Implications of cannabis use and cumulative adversity exposure for brain structure and function in young adults living with HIV.

大麻使用和累积逆境暴露对艾滋病毒感染者的大脑结构和功能的影响。

• 批准号: 10394895
• 负责人: CHRISTINE FENNEMA-NOTESTINE
• 金额: $ 69.81万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-15 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10394895
• 关键词: Affect; Age; Anti-Inflammatory Agents; Area; Attenuated; Behavior; Behavioral; Biological Markers; Brain; Cannabis; Chronic; Cognition; Cognitive; Corpus striatum structure; Data; Detection; Diffusion; Early Diagnosis; Emotional; Enrollment; Exposure to; Face; Frequencies; HIV; HIV Infections; Health; Hippocampus (Brain); Image; Immune; Immunologic Markers; Immunosuppression; Individual; Infection; Inflammation; Inflammatory; Institution; Intervention; Lead; Light; Link; Magnetic Resonance Imaging; Magnetoencephalography; Measures; Mediating; Mediation; Mediator of activation protein; Memory; Metabolism; Methods; Modeling; Nervous System Physiology; Nervous system structure; Neuraxis; Neurites; Neurocognitive; Neurocognitive Deficit; Neurologic; Outcome; Pathogenesis; Pathway interactions; Performance; Plasma; Post-Traumatic Stress Disorders; Prefrontal Cortex; Prevention; Research; Rest; Risk; Short-Term Memory; Stress; Structure; System; Techniques; Verbal Learning; Violence; Virus Latency; Work; Youth; advanced analytics; aged; antiretroviral therapy; comorbidity; density; emotion regulation; executive function; experience; high risk; immune activation; immune function; improved; innovation; maltreatment; marijuana use; multimodality; neurodevelopment; neuroimaging; neuroinflammation; novel; peer; stress disorder; substance use; temporal measurement; traumatic event; white matter; young adult

Antiretroviral therapy (ART) has lessened but not eliminated the central nervous system (CNS) impact of human immunodeficiency virus (HIV). With effects on cognition and brain integrity now subtler, yet chronic with unknown long-term implications, the potential of comorbid conditions to moderate, obscure or ameliorate HIV effects is increasingly important. Young adults (“youth”) have high rates of both new HIV infection and understudied common comorbidities with significant potential to influence HIV’s CNS presentation: cannabis use and cumulative adversity. Both may alter immune functioning and inflammation as pathways for their influence on HIV’s CNS effects, in addition to their independent impact. Our preliminary data show that worse cognitive and neuroimaging outcomes in youth with HIV (YWH) compared to controls (e.g., worse memory and executive functioning, thinner prefrontal cortex, altered functional activation using magnetoencephalography [MEG]) are attenuated or, in some cases, reversed by light to moderate, but not heavy, cannabis use. We hypothesize that worse cognitive and neuroimaging outcomes in treated YWH, compared to controls, in the context of no cannabis use will be ameliorated by mild to moderate cannabis use, while high cannabis use frequency will be associated with worse outcomes in both groups. Of importance, fully understanding the interplay of HIV and cannabis may require consideration of lifetime experiences of adversity. Strong evidence shows that exposure to adverse circumstances, such as maltreatment, violence, and stress, can alter immune and CNS systems, and such exposure is common among YWH and comparable seronegative risk groups. We will assess the influence of cumulative adversity in mediating effects of cannabis and HIV. The proposed study will determine the interactive effects of HIV, cannabis and cumulative adversity on CNS structure and function in 75 YWH (age 18-24) and 75 comparable controls. We will use innovative neuroimaging approaches (MEG to measure functional activity and advanced diffusion approaches), along with brain structure and metabolism and neurocognitive assessment. We will examine mediation of HIV, cannabis and cumulative adversity interactions by inflammation and immune activation, assessed using plasma biomarkers. Examining the interplay of these influences on CNS function and structure will be facilitated by careful characterization of substance use, assessment of cumulative adversity burden rather than single traumatic events, and advanced statistical techniques. Thus, we will examine interactive HIV and cannabis effects on key brain systems; model underlying mechanisms; and examine an important yet understudied influence, cumulative adversity. The study has potential for high impact by improving detection of HIV’s CNS effects and our understanding of pathogenesis. It would enable better prevention of CNS decline, institution of CNS-targeted treatments and cure strategies, and in general mitigation of the CNS impact of HIV for individuals who are early in infection and still in the midst of neurodevelopment where early detection may have the greatest benefit.

抗逆转录病毒疗法（ART）减少了，但没有消除中枢神经系统（CNS）的影响 人类免疫缺陷病毒（HIV）。现在对认知和大脑完整性的影响现在细致 未知的长期含义，合并症条件对中度，晦涩或改善HIV的潜力 影响越来越重要。年轻人（“青年”）的新艾滋病毒感染和 研究的常见合并症具有影响艾滋病毒中枢神经系统介绍的巨大潜力：大麻 使用和累积广告。两者都可能改变免疫功能和炎症作为其途径 除了独立影响外，还对艾滋病毒的中枢神经系统效应的影响。我们的初步数据表明更糟 与对照组相比 执行功能，较薄的前额叶皮层，使用磁脑摄影改变功能激活 [MEG]）被衰减，或者在某些情况下会被光线逆转到中度但不重要的大麻使用。我们 假设与对照组相比 轻度至中度大麻的使用，不使用大麻的上下文将得到改善，而大麻使用高 两组的频率将与差的结果相关。重要性，完全理解 艾滋病毒和大麻的相互作用可能需要考虑一生的广告经验。有力的证据 表明暴露于虐待，暴力和压力等不利情况可以改变免疫力 和中枢神经系统系统以及这种暴露在YWH和可比的血清质风险组中很常见。我们 将评估累积广告对大麻和艾滋病毒的中介作用的影响。拟议的研究 将确定艾滋病毒，大麻和累积广告对中枢神经系统结构和功能的互动影响 在75 YWH（18-24岁）和75个可比较的对照中。我们将使用创新的神经影像学方法（MEG至 测量功能活性和晚期扩散方法），以及大脑结构和代谢 和神经认知评估。我们将研究艾滋病毒，大麻和累积广告的调解 使用血浆生物标志物评估，通过炎症和免疫激活进行相互作用。检查 这些影响对中枢神经系统功能和结构的相互作用将通过仔细表征来制备 药物使用，评估累积冒险燃烧而不是单个创伤事件，并先进 统计技术。这是我们将检查对关键大脑系统的互动HIV和大麻的影响。模型 基本机制；并检查一个重要但知识的影响，累积广告。 研究通过改善艾滋病毒中枢神经系统效应的检测以及我们对 发病。它将能够更好地预防中枢神经系统下降，针对中枢神经系统的治疗机构 治愈策略，并普遍缓解艾滋病毒对感染早期个人的中枢神经系统影响 并且仍处于神经发育中，那里的早期检测可能会带来最大的好处。