TERBO BRAIN Study: Trajectories of Emotional Regulation and Behavior Outcomes and related Brain Regions And Intrinsic Networks

TERBO BRAIN 研究：情绪调节和行为结果的轨迹以及相关的大脑区域和内在网络

• 批准号: 10264955
• 负责人: Lei Wang
• 金额: $ 43.03万
• 依托单位: HARVARD SCHOOL OF PUBLIC HEALTH
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-18 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10264955
• 关键词: Accounting; Address; Adolescence; Adolescent; Adult; Affect; Affective; Age; Anti-Retroviral Agents; Attenuated; Automobile Driving; Behavior; Behavior assessment; Behavioral; Brain; Brain region; Breast Feeding; Cessation of life; Child; Childhood; Clinical; Cognition; Cognitive; Collaborations; Computers; Data; Development; Discrimination; Disease; Education; Emotional; Emotions; Enrollment; Exhibits; Exposure to; Family; Funding; Gender; General Population; Growth; HIV; HIV Infections; HIV antiretroviral; HIV/STD; Health; Homelessness; Human; Impaired cognition; Impairment; Imprisonment; Infection; Informal Social Control; Intervention; Investigation; Language; Life; Light; Link; Measures; Mediating; Mediation; Mental Health; Mental disorders; Modeling; Monitor; Multicenter Studies; Neurocognitive; Outcome; Participant; Pediatric HIV/AIDS Cohort Study; Perinatal; Perinatal Exposure; Personal Satisfaction; Pharmaceutical Preparations; Population; Protocols documentation; Psychopathology; Public Health; Regulation; Research; Rewards; Risk; Risk Behaviors; Risk-Taking; Safety; Sampling; Structure; Time; Toxic effect; United States National Institutes of Health; Unsafe Sex; Violence; Vocation; Woman; Youth; adolescent substance use; antiretroviral therapy; attenuation; base; behavioral outcome; brain abnormalities; cognitive function; cohort; congenital anomaly; connectome; early childhood; efavirenz; emotion regulation; emotional behavior; experience; improved; in utero; large scale data; network dysfunction; neurodevelopment; neuroimaging; neuromechanism; neurotoxic; pediatric human immunodeficiency virus infection; perinatal HIV; poor communities; pregnant; prenatal; prenatal exposure; preventive intervention; protective factors; recruit; skill acquisition; skills; social structure; substance use; success; support network; surveillance study; young adult

PROJECT SUMMARY An estimated 15 million children worldwide are living with perinatal HIV and antiretroviral (ARV) exposure, but are HIV-uninfected (PHEU). Recent studies reveal cognitive challenges, mental health problems, and increased rates of risk-taking behaviors including substance use among youth with PHEU (YPHEU). Existing, cross-sectional neuroimaging studies indicate disrupted brain development among YPHEU, yet the underlying neural mechanisms, particularly related to prenatal HIV and ARV exposure, are not well understood. Dysfunction of networks supporting emotional regulation has been linked with childhood psychopathologies and risk-taking behavior in youth, yet we know little in YPHEU despite increased risk behaviors. We propose a longitudinal investigation to address these gaps in our current understanding. Our central hypothesis is that disruption of networks supporting emotion regulation, and interaction with other developmental risks, are key to understanding deficits in mental health, cognition and behavior in YPHEU. We will assess brain network development, mental health, self-regulation and other cognitive domains, and risk-taking behavior, utilizing functional and structural neuroimaging, clinical and computer-based assessments and tasks, in 190 YPHEU (10-14 years) at baseline, and 2 years later. Participants will be recruited from the Pediatric HIV/AIDS Cohort Study (PHACS) Surveillance Monitoring of ART Toxicity Study (SMARTT). Aim 1 will leverage harmonized age- and gender-matched neuroimaging and behavioral data from the NIH funded ABCD study on over 10,000 children age 9-10 years followed yearly, to compare with trajectories of brain network development, cognition and behavior, as well as their relationships among YPHEU. Aim 2 will examine the impact of type and timing of perinatal ARVs and other perinatal exposures such as substance use on brain network development within YPHEU. We will also examine social and structural factors that may have independent effects on brain development or interact with perinatal exposures. To further our understanding of lifetime implications of perinatal exposures, exploratory Aim 3 will explore long-term brain network and behavioral consequences, and their effect on transition to adult independence, in 50 young adults with PHEU and 50 with perinatally acquired HIV (PHIV), age 22-29, enrolled in the PHACS Adolescent Master Protocol-Up (AMP Up) study. We will leverage harmonized age- and gender-matched healthy young adult neuroimaging and behavioral data from the NIH funded Human Connectome Project to compare outcomes. Recognizing significant public health implications of the effects of ARV exposure on long-term cognitive and behavioral outcomes among YPHEU, this project, leveraging multiple NIH-supported multicenter studies and established collaborations, will identify mechanisms driving cognitive and behavioral outcomes, critical data for informing much needed prevention and intervention strategies for the staggering numbers of YPHEU globally.

