权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

COMT Genotype and Risky Decision Making in HIV and Methamphetamine Dependence

COMT 基因型与 HIV 和甲基苯丙胺依赖的危险决策

基本信息

批准号：
7914373
负责人：
MARIANA CHERNER
金额：
$ 52.38万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-08-15 至 2012-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7914373
关键词：
4-aminospiroperidol AIDS/HIV problem Acute Addictive Behavior Affect Affective Age of Onset Alcohol or Other Drugs use Alleles Antisocial Personality Disorder Anxiety Area Attention Attention Deficit Disorder Attention deficit hyperactivity disorder Behavior Behavioral Brain Brain Injuries Brain region Catechol O-Methyltransferase Catechols Cognitive Collection Complex Corpus striatum structure Curiosities DOPA decarboxylase DSM-IV Data Decision Making Diagnosis Diagnostic Disinhibition Dopamine Dopamine D1 Receptor Dopamine Receptor Drug Addiction Drug abuse Emotional Environment Environmental Risk Factor Enzymes Equipment Equipment and supply inventories Esthesia Evaluation Exhibits Exploratory Behavior Exposure to Functional disorder Future Gambling Genes Genetic Genetic Polymorphism Genetic Variation Genotype Goals HIV HIV Infections HIV tat Protein Hepatitis C High Prevalence Homeostasis Human Hygiene Hyperactive behavior Impairment Impulse Control Disorders Impulsive Behavior Impulsivity Individual Individual Differences Infection Injecting drug user Injection of therapeutic agent International Intervention Interview Iowa Knowledge Lead Link Literature Maintenance Measurable Measures Mediating Mental Depression Metabolic Metabolism Methamphetamine Methamphetamine dependence Methionine Methods Methyltransferase Modeling Monitor Monoamine Oxidase Monoamine Oxidase A Moods Motor NIH Program Announcements Neurocognitive Neuropsychological Tests Neurotransmitters Outcome Participant Patient Self-Report Pattern Performance Personality Personality Traits Pharmaceutical Preparations Physiological Population Populations at Risk Prefrontal Cortex Prevalence Probability Process Psychophysiology Public Health Recruitment Activity Relative (related person)Reporting Research Research Design Rewards Risk Risk Behaviors Risk Factors Risk Reduction Risk-Taking Role Schedule Short-Term Memory Single Nucleotide Polymorphism Source Stimulus Structure Substance Addiction System Testing Thinking Tyrosine 3-Monooxygenase Unsafe Sex Utah Valine Variant Work analog base behavior measurement cognitive function computerized cost design discounting dopamine system endophenotype executive function experience extracellular flexibility frontal lobe gene environment interaction gene interaction genetic variant high risk high risk sexual behavior improved indexing insight interdisciplinary approach meetings methamphetamine exposure neurobehavioral neuropsychological novel public health relevance relating to nervous system response reuptake reward processing sound success trait transmission process

