Impact of Cannabinoid Use on HIV-related Brain Alterations in Young Adults

大麻素的使用对年轻人与艾滋病毒相关的大脑变化的影响

基本信息

批准号：
8914796
负责人：
CHRISTINE FENNEMA-NOTESTINE
金额：
$ 19.38万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-05-01 至 2017-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8914796
关键词：
Accounting Adolescence Adolescent Adolescent and Young Adult Adult Affect Age Alcohol or Other Drugs use Anti-Inflammatory Agents Anti-inflammatory Attenuated Automobile Driving Behavior assessment Biological Markers Brain CD4 Lymphocyte Count Cannabinoids Cannabis Choline Clinical Cognition Cognitive Comorbidity Complex Development Diffusion Magnetic Resonance Imaging Disease Progression Effectiveness Encephalitis Etiology Evolution Future HIV Health Immune Immunosuppression Immunosuppressive Agents Impaired cognition Individual Infection Inflammation Inflammatory Inflammatory Response Inositol Interleukin-6 Intervention Investigation Learning Life Light Link Literature Macrophage Activation Magnetic Resonance Imaging Marijuana Measures Mediator of activation protein Memory Monitor Motor Neuraxis Neurocognitive Neurologic Neurons Neuropathogenesis Outcome Participant Pathogenesis Pathway interactions Performance Pilot Projects Plasma Population Predisposition Property Recording of previous events Relative (related person)Research Risk Role Short-Term Memory Staging Substance of Abuse Time Toxic effect Tumor Necrosis Factor-alpha Virus Diseases Work Youth aged antiretroviral therapy chemokine cognitive function cognitive testing cohort cytokine executive function gray matter immune function improved inflammatory marker innovation insight interdisciplinary approach male marijuana use memory process monocyte nervous system development neurodevelopment neuroimaging peer processing speed public health relevance relating to nervous system spectroscopic imaging success theories white matter white matter damage young adult

项目摘要

DESCRIPTION (provided by applicant): The purpose of the proposed research is to develop a multimodal approach to elucidate the combined effects of HIV infection and cannabis use on the brain in youth. An increasing proportion of new human immunodeficiency virus (HIV) infections occur in adolescents and young adults, or youth, living with HIV (YLWH; 25-30% in 2010). YLWH are in the midst of completing CNS development and will live with HIV infection and associated treatment for a long time. Evidence from adults suggests continuing CNS effects of HIV infection despite antiretroviral therapy; however, we know little about the impact of HIV infection and its treatments on the CNS in YLWH. Recent findings suggest significant cognitive impairments in behaviorally- infected YLWH, although the causal factors are unknown and likely multifactorial. Current theories of HIV- associated neuropathogenesis focus on the role of systemic and neural inflammation, although existing findings come largely from studies of adults with complex comorbidities and treatment histories. A better understanding of CNS changes in behaviorally-infected YLWH, then, will provide important insight and may have clinical implications regarding CNS pathogenesis. Of importance, this cohort is characterized by a high rate of cannabis use, which may impact the progression of HIV infection and associated cognitive and neurological alterations. Cannabinoids have been linked to greater immune suppression and increased vulnerability to infection; however, they also may alter cytokine and chemokine expression, driving an anti- inflammatory response. The literature suggests a potential increase in susceptibility to more rapid disease progression alongside parallel anti-inflammatory effects. Cannabis use in adolescence has been linked independently to changes in neuroimaging and cognitive functioning. The possibility of complex interplay among the CNS effects of HIV infection and cannabis use requires further investigation for guidance on the development of relevant treatment interventions in youth. The proposed study aims to explore the impact of cannabis use on HIV-associated CNS effects by studying YLWH (age 18-24) and control participants using an interdisciplinary approach that will include multimodal neuroimaging measures, plasma biomarkers of inflammation and immune function, and neurocognitive outcomes. This pilot project will initiate an essential characterization of the CNS effects of behaviorally-acquired HIV infection in YLWH; explore the impact of comorbid cannabis use; initiate the critical assessment of inflammation as a mediator of observed effects; and explore promising combinations of neuroimaging, plasma biomarker, and clinical variables for future studies. The resultant findings will set the stage for multisite, multi-disciplinary investigations by characterizing the neurologic and inflammatory signatures of HIV and comorbid cannabis use in youth and suggesting functionally meaningful biomarkers for identifying individuals at risk for CNS decline, monitoring effectiveness and toxicity associated with ART, and exploring interactions with other common substances of abuse.

描述（由适用提供）：拟议的研究的目的是开发一种多模式的方法来阐明年轻人对大脑的艾滋病毒感染和大麻使用对大脑的综合作用。越来越多的新人免疫缺陷病毒（HIV）感染发生在青少年和年轻人或年轻人中，患有艾滋病毒的年轻人（YLWH； 2010年25-30％）。 YLWH正在完成CNS开发中，并将长期接受HIV感染和相关治疗。成人的证据表明，艾滋病毒感染目的地抗逆转录病毒疗法的继续影响。但是，我们对HIV感染及其治疗对CNS的影响一无所知。最近的发现表明，尽管因果因素是未知的，并且可能多因素多因素，但行为感染的YLWH的认知障碍很大。尽管现有发现很大程度上来自对具有复杂合并症和治疗史的成年人的研究，但与HIV相关的神经病发生的当前理论集中在系统性和神经炎症的作用上。那么，对行为感染的YLWH的中枢神经系统变化有更好的了解将提供重要的见解，并可能对CNS发病机理具有临床意义。重要的是，该队列的特征是大麻使用率很高，这可能会影响HIV感染以及相关的认知和神经系统改变的进展。大麻素与更大的免疫抑制和增加感染的脆弱性有关。但是，它们也可能改变细胞因子和趋化因子的表达，推动抗炎反应。文献表明，与平行的抗炎作用以及平行的抗炎作用相比，对更快疾病进展的敏感性有可能提高。在青少年中使用大麻已与神经影像学和认知功能的变化独立联系。艾滋病毒感染和大麻使用的中枢神经系统效应之间需要进行复杂的相互作用的可能性需要进一步投资，以指导年轻人的相关治疗干预措施。拟议的研究旨在通过研究YLWH（18-24岁）和使用跨学科方法来探索大麻使用对HIV相关的CNS效应的影响，该方法将包括多模式神经成像措施，炎症和免疫功能以及神经认知能力的血浆生物标志物，以及神经认知能力的胜利。该试点项目将启动对YLWH行为可获得的HIV感染的CNS影响的基本表征。探索合并大麻使用的影响；启动对感染的关键评估，作为观察效应的介体；并探索神经影像学，血浆生物标志物和临床变量的有希望的组合，以供将来研究。随之而来的发现将通过表征年轻人中HIV和合并症大麻使用的神经系统和炎症性特征，并提出有意义的生物标志物来识别有意义的生物标志物，以识别有意义的生物标志物，以识别CNS下降的风险，监测与其他常见滥用的艺术相互作用以及与其他常见的滥用相关性相关性，并提出有意义的生物标志物，并提出有意义的生物标志物，并提出有意义的生物标志物，并提出有意义的生物标志物，并提出有意义的生物标志物，并提出有意义的生物标志物，并提出有意义的生物标志物。