Psychogenetic Factors in Project REACH

描述(由申请者提供)：提交的K01指导科学家职业发展奖的申请将为Nicole Nugent博士提供正式和量身定制的培训，这对于她在青年艾滋病毒感染者(YLH)中精神功能(例如抑郁、焦虑、药物滥用)、健康行为(例如服药依从性、性风险)和健康结果(例如CD4/CD8淋巴细胞、HIV-1血浆RNA水平、细胞因子和自然杀伤细胞)的遗传预测研究路线的研究是必要的。鉴于YLH的证据水平表明，不遵守抗逆转录病毒疗法预计会导致耐药性和病毒学失败，从而增加将耐药株传播给其他人的可能性，因此阐明可能影响健康行为的因素与公众和患者健康相关的意义重大。选择的遗传变异可能通过对协同神经生物学和心理行为过程的影响来影响患者的健康结果。通过追求卓越青少年护理和健康(REACH)项目收集的遗传样本和纵向数据为检验这些目标提供了一个独特的、具有成本效益的机会。此外，拟议中的研究非常适合纽金特博士的职业生涯和培训目标：(1)获得足够的分子遗传学培训，以便与分子遗传学和其他科学家进行知情的多学科研究合作；(2)获得影响人类行为和精神疾病的遗传变异的高级统计模型方面的专业知识；(3)熟悉影响艾滋病毒传播和感染后疾病发展的基因影响；(4)在基因研究和研究中对伦理考虑进一步敏感，以及对耻辱人群的研究，并在精神病学遗传学和青少年艾滋病毒科学领域确立自己的贡献者地位。这些培训目标将通过正式的课程和研讨会、使用REACH和导师数据的应用培训经验以及持续的密切指导相结合来实现。这一K01奖项将允许培训和研究成果，以支持未来计划的ROI和与YLH的创新研究计划线。公共卫生相关性：尽管抗逆转录病毒治疗在青壮年获得了显著的健康收益，但这些益处受到患者依从性的限制。不坚持会导致艾滋病毒耐药株的出现。确定可能通过对心理、行为和/或神经生物学过程的影响而影响青少年儿童健康结果的因素，将有助于为青少年儿童制定知情的行为和药物干预措施。

DESCRIPTION (provided by applicant): The submitted application for a K01 Mentored Scientist Career Development Award will afford Dr. Nicole Nugent formal and tailored training essential for her programmatic line of research in genetic predictors of psychiatric functioning (e.g., depression, anxiety, substance abuse), health behaviors (e.g., medication adherence, sex risk), and health outcomes (e.g., CD4/CD8 lymphocytes, HIV-1 plasma RNA levels, cytokines, and natural killer cells) in youth living with HIV (YLH). Given that YLH evidence levels of non- adherence to antiretroviral regimens expected to result in drug resistance and virologic failure, thereby increasing likelihood of transmission of drug-resistant strains to others, the public and patient health relevance elucidating factors that may influence health behaviors is substantial. Select genetic variants may influence patient health outcomes via their effects on synergistic neurobiological and psychobehavioral processes. Genetic samples and longitudinal data collected through the Reaching for Excellence in Adolescent Care and Health (REACH) Project provide a unique, cost-effective opportunity to examine these aims. Additionally, the proposed research is ideally suited to Dr. Nugent's career and training goals to: (1) obtain sufficient training in molecular genetics to permit informed multidisciplinary research collaborations with molecular genetics and other scientists, (2) gain expertise in advanced statistical modeling of genetic variants influencing human behavior and psychiatric conditions, (3) obtain familiarity with genetic influences on HIV transmission and post-infection disease progression, (4) further sensitivity to ethical considerations in genetic research and research with stigmatized populations, and to establish herself as a contributor within the psychiatric genetic and adolescent HIV scientific fields. These training goals will be achieved through a combination of formal coursework and workshops, applied training experiences using REACH and mentor data, and ongoing close mentorship. This K01 award will permit training and research findings to support future planned ROIs and programmatic line of innovative research with YLH. PUBLIC HEALTH RELEVANCE: Although antiretroviral therapy has afforded marked health gains in YLH, these benefits are limited by patient adherence. Non-adherence results in emergence of drug-resistant strains of HIV. Identification of factors that may contribute to health outcomes in YLH via their effects on psychobehavioral and/or neurobiological processes will permit the development of informed behavioral and pharmacologic interventions for YLH.