Integrated neuroimmune model of problematic substance use and depression in people living with HIV

HIV 感染者有问题的物质使用和抑郁症的综合神经免疫模型

• 批准号: 10700489
• 负责人: Joshua Matthew Schrock
• 金额: $ 17.72万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-01 至 2028-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10700489
• 关键词: Acceleration; Adherence; Age; Aging; Bisexual; Brain; Cardiovascular Diseases; Caring; Chronic; Chronic Disease; Clinical; Clinical Psychology; Cohort Studies; Development; Disease; Emotions; Enrollment; Funding; Gays; Goals; Grant; HIV; Health; Heart Diseases; Individual; Inflammation; Intervention; Life; Literature; Longitudinal cohort study; Malignant Neoplasms; Manuscripts; Mediating; Meditation; Mental Depression; Mental Health; Mentors; Metabolic Diseases; Modeling; Neuroimmune; Neurosciences; Outcome; Pathogenesis; Pattern; Persons; Play; Predisposition; Prevention; Research; Research Personnel; Rest; Risk; Risk Factors; Sampling; Self-control as a personality trait; Sexual and Gender Minority Youth; Stimulus; Stress; Testing; Thinking; Training; Visit; Writing; antiretroviral therapy; assigned male at birth; career; cognitive training; comorbidity; depressive symptoms; disorder prevention; experience; fall risk; follow-up; improved; men; neuroimaging; neuroimmunology; neuroregulation; nonbinary; novel; prevent; programs; reduced substance use; skills; substance use; systemic inflammatory response; therapy adherence; transgender women; young adult

PROJECT SUMMARY Despite major advances in the treatment of HIV, people living with HIV (PLWH) experience greater burdens of multiple aging-related chronic diseases compared to people without HIV. Substance use, depression, and systemic inflammation are risk factors for aging-related chronic diseases and occur at higher rates among PLWH. Research is needed to identify factors that drive substance use, depression, and systemic inflammation among PLWH in young adulthood, at ages when chronic disease prevention is still feasible. The brain’s central executive network (CEN) plays a key role in exerting self-control, reappraising stressful stimuli, and managing intrusive thoughts. These skills are critical for managing negative emotions when facing stressful life circumstances. Lower CEN function may thus increase susceptibility to stress-related mental health outcomes, such as depression and substance use. Among people living with HIV, greater substance use and depression may reduce adherence to antiretroviral therapy (ART). Reduced ART adherence may lead to greater systemic inflammation. Greater systemic inflammation may lead to lower CEN function. Lower CEN function, in turn, may further increase susceptibility to problematic substance use and depression. PLWH may therefore be at risk of falling into a vicious cycle of increased depressive symptoms, increased substance use, lower ART adherence, increased systemic inflammation, and reduced CEN function. This project will test an integrated neuroimmune model of problematic substance use and depression in a sample of young adults living with HIV (n=246) who are enrolled in RADAR, a cohort study of sexual and gender minority youth assigned male at birth (e.g., gay and bisexual men, trans women, non-binary individuals). This project has considerable clinical importance because previous research suggests that CEN function can be improved through interventions such as cognitive training, meditation, and neuromodulation. Improving CEN function may therefore prove to be an important new component of HIV care plans aimed at reducing substance use, improving mental health, maximizing ART adherence, and reducing systemic inflammation among PLWH. To make this novel project feasible, the applicant has assembled a team of mentors with expertise in neuroscience, clinical psychology, and HIV pathogenesis. The applicant’s primary career goal is to establish an independently funded research program on the neuroimmunology of substance use, mental health, and chronic aging-related diseases among people living with HIV (PLWH). To this end, the applicant will receive advanced training and research experience in three interrelated research domains relevant to his career goals: (1) Problematic substance use among PLWH, (2) Neuroimaging of brain connectivity, and (3) Chronic inflammation in PLWH. This project will also provide opportunities and formal training to further develop his skills in manuscript writing, grant development, and project management. Building proficiency in these key skills and research domains will equip the applicant to become an independently funded investigator in HIV research.

项目摘要 尽管在艾滋病毒治疗方面取得了重大进展，但艾滋病毒感染者（PLWH）面临着更大的负担， 与未感染艾滋病毒的人相比，物质使用，抑郁症， 全身性炎症是与衰老有关慢性疾病的危险因素， PLWH。需要研究来确定驱动物质使用，抑郁和全身炎症的因素 艾滋病毒/艾滋病感染者中，在年轻的成年人，在年龄时，慢性病预防仍然是可行的。大脑的中枢 执行网络（CEN）在实施自我控制、重新评估压力刺激和管理中起着关键作用 侵入性的想法。这些技能对于在面对压力的生活时管理负面情绪至关重要 情节因此，较低的CEN功能可能会增加对压力相关心理健康结果的易感性， 例如抑郁症和药物使用。在艾滋病毒感染者中， 可能会降低抗逆转录病毒治疗（ART）的依从性。减少ART依从性可能导致更大的全身性 炎症更大的全身性炎症可能导致CEN功能降低。降低CEN功能，反过来， 可能会进一步增加对有问题的物质使用和抑郁症的易感性。因此，PLWH可能在 陷入抑郁症状增加、物质使用增加、ART降低的恶性循环的风险 粘附，增加全身性炎症和降低CEN功能。该项目将测试一个集成的 HIV感染青年样本中有问题物质使用和抑郁的神经免疫模型 （n=246）入组RADAR，这是一项针对出生时被指定为男性的性和性别少数青年的队列研究 (e.g.,男同性恋和双性恋男性，跨性别女性，非二元个体）。该项目具有相当的临床意义 重要性，因为以前的研究表明，CEN功能可以通过干预改善 如认知训练、冥想和神经调节。因此，改善CEN功能可能会证明， 成为艾滋病毒护理计划的一个重要的新组成部分，旨在减少药物使用，改善心理健康， 最大限度地提高ART依从性，并减少PLWH中的全身炎症。为了让这个新奇的项目 在可行的情况下，申请人组建了一个具有神经科学，临床心理学， 和HIV发病机制。申请人的主要职业目标是建立独立资助的研究 关于物质使用，心理健康和慢性衰老相关疾病的神经免疫学计划， 艾滋病毒感染者（PLWH）。为此，申请人将接受高级培训和研究 在与其职业目标相关的三个相互关联的研究领域的经验：（1）有问题的物质使用 （2）大脑连接的神经成像，和（3）PLWH中的慢性炎症。该项目将 还提供机会和正式的培训，以进一步发展他的技能，在手稿写作，赠款 开发和项目管理。熟练掌握这些关键技能和研究领域将 装备申请人成为一个独立资助的艾滋病毒研究的调查员。