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

项目总结 据估计，全球有1500万儿童感染了围产期艾滋病毒和抗逆转录病毒(ARV)，但 是未感染艾滋病毒(PHEU)的人。最近的研究表明，认知挑战、心理健康问题以及 Pheu(YPHEU)青年中包括药物使用在内的冒险行为的比率增加。现有的， 横断面神经成像研究表明，YPHEU患者的大脑发育受到干扰，但潜在的 神经机制，特别是与产前HIV和ARV接触有关的机制，还没有被很好地理解。 支持情绪调节的网络功能障碍与儿童精神病态有关 和年轻人的冒险行为，但我们对YPHEU知之甚少，尽管危险行为增加。我们提出了一个 进行纵向调查，以解决我们目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中断，以及与其他发育风险的相互作用，是 了解青少年儿童心理健康、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 190YPHEU的功能和结构神经成像、临床和基于计算机的评估和任务 (10-14岁)基线，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毒性研究的监督监测(SMART)。目标1将利用协调 来自NIH资助的ABCD研究的年龄和性别匹配的神经成像和行为数据，研究对象超过10,000人 每年跟踪观察9-10岁儿童的大脑网络发育轨迹、认知轨迹 和行为，以及它们之间的关系。目标2将检查类型和时机的影响 围产期抗逆转录病毒药物和其他围产期暴露，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有独立影响的社会和结构性因素。 发生或与围产期暴露相互作用。为了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名围产期获得者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UP(AMP UP)研究。我们会 利用协调的年龄和性别匹配的健康青年神经成像和行为数据， 美国国立卫生研究院资助了人类连接体项目，以比较结果。认识到重大的公共卫生 抗逆转录病毒药物暴露对YPHEU长期认知和行为结果的影响， 该项目利用NIH支持的多个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，提供急需的预防措施的关键数据 以及针对全球惊人数量的YPHEU的干预策略。

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.