Scrutinizing neuro-immune regulatory mechanisms underlying depressive symptomatology in young adults with HIV

仔细检查年轻艾滋病毒感染者抑郁症状背后的神经免疫调节机制

• 批准号: 10370250
• 负责人: Suzi Hong
• 金额: $ 19.75万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-10 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10370250
• 关键词: Adherence; Adrenal Glands; Adrenergic Receptor; Affect; Affective; Agonist; Anhedonia; Anisotropy; Anterior; Behavioral; Biological; Blood; Brain; Brain region; CD4 Positive T Lymphocytes; Caregivers; Cell Count; Cell model; Cell physiology; Choline; Clinical; Cognitive; Coupled; Data; Demographic Factors; Diffusion Magnetic Resonance Imaging; Etiology; Exploratory/Developmental Grant; Functional disorder; Future; Glucocorticoid Receptor; Glucocorticoids; HIV; HIV Infections; Health; Healthcare; High Prevalence; Immune; Individual; Inflammation; Inflammatory; Inositol; Investigation; Knowledge; Lead; Magnetic Resonance Spectroscopy; Major Depressive Disorder; Measures; Mediating; Mediator of activation protein; Mental Depression; Modality; Modeling; Mood Disorders; Moods; Morbidity - disease rate; Neurobiology; Neuroimmune; Neurons; Neurosecretory Systems; Participant; Pathway interactions; Plasma; Population; Quality of life; Regulation; Reporting; Research; Role; Structure; Symptoms; Time; Viral; Viral Load result; Youth; aged; brain pathway; clinically relevant; depressive symptoms; imaging biomarker; immune function; inflammatory marker; insight; marijuana use; monocyte; mortality; multimodality; neuroimaging; neuroimaging marker; neuroinflammation; peripheral blood; psychologic; psychosocial; receptor; response; sociodemographics; symptomatology; targeted treatment; therapeutic target; treatment adherence; white matter; young adult; Adherence; Adrenal Glands; Adrenergic Receptor; Affect; Affective; Agonist; Anhedonia; Anisotropy; Anterior; Behavioral; Biological; Blood; Brain; Brain region; CD4 Positive T Lymphocytes; Caregivers; Cell Count; Cell model; Cell physiology; Choline; Clinical; Cognitive; Coupled; Data; Demographic Factors; Diffusion Magnetic Resonance Imaging; Etiology; Exploratory/Developmental Grant; Functional disorder; Future; Glucocorticoid Receptor; Glucocorticoids; HIV; HIV Infections; Health; Healthcare; High Prevalence; Immune; Individual; Inflammation; Inflammatory; Inositol; Investigation; Knowledge; Lead; Magnetic Resonance Spectroscopy; Major Depressive Disorder; Measures; Mediating; Mediator of activation protein; Mental Depression; Modality; Modeling; Mood Disorders; Moods; Morbidity - disease rate; Neurobiology; Neuroimmune; Neurons; Neurosecretory Systems; Participant; Pathway interactions; Plasma; Population; Quality of life; Regulation; Reporting; Research; Role; Structure; Symptoms; Time; Viral; Viral Load result; Youth; aged; brain pathway; clinically relevant; depressive symptoms; imaging biomarker; immune function; inflammatory marker; insight; marijuana use; monocyte; mortality; multimodality; neuroimaging; neuroimaging marker; neuroinflammation; peripheral blood; psychologic; psychosocial; receptor; response; sociodemographics; symptomatology; targeted treatment; therapeutic target; treatment adherence; white matter; young adult

