Mental Health and Cognition in HIV Infection in Rakai Uganda
乌干达拉凯艾滋病毒感染者的心理健康和认知
基本信息
- 批准号:10426335
- 负责人:
- 金额:$ 56.69万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-08-22 至 2024-06-30
- 项目状态:已结题
- 来源:
- 关键词:AcuteAddressAdherenceAffectAffectiveAfricaAfrica South of the SaharaAnti-Anxiety AgentsAntidepressive AgentsBasic ScienceBehavioralBiologicalBiological MarkersBiologyBrainCategoriesCerebrovascular DisordersClinical TrialsCocaineCognitionCognitiveCognitive TherapyCohort StudiesComplexDataDiabetes MellitusDimensionsDiseaseEmotionsEnrollmentExposure toFrightFunctional disorderFundingHIVHIV InfectionsHIV SeronegativityHIV-associated neurocognitive disorderHepatitis C co-infectionHeterogeneityHypertensionImpairmentIndividualInflammationInfrastructureInsulinInterventionInvestigationKnowledgeLeadLearningLiteratureLongitudinal cohortMajor Depressive DisorderMeasuresMemoryMental DepressionMental HealthMental disordersMethodologyMotorNIH Office of AIDS ResearchNarcoticsNational Institute of Mental HealthNegative ValenceNervous System PhysiologyNeuraxisNeurocognitive DeficitNeurologyNeuronsNeuropsychological TestsObesityOutcomeParticipantPathogenesisPatternPersonsPharmaceutical PreparationsPhenotypePopulationPrognosisResearchResearch Domain CriteriaResearch PersonnelResearch PriorityRisk FactorsRuralSymptomsSystemTherapeutic InterventionThinkingTraumaTreatment/Psychosocial EffectsUgandaUnited StatesUnited States National Institutes of HealthViolenceViral reservoirVisitWomen&aposs Interagency HIV Studyaccurate diagnosisantiretroviral therapyaxon injurybasebehavioral phenotypingbiomarker panelclinically significantcognitive controlcohortcomorbiditycostdepressive symptomsexosomehypercholesterolemiaillicit drug useimprovedinflammatory markerlow income countrymotor disorderneurofilament protein Lnovelpreservationpsychosocialsubstance usetargeted treatmenttherapy adherence
项目摘要
Mental health disorders including depression and neurocognitive impairment (NCI) are the most common central
nervous system (CNS) complications of HIV infection despite effective antiretroviral therapy (ART). It is estimated
that 40-50% of HIV+ individuals have at least one mental health disorder. Uganda, a low-income country in Sub-
Saharan Africa (SSA) has ~1.5 million people living with HIV (PLWH) many of whom are on ART. Despite ART
use, CNS complications, which are notably heterogeneous, persist among PLWH. Uganda provides a unique
setting for advancing our understanding of major depressive disorder [MDD] and NCI, because common
confounding conditions in the United States such as cerebrovascular disease risk factors and illicit drug use (e.g.,
narcotics, cocaine) are rare in Uganda. We propose to address the overarching hypothesis that there is
substantial heterogeneity in MDD and NCI in PLWH and that psychosocial determinants (e.g., sexual and physical
trauma, violence) are likely contributors to this heterogeneity. Addressing the heterogeneity in MDD and NCI is
critical to advancing our understanding of cognitive phenotypes. To accomplish our aims, we will use a novel
methodology for mental health in HIV research, the NIMH Research Domain Criteria (RDoC) framework, which
recognizes heterogeneity, to first examine behavioral phenotypes among PLWH followed by studies to
understand the functional consequences of these phenotypes and the underlying pathophysiology in these
phenotypes. Our study results should lead to more accurate diagnosis, prognosis, and targeted interventions for
MDD and NCI in HIV infection globally. We plan to cost-effectively leverage the established infrastructure and
data from our previous Rakai Neurology Cohort Study to examine the following aims: Aim 1: Examine separate
and interactive effects of HIV and psychosocial determinants on CNS dysfunction in PLWH. Hyp 1. Exposure to
sexual/physical trauma or violence will interact with HIV in this population and will be associated with greater
impairments/decline in declarative memory, cognitive control, and NVS. Aim 2: Examine effects of psychosocial
determinants and CNS dysfunction on ART adherence in PLWH. Hyp 2. Exposure to sexual/physical trauma or
violence and/or impairments/decline in declarative memory, cognitive control, and NVS will adversely affect ART
adherence. Exploratory Aim 3: Determine biomarkers that relate most strongly and reliably to CNS dysfunction
in the context of HIV and/or psychosocial determinants. Hyp 3: Different biomarkers of neuronal damage and
CNS inflammation will relate to patterns of impairment/decline in declarative memory, cognitive control, motor,
and NVS in the context of HIV and/or exposure to sexual/physical trauma or violence. We will also build capacity
to evaluate and conduct research in mental health disorders and introduce new measures of adherence to our
cohort. Our proposal addresses several high priority research topics for the NIH Office of AIDS Research including
HIV-associated comorbidities, basic research to understand the pathogenesis of mental health disorders in HIV
infection, and research to identify viral reservoirs that could lead to a cure for HIV infection.
