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: 10065446
• 负责人: Lei Wang
• 金额: $ 59.87万
• 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/10065446
• 关键词: Accounting; Address; Adolescence; Adolescent; Adult; Affect; Affective; Age; Alcohol or Other Drugs use; Anti-Retroviral Agents; Attenuated; Automobile Driving; Behavior; Behavior assessment; Behavioral; Brain; Brain region; Breast Feeding; Cessation of life; Child; Childhood; Clinical; Cognition; Cognitive; Collaborations; Communities; 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; Preventive Intervention; 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; pregnant; prenatal; prenatal exposure; protective factors; recruit; skill acquisition; skills; social structure; 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.

项目摘要 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），但 是艾滋病毒未感染的（PHEU）。最近的研究揭示了认知挑战，心理健康问题和 提高冒险行为的速度包括Pheu（YPHEU）青年的药物使用率。现存的， 横断面神经影像学研究表明YPHEU的大脑发育破坏，但基础 神经机制，特别是与产前HIV和ARV暴露有关的神经机制，尚不清楚。 支持情绪调节的网络功能障碍与儿童心理病理学有关 尽管风险行为增加了，但在青年时期的冒险行为，但我们在YPHEU方面知之甚少。我们提出了一个 纵向调查以解决我们目前的理解中这些差距。我们的中心假设是 支持情绪调节的网络中断以及与其他发育风险的互动是关键的关键 了解YPHEU心理健康，认知和行为的缺陷。我们将评估大脑网络 利用发展，心理健康，自我调节和其他认知领域以及冒险行为 190 YPHEU的功能和结构性神经影像学，临床和计算机的评估和任务 （10 - 14年）基线，两年后。参与者将从小儿艾滋病毒/艾滋病队列中招募 研究（PHAC）对艺术毒性研究（SMARTT）的监视监测。 AIM 1将利用协调 NIH资助的ABCD研究的年龄和性别匹配的神经影像学和行为数据超过10,000 每年遵循9-10岁的儿童，与大脑网络发展，认知相比 和行为，以及他们之间的关系。 AIM 2将检查类型和时机的影响 围产期ARV和其他围产期暴露，例如在大脑网络开发中使用物质 ypheu。我们还将研究可能对大脑产生独立影响的社会和结构性因素 开发或与围产期暴露相互作用。进一步我们对终身影响的理解 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 它们对过渡到成人独立的影响，在50名Pheu的年轻人中，围产期获得了50个 艾滋病毒（PHIV），年龄在22-29岁，参加了PHACS青少年大师协议（AMP UP）研究。我们将 利用统一的年龄和性别匹配的健康的年轻成人神经影像和行为数据 NIH资助了人类连接项目以比较结果。认识到重要的公共卫生 ARV暴露对YPHEU的长期认知和行为结果的影响的影响， 该项目利用多个NIH支持的多中心研究并建立了合作，将确定 驱动认知和行为结果的机制，通知急需预防的关键数据 以及全球YPHEU数量惊人的干预策略。