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In Vivo Targeting of Neuroactive Steroid and Immune Networks for Depression in People Living with HIV.

体内靶向神经活性类固醇和免疫网络治疗艾滋病毒感染者的抑郁症。

基本信息

批准号：
10843494
负责人：
Shibani Sharon Mukerji
金额：
$ 24.97万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-09-08 至 2027-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10843494
关键词：
Address Administrative Supplement Affect Age Aging Ambulatory Care Facilities Atrophic Biological Biological Markers Blood Brain Caring Cerebral small vessel disease Cessation of life Cholesterol Clinic Clinical Clinical Trials Design Cognition Corpus striatum structure Data Dementia Depressed mood Development Diagnostic Disease Elderly Enrollment Environment Goals HIV Hippocampus Hormones Image Image Analysis Imaging technology Immune Impaired cognition Infrastructure Insula of Reil Intervention Intervention Studies Investigation Lesion Machine Learning Magnetic Resonance Imaging Major Depressive Disorder Manuscripts Measures Memory Mental Depression Methods Modeling Monitor Morbidity - disease rate Neurology Neuropsychology Outpatients Parents Participant Pathologic Pathology Patient Monitoring Performance Persons Population Positioning Attribute Pregnenolone Provider Quality of life Research Research Personnel Resolution Risk Risk Factors Selection Criteria Techniques Therapeutic Treatment Efficacy United States United States National Institutes of Health White Matter Disease White Matter Hyperintensity age related aging population analysis pipeline antiretroviral therapy brain volume cerebral atrophy clinical infrastructure cohort comorbidity cost cost effectiveness depressive cognitions depressive symptoms diagnostic tool disability efficacy trial epidemiology study experience gray matter high standard imaging detection in vivo machine learning algorithm magnetic field modifiable risk nervous system disorder neuroimaging neuroimaging marker neuropathology neuropsychiatric disorder neurosteroids novel open source point of care point of care testing portability predictive marker randomized placebo-controlled clinical trial tool treatment response trial design

项目摘要

PROJECT SUMMARY Older people with HIV (PWH) in the United States are a rapidly expanding group and are at increased risk for depression and cognitive impairment despite virologic suppression. While major depressive disorder is a critical contributor to reduced quality of life and currently affects 20-40% of PWH, there are no effective diagnostics and limited therapeutics to predict disease and mitigate morbidity in PWH on antiretroviral therapy. As more providers in HIV clinics care for an aging population with HIV, we recognize the need for accessible diagnostics to assess neuropathology in clinical settings and interventional studies. We also recognize the need to consider depression subtypes unique to older people with HIV before initiating effective antidepression therapies. Recent advances in magnetic resonance imaging (MRI) technology allow for low magnetic field strength imaging (LF-MRI) at 1/10th the cost of conventional, high-field MRI, and can be performed outside of the controlled access environments of an MRI suite. This will enable portable LF- MRI to become part of a clinical repertoire of diagnostic tools in neurology clinics and in clinical trial design for neuropsychiatric diseases. Assessing the diagnostic performance of this point-of-care neuroimaging tool for evaluating depression and cognitive impairment in cohorts of older PWH on antiretroviral therapy is critically important. In the parent R01 (MH131194), the PI (Dr. Shibani Mukerji) and research team detailed methods for evaluating a biological subtype of depression related to neuroactive steroids, a cholesterol-derived hormone in people with HIV on antiretroviral therapy. The study is a randomized, placebo-controlled clinical trial of pregnenolone in people with HIV and depression (SOOTHE; NCT05570812). In this administrative supplement, the research team will focus on older PWH (age 55 years and over) with depression, leveraging the SOOTHE infrastructure to investigate the relationship between depression and neuropathology common to older PWH (atrophy and cerebral small vessel disease) using portable LF-MRI. These neuroimaging markers are actively under investigation for age-associated dementia decline in older people without HIV presenting to memory clinics. Data generated from this proposal will be used to expand the SOOTHE model in assessing subtypes of depression amenable to neuroactive steroids and determine the use of LF-MRI in trial design for therapeutic efficacy among people aging with HIV.

项目概要在美国，老年艾滋病毒感染者 (PWH) 是一个迅速扩大的群体，感染艾滋病毒的风险也不断增加尽管病毒学受到抑制，但仍出现抑郁和认知障碍。虽然重度抑郁症是一种生活质量下降的关键因素，目前影响 20-40% 的感染者，但尚无有效的治疗方法诊断和有限的治疗方法可预测疾病并减轻接受抗逆转录病毒治疗的感染者的发病率。随着越来越多的艾滋病毒诊所提供者为感染艾滋病毒的老龄化人群提供护理，我们认识到需要获得可及的服务诊断以评估临床环境和介入研究中的神经病理学。我们也认识到在开始有效的抗抑郁治疗之前，需要考虑老年艾滋病毒感染者特有的抑郁亚型疗法。磁共振成像 (MRI) 技术的最新进展允许低磁场强度成像 (LF-MRI) 的成本仅为传统高场 MRI 的 1/10，并且可以在室外进行 MRI 套件的受控访问环境。这将使便携式 LF-MRI 成为神经病学诊所和神经精神病学临床试验设计的临床诊断工具库疾病。评估这种床旁神经影像工具的诊断性能接受抗逆转录病毒治疗的老年感染者队列中的抑郁和认知障碍至关重要。在母公司 R01 (MH131194)、PI (Shibani Mukerji 博士) 和研究团队详细介绍了评估与神经活性类固醇相关的抑郁症的生物学亚型，神经活性类固醇是患有抑郁症的人的胆固醇衍生激素抗逆转录病毒治疗中的艾滋病毒。该研究是一项针对孕烯醇酮的随机、安慰剂对照临床试验。艾滋病毒感染者和抑郁症患者（SOOTHE；NCT05570812）。在本行政增补中，研究团队将利用 SOOTHE 基础设施，重点关注患有抑郁症的老年 PWH（55 岁及以上）调查抑郁症与老年 PWH 常见的神经病理学（萎缩和脑小血管疾病）使用便携式 LF-MRI。这些神经影像标记物正在积极研究中对前往记忆诊所就诊的未感染艾滋病毒的老年人进行与年龄相关的痴呆症下降的调查。该提案生成的数据将用于扩展 SOOTHE 模型来评估以下子类型：抑郁症适合神经活性类固醇，并确定 LF-MRI 在治疗试验设计中的使用老年艾滋病毒感染者的疗效。