项目概要 据估计，全世界有 1500 万儿童患有围产期艾滋病毒和抗逆转录病毒 (ARV) 暴露，但是 未感染 HIV（PHEU）。最近的研究揭示了认知挑战、心理健康问题和 患有 PHEU (YPHEU) 的青少年中，包括药物使用在内的冒险行为发生率增加。现存的， 横断面神经影像研究表明 YPHEU 的大脑发育受到干扰，但潜在的原因 神经机制，特别是与产前艾滋病毒和抗逆转录病毒暴露相关的神经机制，尚不清楚。 支持情绪调节的网络功能障碍与儿童精神病理学有关 尽管危险行为有所增加，但我们对 YPHEU 知之甚少。我们提出一个 纵向调查以解决我们当前理解中的这些差距。我们的中心假设是 支持情绪调节的网络的破坏以及与其他发育风险的相互作用是关键 了解 YPHEU 的心理健康、认知和行为缺陷。我们将评估大脑网络 发展、心理健康、自我调节和其他认知领域以及冒险行为，利用 功能和结构神经影像、临床和基于计算机的评估和任务，190 YPHEU 基线时（10-14 岁）和 2 年后。参与者将从儿科艾滋病毒/艾滋病队列中招募 研究 (PHACS) ART 毒性研究 (SMARTT) 监测。目标 1 将利用协调一致的杠杆 来自 NIH 资助的 ABCD 研究的年龄和性别匹配的神经影像和行为数据，涉及超过 10,000 人 每年对 9-10 岁儿童进行随访，以比较大脑网络发育、认知的轨迹 和行为，以及他们与 YPHEU 之间的关系。目标 2 将检查类型和时间安排的影响 围产期抗逆转录病毒药物和其他围产期暴露，例如药物使用对大脑网络发育的影响 YPHEU。我们还将研究可能对大脑产生独立影响的社会和结构因素 发育或与围产期暴露相互作用。为了进一步加深我们对终生影响的理解 围产期暴露，探索性目标 3 将探索长期的大脑网络和行为后果，以及 它们对 50 名患有 PHEU 的年轻人和 50 名患有围产期获得性遗传病的年轻人向成人独立过渡的影响 HIV (PHIV)，年龄 22-29 岁，参加 PHACS 青少年主协议升级 (AMP Up) 研究。我们将 利用统一的年龄和性别匹配的健康年轻成人神经影像和行为数据 美国国立卫生研究院 (NIH) 资助了人类连接组项目来比较结果。认识到重要的公共卫生 抗逆转录病毒药物暴露对 YPHEU 的长期认知和行为结果的影响的影响， 该项目利用 NIH 支持的多项多中心研究和已建立的合作，将确定 驱动认知和行为结果的机制，为急需的预防提供信息的关键数据 针对全球数量惊人的 YPHEU 的干预策略。