Scrutinizing neuro-immune regulatory mechanisms underlying depressive symptomatology in young adults with HIV
Scrutinizing neuro-immune regulatory mechanisms underlying depressive symptomatology in young adults with HIV
批准号:
10370250
负责人:
Suzi Hong
金额:
$19.75万
依托单位国家:
美国
项目类别:
财政年份:
2021
资助国家:
美国
项目状态:
已结题
起止时间:
2021-09-10 至 2023-08-31
关键词:
AdherenceAdrenal GlandsAdrenergic ReceptorAffectAffectiveAgonistAnhedoniaAnisotropyAnteriorBehavioralBiologicalBloodBrainBrain regionCD4 Positive T LymphocytesCaregiversCell CountCell modelCell physiologyCholineClinicalCognitiveCoupledDataDemographic FactorsDiffusion Magnetic Resonance ImagingEtiologyExploratory/Developmental GrantFunctional disorderFutureGlucocorticoid ReceptorGlucocorticoidsHIVHIV InfectionsHealthHealthcareHigh PrevalenceImmuneIndividualInflammationInflammatoryInositolInvestigationKnowledgeLeadMagnetic Resonance SpectroscopyMajor Depressive DisorderMeasuresMediatingMediator of activation proteinMental DepressionModalityModelingMood DisordersMoodsMorbidity - disease rateNeurobiologyNeuroimmuneNeuronsNeurosecretory SystemsParticipantPathway interactionsPlasmaPopulationQuality of lifeRegulationReportingResearchRoleStructureSymptomsTimeViralViral Load resultYouthagedbrain pathwayclinically relevantdepressive symptomsimaging biomarkerimmune functioninflammatory markerinsightmarijuana usemonocytemortalitymultimodalityneuroimagingneuroimaging markerneuroinflammationperipheral bloodpsychologicpsychosocialreceptorresponsesociodemographicssymptomatologytargeted treatmenttherapeutic targettreatment adherencewhite matteryoung adult
中文摘要
项目摘要/摘要
情绪障碍在艾滋病毒携带者中普遍存在,这是多方面的,起作用的
因素是存在的。特别是,20%-50%的艾滋病毒携带者(YWH)报告抑郁或抑郁加剧
临床相关症状。基督教青年会导致HIV的抑郁或抑郁症状增加包括
艾滋病毒治疗依从性差、病毒抑制差、发病率和死亡率增加以及
生活质量下降。尽管越来越多的数据显示血液炎症标志物之间的关联
以及HIV携带者和HIV+者的抑郁情绪或临床抑郁水平,不一致的发现
炎症标记物-抑郁相关性的研究对理解机制提出了挑战
并导致靶向治疗药物的缺乏。鉴于多个分支的深刻调节作用,
神经内分泌系统对免疫/炎症活动的影响,我们建议同时进行
潜在并发但不同的炎症神经免疫通路(NIP)的研究
在45岁青年和45名对照青年(年龄在18-25岁)中预测抑郁症状的调节障碍
利用正在进行的关于YWH大脑功能和大麻使用情况的R01研究(DA047906)。我们将聘请一名
不同受体激动剂对细胞IR影响的外周血单核细胞体外模型
将评估[1)交感-肾上腺(SA)/肾上腺素能受体(AR);2)糖皮质激素(GC)/GC受体
(3)多巴胺能(DA)/DR通路]预测抑郁症状(目标1)。神经成像
R01的神经炎症标志物[1]扩散张量成像测量(例如,分数各向异性),2)
结构改变(即白质异常),以及3)磁共振波谱的代谢物(即较高的
胆碱和肌醇,表明神经元完整性降低和炎症增加)]
作为调解人接受审查(目标2)。我们还将探索不同的抑郁症状领域[1)认知,2)
情绪性,3)躯体领域,以及冷漠和快感缺乏],因为最初的证据显示症状
HIV感染的特异性,如躯体症状和冷漠,可能提供对描绘NIP的洞察力
脑区-症状网络(目标3)。在R01研究中收集的许多类型的数据将与
这一R21,如社会人口学;临床;心理和行为;以及神经成像数据,最大化
这款R21的可行性。我们同时对NIP的三条途径进行了研究,并制定了仔细的分析计划
预测抑郁症状将提供一个获得血浆以外的机制知识的机会
炎症标记物-抑郁的关联,并提供有针对性的治疗方式。
英文摘要
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.
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会议论文
Scrutinizing neuro-immune regulatory mechanisms underlying depressive symptomatology in young adults with HIV
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批准号:10487540
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项目类别:
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资助金额:$23.7万
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财政年份:2021
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依托单位:
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资助金额:$15.75万
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批准号:10209488
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资助金额:$15.75万
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财政年份:2019
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依托单位:
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批准号:9752661
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资助金额:$70.05万
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财政年份:2015
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依托单位:
Autonomic and Immuno-vascular Mechanisms of Antihypertensive Effects of Taichi
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批准号:8961203
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资助金额:$74.59万
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财政年份:2015
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依托单位:
Autonomic and Immuno-vascular Mechanisms of Antihypertensive Effects of Taichi
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批准号:9273603
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资助金额:$71.98万
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财政年份:2015
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依托单位:
Role of obesity on vascular inflammation and immune cell activation in prehyperte
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批准号:8011511
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项目类别:
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资助金额:$38.63万
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财政年份:2009
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负责人:Suzi Hong
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依托单位:
Role of obesity on vascular inflammation and immune cell activation in prehyperte
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批准号:7590157
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项目类别:
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资助金额:$38.63万
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财政年份:2009
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负责人:Suzi Hong
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依托单位:
Obesity, vascular inflammation, and immune cell activation in prehypertension
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批准号:8440356
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项目类别:
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资助金额:$36.4万
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财政年份:2009
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负责人:Suzi Hong
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依托单位:
Role of obesity on vascular inflammation and immune cell activation in prehyperte
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批准号:7839449
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项目类别:
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资助金额:$28.95万
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财政年份:2009
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负责人:Suzi Hong
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依托单位:
Obesity, vascular inflammation, and immune cell activation in prehypertension
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批准号:8209217
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项目类别:
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资助金额:$38.24万
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财政年份:2009
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负责人:Suzi Hong
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依托单位:
Role of obesity on vascular inflammation and immune cell activation in prehyperte
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批准号:7759170
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项目类别:
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资助金额:$38.63万
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财政年份:2009
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负责人:Suzi Hong
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依托单位:
海外基金