Genetic Predictors of Cognition in HIV+ Women

艾滋病毒女性认知的遗传预测因素

• 批准号: 7626737
• 负责人: Erin elizabeth Sundermann
• 金额: $ 3.23万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7626737
• 关键词: Adult; Affect; Alleles; Area; Back; Behavioral; Brain; Catechols; Chicago; Cognition; Cognitive; Data; Disease; Dose; Functional Magnetic Resonance Imaging; Functional disorder; Genetic; Genetic Markers; Genetic Polymorphism; Genetic Predisposition to Disease; Genotype; Goals; HIV; HIV-2; Individual; Mediating; Mental Health; Mentors; Methods; Motivation; Participant; Performance; Physiological; Population; Prefrontal Cortex; Process; Research; Research Training; Risk Factors; Short-Term Memory; Site; System; Testing; Training; Training Programs; Transferase; Transferase Gene; Visit; Woman; Women' s Group; career; cognitive function; executive function; insight; methionylmethionine; middle age; neuromechanism; novel; pre-doctoral; psychogenetics; public health relevance; relating to nervous system; response; trimethionine; valylvaline

DESCRIPTION (provided by applicant): This application proposes a predoctoral training program aimed at identifying genetic predictors of cognitive performance and brain dysfunction in Human Immunodeficiency Virus (HIV). The training program involves mentored, didactic, and experiential research training in three primary areas: 1) HIV, 2) functional magnetic resonance imaging (fMRI) and 3) psychogenetics. The candidate aims to build on previous training in fMRI and genetics and to conduct a dissertation project that unites the two methods in a novel direction. The project would be an important step in achieving the applicant's career goal to independently research cognition and mental health in relation to genetic markers. Within this broader goal, the general aim of the proposed research training program is to characterize the effect of a common polymorphism of the catechol- O-methyl transferase (COMT) gene, Val158Met, on cognition and brain function in midlife women with HIV. The motivation for examining this particular genotype in this particular disease comes from the large overlap in the specific cognitive and neural mechanisms shown to be affected by COMT in healthy adults and to be impaired in individuals with HIV. The hypothesis is that this polymorphism compounds the cognitive vulnerabilities that characterize this disease. Data suggests that the Val158Met polymorphism impairs prefrontal-mediated cognition and physiological response. The Val allele has been associated with abnormal activation and decreased processing efficiency of the prefrontal cortex during working memory tasks. The proposed project aims to examine the effect of the Val158Met polymorphism on executive function and prefrontal cortex dysfunction in midlife women with HIV. Data will be included from participants of the Chicago site of the Women's Interagency HIV Study (WIHS). Behavioral data will include performance on the N-back and will be collected in approximately 240 women during their routine WIHS study visits. We predict worse cognitive performance with the Val/Val genotype compared with Val/Met and Met/Met genotypes, and that the negative effect of Val/Val genotype would be more pronounced in HIV+ women compared to HIV- controls. To investigate the neural substrates of this genetic vulnerability, 18 HIV+ women will undergo fMRI assessments during performance of an N-back test. It is predicted that Val allele carriers will show increased prefrontal cortex activity during the N-back compared to women without the allele. This study will be the first to evaluate relationships between the COMT Val 158Met polymorphism and cognition in an HIV population. PUBLIC HEALTH RELEVANCE: The findings will provide insight into genetic predictors of cognitive function in HIV+ women and will help identify a risk factor that may compound executive function deficits in the disease.

描述（由申请人提供）：本申请提出了一项博士前培训计划，旨在识别人类免疫缺陷病毒（HIV）认知表现和脑功能障碍的遗传预测因子。该培训计划涉及三个主要领域的指导、说教和体验式研究培训：1) HIV、2) 功能磁共振成像 (fMRI) 和 3) 心理遗传学。候选人的目标是在之前的功能磁共振成像和遗传学培训的基础上，进行一个论文项目，将这两种方法结合到一个新的方向上。该项目将是实现申请人独立研究与遗传标记相关的认知和心理健康的职业目标的重要一步。在这一更广泛的目标中，拟议的研究培训计划的总体目标是表征儿茶酚-O-甲基转移酶（COMT）基因的常见多态性 Val158Met 对感染艾滋病毒的中年女性认知和大脑功能的影响。研究这种特定疾病中这种特定基因型的动机来自于特定认知和神经机制的大量重叠，这些机制在健康成年人中受到 COMT 的影响，而在 HIV 感染者中受到损害。假设这种多态性加剧了这种疾病的认知缺陷。数据表明 Val158Met 多态性损害前额叶介导的认知和生理反应。 Val 等位基因与工作记忆任务期间前额皮质的异常激活和处理效率降低有关。该项目旨在研究 Val158Met 多态性对感染艾滋病毒的中年女性执行功能和前额皮质功能障碍的影响。数据将包括来自女性机构间艾滋病毒研究 (WIHS) 芝加哥站点参与者的数据。行为数据将包括 N 背的表现，并将在例行 WIHS 研究访视期间收集大约 240 名女性的行为数据。我们预测，与 Val/Met 和 Met/Met 基因型相比，Val/Val 基因型的认知表现更差，并且与 HIV 对照相比，Val/Val 基因型对 HIV+ 女性的负面影响更为明显。为了调查这种遗传脆弱性的神经基础，18 名 HIV+ 女性将在进行 N-back 测试期间接受功能磁共振成像评估。据预测，与没有等位基因的女性相比，Val 等位基因携带者在 N-back 期间将表现出增加的前额皮质活动。这项研究将首次评估 HIV 人群中 COMT Val 158Met 多态性与认知之间的关系。 公共健康相关性：这些发现将深入了解艾滋病毒阳性女性认知功能的遗传预测因素，并将有助于确定可能加剧该疾病执行功能缺陷的危险因素。