包括抑郁症和神经认知障碍(NCI)在内的精神健康障碍是最常见的中枢神经系统疾病。
神经系统(CNS)并发症的艾滋病毒感染,尽管有效的抗逆转录病毒治疗(ART)。据估计
40%-50%的HIV阳性个体至少有一种心理健康障碍。乌干达是一个低收入国家,
撒哈拉非洲(SSA)约有150万艾滋病毒感染者(PLWH),其中许多人正在接受抗逆转录病毒治疗。
使用,中枢神经系统并发症,这是显着的异质性,坚持PLWH。乌干达提供了一个独特的
为了促进我们对重度抑郁症[MDD]和NCI的理解,
美国的混杂疾病,如脑血管疾病风险因素和非法药物使用(例如,
毒品,可卡因)在乌干达是罕见的。我们建议解决的首要假设,有
在PLWH中MDD和NCI显著异质性以及心理社会决定因素(例如,性虐待和身体
创伤、暴力)可能是造成这种异质性的因素。解决MDD和NCI中的异质性是
对我们理解认知表型至关重要。为了实现我们的目标,我们将使用一本小说
艾滋病研究中的心理健康方法,NIMH研究领域标准(RDoC)框架,
认识到异质性,首先检查PLWH之间的行为表型,然后进行研究,
了解这些表型的功能后果以及这些表型中的潜在病理生理学,
表型我们的研究结果应该导致更准确的诊断,预后和有针对性的干预措施,
MDD和NCI在全球HIV感染中的作用我们计划经济高效地利用现有的基础设施,
我们之前的Rakai神经病学队列研究的数据,以检查以下目标:目标1:检查单独的
艾滋病毒和社会心理因素对PLWH中枢神经系统功能障碍的相互作用。Hyp 1.暴露于
性/身体创伤或暴力将与艾滋病毒在这一人群中相互作用,并将与更大的
陈述性记忆、认知控制和NVS的损伤/下降。目标2:检查心理社会影响
决定因素和CNS功能障碍对PLWH患者ART依从性的影响。Hyp 2.遭受性/身体创伤或
暴力和/或陈述性记忆、认知控制和NVS的损伤/下降将对ART产生不利影响
坚持。探索性目标3:确定与CNS功能障碍最强和最可靠相关的生物标志物
在艾滋病毒和/或心理社会决定因素的背景下。Hyp 3:神经元损伤的不同生物标志物,
CNS炎症将涉及陈述性记忆、认知控制、运动、运动神经功能障碍/下降的模式,
在艾滋病毒和/或遭受性/身体创伤或暴力的情况下使用NVS。我们还将建设能力
评估和开展精神健康障碍的研究,并引入新的措施,
队列。我们的提案涉及NIH艾滋病研究办公室的几个高优先级研究课题,包括
HIV相关共病,基础研究了解HIV精神卫生障碍的发病机制
感染,并研究确定病毒水库,可能导致治愈艾滋病毒感染。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Robert H Paul其他文献
Author's Personal Copy Quantitative Tractography Metrics of White Matter Integrity in Diffusion-tensor Mri
作者的个人副本扩散张量磁共振成像中白质完整性的定量纤维束成像指标
- DOI:
- 发表时间:
2008 - 期刊:
- 影响因子:0
- 作者:
Stephen Correia;Stephanie Y Lee;Thom Voorn;David F Tate;Robert H Paul;Song Zhang;S. Salloway;P. Malloy;D. Laidlaw - 通讯作者:
D. Laidlaw
Robert H Paul的其他文献
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{{ truncateString('Robert H Paul', 18)}}的其他基金
Longitudinal determination of nervous system consequences of SARS-CoV-2 in virologically suppressed people with HIV-1 treated in early infection
纵向测定 SARS-CoV-2 对早期感染治疗的病毒学抑制的 HIV-1 患者的神经系统影响
- 批准号:
10613789 - 财政年份:2022
- 资助金额:
$ 56.69万 - 项目类别:
Mental Health and Cognition in HIV Infection in Rakai Uganda
乌干达拉凯艾滋病毒感染者的心理健康和认知
- 批准号:
10663076 - 财政年份:2019
- 资助金额:
$ 56.69万 - 项目类别:
Mental Health and Cognition in HIV Infection in Rakai Uganda
乌干达拉凯艾滋病毒感染者的心理健康和认知
- 批准号:
10252860 - 财政年份:2019
- 资助金额:
$ 56.69万 - 项目类别:
Mental Health and Cognition in HIV Infection in Rakai Uganda
乌干达拉凯艾滋病毒感染者的心理健康和认知
- 批准号:
10000143 - 财政年份:2019
- 资助金额:
$ 56.69万 - 项目类别:
Impact of Treatment on Brain Integrity in the Earliest Stages of HIV Infection
HIV 感染早期阶段治疗对大脑完整性的影响
- 批准号:
10201435 - 财政年份:2017
- 资助金额:
$ 56.69万 - 项目类别:
Viral and Host Determinants of Cognitive Status in Vertically Transmitted HIV
垂直传播艾滋病毒认知状态的病毒和宿主决定因素
- 批准号:
9248128 - 财政年份:2016
- 资助金额:
$ 56.69万 - 项目类别:
Neuropathogenesis of clade C HIV in South Africa
南非 C 型 HIV 的神经发病机制
- 批准号:
7880824 - 财政年份:2009
- 资助金额:
$ 56.69万 - 项目类别:
Neuropathogenesis of clade C HIV in South Africa
南非 C 型 HIV 的神经发病机制
- 批准号:
8090257 - 财政年份:2009
- 资助金额:
$ 56.69万 - 项目类别:
Neuropathogenesis of clade C HIV in South Africa
南非 C 型 HIV 的神经发病机制
- 批准号:
8288810 - 财政年份:2009
- 资助金额:
$ 56.69万 - 项目类别:
Neuropathogenesis of clade C HIV in South Africa
南非 C 型 HIV 的神经发病机制
- 批准号:
7757756 - 财政年份:2009
- 资助金额:
$ 56.69万 - 项目类别:
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