Psychogenetic Factors in Project REACH

描述（由申请人提供）：提交的K 01指导科学家职业发展奖申请将为Nicole Nugent博士提供正式和量身定制的培训，这对她在精神功能遗传预测因子方面的研究项目至关重要（例如，抑郁、焦虑、物质滥用），健康行为（例如，药物依从性，性风险），和健康结果（例如，CD 4/CD 8淋巴细胞、HIV-1血浆RNA水平、细胞因子和自然杀伤细胞）。鉴于YLH证据水平表明，预期不依从抗逆转录病毒治疗方案会导致耐药性和病毒学失败，从而增加耐药菌株传播给他人的可能性，因此，阐明可能影响健康行为的因素的公众和患者健康相关性是实质性的。选择遗传变异可能会影响患者的健康结果，通过其对协同神经生物学和心理行为过程的影响。遗传样本和纵向数据收集，通过达到卓越的青少年护理和健康（REACH）项目提供了一个独特的，具有成本效益的机会来检查这些目标。此外，拟议的研究非常适合Nugent博士的职业和培训目标：（1）获得足够的分子遗传学培训，以允许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状况的遗传变异的高级统计建模的专业知识，（3）熟悉遗传对艾滋病毒传播和感染后疾病进展的影响，（4）在遗传研究和对污名化人群的研究中进一步敏感地考虑伦理问题，并在精神病学遗传学和青少年艾滋病毒科学领域建立自己的贡献者。这些培训目标将通过正式课程和研讨会，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。该K 01奖将允许培训和研究成果，以支持未来计划的投资回报率和创新研究的YLH方案线。公共卫生相关性：虽然抗逆转录病毒治疗在YLH中提供了显着的健康收益，但这些收益受到患者依从性的限制。不遵守规定会导致艾滋病毒耐药株的出现。通过对心理行为和/或神经生物学过程的影响，确定可能导致YLH健康结局的因素，将允许为YLH制定知情的行为和药理干预措施。

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.