The Neurogenetic Basis of Behavioral Inhibition

行为抑制的神经遗传学基础

• 批准号: 7223591
• 负责人: ELIZA J CONGDON
• 金额: $ 2.95万
• 依托单位: STATE UNIVERSITY NEW YORK STONY BROOK
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-29 至 2008-06-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7223591
• 关键词: adolescence (12-20); behavioral /social science research tag; behavioral genetics; brain electrical activity; brain imaging /visualization /scanning; brain mapping; brain subcortex; catechol methyltransferase; child behavior; clinical research; dopamine transporter; frontal lobe /cortex; gene expression; genetic polymorphism; human subject; impulsive behavior; mathematical model; neurogenetics; predoctoral investigator; psychophysiology; young adult human (21-34)

DESCRIPTION (provided by applicant): There is increasing interest and research into the roles that genes and brain systems play in influencing psychiatric illnesses, but a major obstacle in identifying these influences is the complex nature of diagnostic categories. A potential solution is to focus on intervening variables, or endophenotypes, that are likely more sensitive to the effects of genetic variation or brain systems than are heterogeneous, non-biologically-based diagnostic categories. Such an endophenotype is impulsivity, the predisposition to respond to stimuli without considering the consequences. Impulsivity ranges from normal to pathological and characterizes many forms of psychopathology. Although there is evidence supporting a neural basis of impulsivity, and evidence supporting the role of dopamine in influencing impulsivity, there have been only limited attempts to combine this information to identify the neurogenetic bases of impulsivity. This project will test the hypothesis that variants of two dopamine system-related genetic polymorphisms (DAT and COMT) influence the neural network underlying behavioral inhibition, a more direct expression of impulsivity. Specifically, healthy adults pre-selected for genotypes of the DAT and COMT polymorphisms will perform a Stop-signal task, which measures behavioral inhibition, while they undergo functional magnetic resonance imaging (fMRI). This task was chosen because it directly addresses the ability to inhibit a response; fMRI was chosen because neural activation is likely more sensitive to the effects of genetic variation than self-report, clinical diagnosis, or even behavioral performance alone. Neural activation in specific brain regions, during trials requiring inhibition of a response, will be compared between groups with certain variants of each genotype. The goals of the proposed study are 1) to test whether variants of dopamine genetic polymorphisms influence brain activation during behavioral inhibition; 2) to test whether variants of dopamine genetic polymorphisms influence the relationship between brain regions underlying behavioral inhibition; and 3) to test whether dopamine genetic polymorphisms interact in influencing brain activation during behavioral inhibition. Results of the proposed project will help to elucidate the genetic and neural basis of the ability to inhibit one's behavior. Dysfunction in inhibitory control is of extreme clinical relevance, as elevated deficits in inhibition, or impulsivity, are seen across a range of mental disorders; however, before this is studied in clinical populations, we must first understand how it works in a healthy population. By combining genetic and neural information in a single study, the results may ultimately influence future ways in which we diagnose, classify, and treat forms of mental illness.

描述（由申请人提供）：人们对基因和大脑系统在影响精神疾病方面所发挥的作用越来越感兴趣并进行了越来越多的研究，但识别这些影响的一个主要障碍是诊断类别的复杂性。一个潜在的解决方案是关注干预变量或内表型，它们可能比异质的、非生物学的诊断类别对遗传变异或大脑系统的影响更敏感。这种内表型就是冲动，即对刺激做出反应而不考虑后果的倾向。冲动的范围从正常到病态，是多种形式的精神病理学的特征。尽管有证据支持冲动的神经基础，并且有证据支持多巴胺在影响冲动中的作用，但将这些信息结合起来以确定冲动的神经发生基础的尝试却很有限。该项目将测试以下假设：两种多巴胺系统相关的基因多态性（DAT 和 COMT）的变体影响行为抑制（冲动的更直接表达）背后的神经网络。具体来说，预先选择 DAT 和 COMT 多态性基因型的健康成年人将执行停止信号任务，测量行为抑制，同时接受功能性磁共振成像 (fMRI)。选择这个任务是因为它直接解决抑制反应的能力；选择功能磁共振成像是因为神经激活可能对遗传变异的影响比自我报告、临床诊断甚至行为表现更敏感。在需要抑制反应的试验中，将在具有每种基因型的某些变异的组之间比较特定大脑区域的神经激活。拟议研究的目标是1）测试多巴胺遗传多态性的变体是否影响行为抑制期间的大脑激活； 2）测试多巴胺基因多态性的变异是否影响行为抑制背后的大脑区域之间的关系； 3）测试多巴胺基因多态性是否相互作用，影响行为抑制期间的大脑激活。该项目的结果将有助于阐明抑制一个人行为的能力的遗传和神经基础。抑制控制功能障碍具有极其重要的临床意义，因为在一系列精神障碍中都可以看到抑制或冲动的缺陷增加。然而，在临床人群中进行研究之前，我们必须首先了解它在健康人群中的作用。通过将遗传和神经信息结合在一项研究中，结果可能最终影响我们未来诊断、分类和治疗精神疾病的方式。