后代患精神分裂症和抑郁症的风险，以及精神分裂症中更严重后果的风险 案例。然而，尚无研究确定困难是否会持续到发展后期，以及 从现有研究中得出推论的能力受到多种因素的限制，例如选择 参与者基于后代的精神障碍状况。由于这些限制，之前的研究 无法控制组内炎症暴露水平的变异性，控制潜在的 混杂因素，包括可能与炎症比精神疾病更直接相关的结果 诊断。该项目旨在从出生队列中随机选择参与者 分析细胞因子数据以确定胎儿暴露于炎症的变异性是否与特定的 跨疾病发生的神经和症状结果，这可以提供与疾病相关的发现 一系列神经发育后遗症。拟议的研究基于一个非常独特的群体，即儿童 健康与发展研究（CHDS），在怀孕期间收集生物样本，持续随访 后代到青春期，并对多种潜在的产前和产后协变量进行评估。 具体而言，从 1959 年到 1966 年，对 20,000 名妇女的整个怀孕期进行了跟踪调查；后代的子集 从出生到青春期的多个阶段都接受了一系列评估。我们之前的发现 研究小组表明，妊娠中期炎症和感染与后代风险增加之间存在一致的联系 抑郁症以及童年困难（例如内化）。拟议的项目将收集详细的 临床（问卷、半结构化访谈和实验室任务）、神经认知和大脑（多学科） 模态 MRI）对子宫内暴露于不同程度炎症的后代的指数。具体目标如下 如下：调查胎儿暴露于较高水平的炎症是否会增加 1) 特定的风险 后代的症状维度（例如精神病症状、奖赏功能、抑郁），和/或 2) 后代的特定神经认知和神经学结果（使用多模式大脑评估 成像和神经心理学测试），以及 3）确定胎儿暴露于 炎症和儿童/青少年结局持续到中年。拟议的研究是独一无二的 旨在回答有关怀孕期间母体炎症如何影响的关键问题 后代在不同发育时期的神经认知、大脑和临床障碍，有可能 影响干预和预防策略的制定，并有助于阐明 神经发育和各种精神障碍中的炎症。

项目成果

From Womb to Neighborhood: A Racial Analysis of Social Determinants of Psychosis in the United States.

• DOI: 10.1176/appi.ajp.2020.20071091
• 发表时间: 2021-07
• 期刊: The American journal of psychiatry
• 作者: Anglin DM;Ereshefsky S;Klaunig MJ;Bridgwater MA;Niendam TA;Ellman LM;DeVylder J;Thayer G;Bolden K;Musket CW;Grattan RE;Lincoln SH;Schiffman J;Lipner E;Bachman P;Corcoran CM;Mota NB;van der Ven E
• 通讯作者: van der Ven E

Environmental Risk Factors and Cognitive Outcomes in Psychosis: Pre-, Perinatal, and Early Life Adversity.

• DOI: 10.1007/7854_2022_378
• 发表时间: 2023
• 期刊: Current topics in behavioral neurosciences
• 作者: Lipner, Emily;O'Brien, Kathleen J;Pike, Madeline R;Ered, Arielle;Ellman, Lauren M
• 通讯作者: Ellman, Lauren M