项目摘要

DESCRIPTION (provided by applicant): Methamphetamine (METH) use is of major public health concern given its prevalence among individuals who are HIV infected and its association with HIV transmission risk behaviors, particularly high-risk sexual behavior. METH use strongly alters brain dopaminergic function. Dopamine (DA) is the primary neurotransmitter involved in the brain's reward system and is associated with impulsive behavior, hypersexuality, and many aspects of cognitive functioning, all of which contribute to decision-making choices that can impact engagement in risk behaviors. Catechol-O-methyltransferase (COMT) is the enzyme responsible for the majority of DA clearance in the frontal cortex, which, along with its connections to subcortical striatal and limbic areas, constitutes the reward-processing and decision-making substrate of the brain. A putative link has been identified between the COMT Val158Met genetic polymorphism and impaired executive functioning. Recent research also suggests a relationship between COMT Val158Met and impulsive tendencies such as novelty seeking. COMT Val alleles are confer a high rate of dopamine clearance, whereas Met alleles confer a low rate. Because both HIV and METH can damage or disrupt the frontostriatal, DA-utilizing brain areas that subserve decision-making, these conditions may interact with the COMT Val158Met genotype to exacerbate risk-taking. Therefore, we propose to investigate the effects of COMT genotype on executive functioning, preexisting impulsive traits, measurable behaviors indicating impulsivity and novelty seeking, as well as decision-making choices, on HIV risk behaviors among individuals with METH dependence and/or HIV infection. We additionally propose to investigate the role of other dopamine system genes (tyrosine hydroxylase, DOPA decarboxylase, monoamine oxidase A and dopamine receptors D1-4) that may be similarly implicated in functions leading to risky decision-making. We will also explore gene-gene interactions and gene-environment interactions (e.g., genotype interacting with amount of METH exposure) that may contribute to the prediction of propensity to engage in risk behaviors. The proposed project aims to elucidate sources of individual variability in vulnerability to DA-related dysfunction and associated risk-taking. Understanding the biologic, neurobehavioral, and personality determinants of risk-taking in the context of METH and HIV can help to explain individual differences in response to risk-reduction interventions and inform the tailoring of future interventions to improve individual success, with the goal of reducing the current rise in HIV-infection rates. PUBLIC HEALTH RELEVANCE: We will take a multidisciplinary approach to understanding the contribution of genetic, neurocognitive, psychophysiologic, and personality determinants of risky decision-making and their relationship to HIV transmission risk behaviors in the context of HIV infection and METH dependence. Findings will add to the understanding of individual differences in response to risk-reduction interventions and have the potential to inform the tailoring of future interventions.

描述(由申请人提供)：甲基苯丙胺(冰毒)的使用是一个重大的公共卫生问题，因为它在艾滋病毒感染者中的流行，以及它与艾滋病毒传播危险行为，特别是高危性行为的关联。冰毒的使用会强烈改变大脑的多巴胺能功能。多巴胺(DA)是参与大脑奖赏系统的主要神经递质，与冲动行为、性欲亢进和认知功能的许多方面有关，所有这些都有助于做出决策选择，从而影响对危险行为的参与。儿茶酚-O-甲基转移酶(COMT)是负责额叶皮质DA清除的主要酶，它与皮质下纹状体和边缘区域的联系一起构成了大脑的奖赏处理和决策底物。COMT Val158Met基因多态与执行功能受损之间可能存在联系。最近的研究还表明，COMT Val158Met与寻求新奇等冲动倾向之间存在关系。Comt Val等位基因具有较高的多巴胺清除率，而Met等位基因则具有较低的清除速率。由于艾滋病毒和冰毒都可以损害或破坏额纹状体，利用DA的大脑区域为决策提供辅助，这些情况可能与COMT Val158Met基因相互作用，加剧风险承担。因此，我们建议调查COMT基因对有冰毒依赖和/或HIV感染的个体的执行功能、先前存在的冲动特征、表明冲动和寻求新奇的可测量行为以及决策选择的影响。此外，我们还建议研究其他多巴胺系统基因(酪氨酸羟基酶、DOPA脱羧酶、单胺氧化酶A和多巴胺受体D1-4)的作用，这些基因可能与导致危险决策的功能类似。我们还将探索基因-基因相互作用和基因-环境相互作用(例如，基因与冰毒暴露量的相互作用)，这可能有助于预测从事危险行为的倾向。拟议的项目旨在阐明易受多巴胺相关功能障碍和相关风险承担影响的个体差异的来源。在冰毒和艾滋病毒的背景下了解冒险的生物、神经行为和个性决定因素，有助于解释对降低风险干预措施的反应的个体差异，并为未来干预措施的调整提供信息，以提高个人的成功，目标是降低目前艾滋病毒感染率的上升。公共卫生相关性：我们将采用多学科方法，在艾滋病毒感染和冰毒依赖的背景下，了解高风险决策的遗传、神经认知、心理生理和个性决定因素的贡献及其与艾滋病毒传播风险行为的关系。研究结果将增加对应对降低风险干预措施的个体差异的理解，并有可能为未来干预措施的定制提供信息。