Project Summary/Abstract Mood disorders are prevalent among individuals living with HIV for which multi-dimensional, contributing factors exist. Especially, 20-50% of youth living with HIV (YWH) report depression or elevated depressive symptoms of clinical relevance. Depression or elevated depressive symptoms in YWH result in HIV include poor adherence to HIV treatment, poor viral suppression, increased morbidity and mortality as well as decreased quality of life. In spite of growing data showing the association between blood inflammatory markers and levels of depressive mood or clinical depression in HIV- and HIV+ individuals, inconsistent findings across the studies in the inflammatory marker-depression associations pose challenges in understanding mechanisms and lead to a paucity of targeted therapeutics. Given the profound modulatory effects of multiple branches of the neuroendocrine system on immune/inflammatory activities, we propose to conduct simultaneous investigations of potentially concurrent but disparate neuro-immune pathways (“NIP”) of inflammation dysregulation (IR) in predicting depressive symptoms in 45 YWH and 45 Control youth (aged 18-25 yrs), by leveraging an ongoing R01 study of brain function and cannabis use in YWH (DA047906). We will employ an ex vivo cellular model of peripheral blood monocytes by which effects of various receptor agonists in cellular IR will be assessed [1) sympatho-adrenal (SA)/adrenergic receptor (AR); 2) glucocorticoid (GC)/GC receptor (GR), and 3) dopaminergic (DA)/DR pathways] in predicting depressive symptoms (Aim 1). The neuroimaging markers of neuroinflammation from R01 [1) diffusion tensor imaging measures (e.g., fractional anisotropy), 2) structural alterations (i.e., white matter abnormality), and 3) metabolites through MR Spectroscopy (i.e., higher choline and myo-inositol, indicating diminished neuronal integrity and increased inflammation)] will be examined as a mediator (Aim 2). We will also explore differing depressive symptom domains [1) cognitive, 2) affective, and 3) somatic domains as well as 4) apathy and 5) anhedonia], as initial evidence shows symptoms specific to HIV infection such as somatic symptoms and apathy which may provide insight into delineating NIP- brain regions-symptoms network (Aim 3). Many types of the data collected in the R01 study will be shared with this R21 such as sociodemographic; clinical; psychological and behavioral; and neuroimaging data, maximizing the feasibility of this R21. Our simultaneous investigation of three NIP pathways with careful analytical plans in predicting depressive symptoms will provide an opportunity to gain mechanistic knowledge beyond plasma inflammatory marker-depression associations and to inform targeted therapeutic modalities.

项目摘要/摘要 情绪障碍在艾滋病毒的患者中普遍存在，多维的人有贡献 存在因素。特别是20-50％的艾滋病毒（YWH）年轻人报告抑郁症或抑郁症 临床相关性的症状。抑郁症或YWH中的抑郁症状升高导致HIV包括 对艾滋病毒治疗的依从性不佳，病毒抑制不良，发病率和死亡率增加以及 生活质量下降。尽管数据增长，但显示了血液炎症标记之间的关联 艾滋病毒和艾滋病毒+个体的抑郁情绪或临床抑郁水平，各种发现不一致 炎症标志性抑郁症关联的研究在理解机制方面构成了挑战 并导致靶向疗法很少。考虑到多个分支的深刻调节作用 关于免疫/炎症活动的神经内分泌系统，我们建议同时进行 对炎症的潜在并发神经免疫途径（“ nip”）的研究 在预测45 YWH和45名对照青年（18-25岁）的抑郁症状方面的失调（IR）， 利用YWH中正在进行的R01大脑功能和大麻使用研究（DA047906）。我们将采用一个 外周血单核细胞的体内细胞模型，通过这些模型，各种受体激动剂在细胞IR中的作用 将评估[1）交感神经（SA）/肾上腺素受体（AR）； 2）糖皮质激素（GC）/GC受体 （GR）和3）多巴胺能（DA）/DR途径]在预测抑郁症状（AIM 1）中。神经影像 从R01 [1）扩散张量成像指标（例如分数各向异性）的神经炎症的标记物，2） 结构改变（即白质异常）和3）通过MR光谱法代谢（即， 胆碱和肌醇，表明神经元完整性降低，影响的增加） 被检查为调解人（AIM 2）。我们还将探索区分抑郁症状领域[1）认知，2） 情感和3）躯体结构域以及4）冷漠和5）Anhedonia]，因为初始证据表明症状 特定于艾滋病毒感染的特定于躯体符号和冷漠，这些符号可能会洞悉描述nip- 脑部区域肿瘤网络（AIM 3）。 R01研究中收集的许多类型的数据将与 这种R21，例如社会人口统计学；临床;心理和行为；和神经影像学数据，最大化 此R21的可行性。我们对三个NIP途径的简单投资，并仔细的分析计划 预测抑郁症状将为获得血浆以外的机械知识提供机会 炎症标记 - 抑郁症的关联并告知有针对性的治疗方式。