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
项目概要/摘要
情绪障碍在艾滋病毒感染者中普遍存在,
因素存在。特别是,20-50%的青年艾滋病毒感染者(YWH)报告抑郁症或抑郁程度升高,
临床相关症状。抑郁或抑郁症状加重导致艾滋病毒感染的YWH包括
艾滋病毒治疗坚持性差,病毒抑制效果差,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
以及HIV-和HIV+个体的抑郁情绪或临床抑郁水平,
炎症标志物与抑郁症相关性的研究对理解其机制提出了挑战
并导致靶向治疗药物的缺乏。考虑到神经系统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
炎症的潜在并发但不同的神经免疫途径(“NIP”)的研究
在45名YWH和45名对照青年(年龄18-25岁)中预测抑郁症状的调节障碍(IR),
利用正在进行的R 01研究YWH的脑功能和大麻使用(DA 047906)。我们将雇用一名
外周血单核细胞的离体细胞模型,通过该模型,各种受体激动剂在细胞IR中的作用
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
(GR)和3)多巴胺(DA)/DR通路]预测抑郁症状(目的1)。神经成像
来自R 01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,白色物质异常),和3)通过MR光谱的代谢物(即,更高
胆碱和肌醇,表明神经元完整性降低和炎症增加)]将被
作为一个调解人(目标2)。我们还将探讨不同的抑郁症状领域[1)认知,2)
情感,和3)躯体领域以及4)冷漠和5)快感缺乏],作为初步证据显示的症状
具体到艾滋病毒感染,如躯体症状和冷漠,这可能提供深入了解划定NIP-
脑区-症状网络(Aim 3)。R 01研究中收集的许多类型的数据将与
这种R21,如社会人口统计学;临床;心理和行为;和神经成像数据,最大化
R21的可行性。我们同时调查了三个NIP途径,并制定了详细的分析计划,
预测抑郁症状将提供一个机会,获得机械知识超越血浆
炎症标志物-抑郁症的关联,并告知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:$15.75万
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Autonomic and Immuno-vascular Mechanisms of Antihypertensive Effects of Taichi
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资助金额:$74.59万
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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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Role of obesity on vascular inflammation and immune cell activation in prehyperte
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批准号:8011511
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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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Role of obesity on vascular inflammation and immune cell activation in prehyperte
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批准号:7590157
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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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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