Identifying Cognitive and Neural Risk Factors for Substance Dependence in ADHD

描述(申请人提供)：在寻求治疗甲基苯丙胺(MA)依赖的成年人中，注意力缺陷/多动障碍(ADHD)的发病率很高。许多对MA受试者的研究并没有筛查ADHD，因此ADHD和MA依赖之间的协同作用还没有得到系统的研究。拟议的项目将使用功能神经成像和有针对性的认知测量来评估与ADHD和MA依赖相关的认知控制中的行为和神经损害。目的是确定每个临床疾病的独特贡献以及ADHD+MA共病的功能特征。虽然已经有关于ADHD和物质依赖中的奖励和动机因素的研究，但认知控制和行为调节的作用还没有得到充分的研究。ADHD和兴奋剂滥用的共病特别令人感兴趣，因为兴奋剂是ADHD的首选治疗方法。ADHD患者表现出广泛的认知控制缺陷；然而，关于兴奋剂依赖的行为修正的研究一直不太一致。认知控制和行为洞察力对于最佳决策和抵制从事危险行为(例如，寻求毒品)的冲动至关重要。这项提案将研究ADHD和MA依赖中与有害决策相关的认知控制障碍的神经基础。研究对象分为四组：1)有MA依赖但不存在ADHD的受试者；2)有MA依赖并伴有ADHD的受试者；3)无MA依赖的ADHD受试者；4)典型的正常对照组。我们将管理GO/NOGO范例，以产生高错误率，并将进一步检查检测错误并随后修改行为的能力。我们将研究在工作记忆负荷增加以及任务相关神经活动增加的情况下的行为调整。我们的假设是，在记忆负荷增加的情况下，ADHD和MA依赖组(ADHD+MA)将在行为修改和外侧前额叶皮质神经活动减少方面表现出最严重的损害。这一假说是基于ADHD和兴奋剂依赖患者工作记忆所在的脑区先前存在的功能活动受损的基础上。这项拟议研究的结果是在确定物质滥用和ADHD之间相互作用的神经和行为机制以及确定ADHD+MA认知控制障碍方面迈出的重要的第一步。因此，这项提案的目标与NIDA的战略计划四“交叉优先事项”是一致的。 与公共卫生有关：滥用甲基苯丙胺等物质是一个重大的公共卫生问题。ADHD等临床疾病可能会使个人面临更高的物质依赖风险；然而，人们对与ADHD和物质依赖共病相关的神经和认知损害知之甚少。该项目将使用功能神经成像和有针对性的认知测量来调查ADHD和甲基苯丙胺依赖患者在表现监测方面的损害，以及这两种障碍之间的相互作用。研究结果将为研究MA依赖中受损的决策，以及ADHD和MA依赖之间的协同作用提供有价值的见解。

DESCRIPTION (provided by applicant): Among adults seeking treatment for methamphetamine (MA) dependence there is a high prevalence of Attention Deficit/Hyperactivity Disorder (ADHD). Many studies in MA subjects do not screen for ADHD, thus the synergistic interaction between ADHD and MA dependence has not been systematically examined. The proposed project will employ functional neuroimaging and targeted measures of cognition to assess behavioral and neural impairments in cognitive control associated with both ADHD and MA dependence. The goal is to identify the unique contributions of each clinical disorder as well as a functional signature of ADHD+MA comorbidity. Although there has been research into reward and motivational factors in both ADHD and substance dependence, the role of cognitive control and behavioral regulation is under-investigated. Comorbidity of ADHD and stimulant abuse is of particular interest, as stimulants are a preferred treatment for ADHD. Individuals with ADHD display a wide range of cognitive control deficits; however, the research on behavior modification in stimulant dependence has been less consistent. Cognitive control and behavioral insight are essential to optimal decision making and resisting impulses to engage in risky behaviors (e.g., drug-seeking). This proposal will examine the neural substrates of cognitive control impairments associated with detrimental decision-making in ADHD and MA dependence. Four groups will be studied: 1) Subjects with MA dependence but not ADHD; 2) subjects with MA dependence and ADHD; 3) ADHD subjects without MA dependence and 4) typically developing controls. We will administer a GO/NOGO paradigm manipulated to produce high error rates and will further examine the ability to detect errors and subsequently modify behavior. We will examine behavioral modification under situations of increasing working memory load as well as task related neural activity. Our hypothesis is that the group with ADHD and MA dependence (ADHD+MA) will display the most profound impairments in behavior modification and reduced neural activity in lateral prefrontal cortex under conditions of increased memory load. This hypothesis is based on pre-existing compromised functional activity in brain regions subserving working memory in ADHD and stimulant dependence. Results from this proposed study represent an important first step in identifying the neural and behavioral mechanisms of the interaction between substance abuse and ADHD and determining cognitive control impairments in ADHD+MA. Thus the goal of this proposal is consistent with NIDA's strategic plan IV "Cross-Cutting Priorities." PUBLIC HEALTH RELEVANCE: The abuse of substances such as methamphetamine represents a major public health concern. Clinical disorders such as ADHD may put individuals at an increased risk for substance dependence; yet little is known about the neural and cognitive impairments associated with ADHD and substance dependence comorbidity. This project will use functional neuroimaging and targeted measures of cognition to investigate impairments in performance monitoring in ADHD and methamphetamine dependence as well as the interaction between the two disorders. Results will provide valuable insight into impaired decision-making in MA dependence but also the synergistic interaction between ADHD and MA dependence.