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: 7808853
• 负责人: Erin elizabeth Sundermann
• 金额: $ 3.25万
• 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/7808853
• 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; 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）：本申请提出了一个旨在确定人类免疫缺陷病毒（HIV）认知性能和脑功能障碍的遗传预测的培训前培训计划。该培训计划涉及三个主要领域的指导，教学和体验研究培训：1）HIV，2）功能磁共振成像（fMRI）和3）心理遗传学。该候选人旨在建立fMRI和遗传学的先前培训，并进行论文项目，将这两种方法沿新方向统一。该项目将是实现申请人职业目标的重要一步，以独立研究与遗传标记有关的认知和心理健康。在这个更广泛的目标中，拟议的研究培训计划的总体目的是表征儿茶素O-甲基转移酶（COMT）基因（Val158met）对艾滋病毒中年女性认知和大脑功能的共同多态性的影响。在这种特殊疾病中检查这种特殊基因型的动机来自于在健康成年人中受到COMT影响的特定认知和神经机制的大重叠，并且在HIV患者中受到损害。假设是，这种多态性使表征这种疾病的认知脆弱性加剧了。数据表明，VAL158MET多态性会损害前额叶介导的认知和生理反应。 val等位基因与在工作记忆任务期间前额叶皮层的异常激活和降低的加工效率有关。拟议的项目旨在检查Val158met多态性对艾滋病毒中年妇女对执行功能和前额叶皮层功能障碍的影响。将包括来自妇女间艾滋病毒研究（WIHS）的芝加哥遗址的参与者的数据。行为数据将包括N-BACK的表现，并将在常规的WIHS研究访问中收集大约240名妇女。我们预测，与Val/MET/MET/MET基因型相比，Val/Val基因型的认知性能较差，并且与HIV对照组相比，在HIV+女性中，Val/Val基因型的负面影响更为明显。为了研究这种遗传脆弱性的神经底物，在N-BACK检验的性能期间，18名HIV+女性将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，N-BACK期间Val等位基因载体将显示出前额叶皮层活性的增加。这项研究将是第一个评估艾滋病毒人群中COMT Val 158met多态性和认知之间关系的研究。 公共卫生相关性：这些发现将为艾滋病毒+妇女认知功能的遗传预测指标提供洞察力，并将有助于确定可能加剧疾病中执行功能缺陷的危险因素。