Neural Mechanisms of Cognition in ADHD and Externalizing Behavior

描述（由申请人提供）：了解与外化行为（EB）相关的认知缺陷的神经生物学机制，有可能提供对EB的病因，症状学和预防和治疗的可能性的见解，包括亚临床和疾病，如多动症，品行障碍和反社会人格障碍。利用成像基因组学，本研究将探讨EB相关认知缺陷的神经机制，如冲动性和攻击性。我将重点关注具有多巴胺受体特定变体的个体的智力（IQ）节约，这是我最近在研究生工作中发现的。在三个样本中，多巴胺D4受体基因（DRD4）的特定变体完全减弱了EB和智商的负相关（r = 0.02 vs r = -0.43）。筛选相关DRD4变异的64名参与者将在执行认知和情感任务时进行fMRI扫描，并评估EB、智力和其他个体差异。我预测，在认知和情感挑战中，DRD4变异将分别调节背外侧和腹外侧PFC的大脑活动。将对几个现有数据集进行相关分析。其中三个由儿童（被监禁或被诊断患有多动症）组成，他们已经对DRD4多态性进行了基因分型，而第四个由具有功能磁共振成像数据的健康成年人组成。

DESCRIPTION (provided by applicant): Understanding the neurobiological mechanisms involved in the cognitive deficits associated with externalizing behaviors (EB) has the potential to provide insight into the etiology, symptomatology, and possibilities for prevention and treatment of EB, both subclinically and in disorders such as ADHD, conduct disorder, and antisocial personality disorder. Using imaging genomics, this research will investigate the neural mechanisms involved in cognitive deficits associated with EB, such as impulsivity and aggression. I will focus on the sparing of intelligence (IQ) in individuals with a specific variant of a dopamine receptor, which I have recently discovered in my graduate work. In three samples, a specific variant of the dopamine D4 receptor gene (DRD4) completely attenuated the negative association of EB and IQ (r = .02 vs. r = -0.43). Sixty four participants, screened for the presence of relevant DRD4 variants, will be scanned with fMRI while performing cognitive and affective tasks, and will be assessed for EB, intelligence, and other individual differences. I predict that DRD4 variation will moderate brain activity within dorsolateral and ventrolateral PFC during cognitive and affective challenges, respectively. Related analyses will be done in several existing data sets. Three of these consist of children (incarcerated or diagnosed with ADHD), who have been genotyped for DRD4 polymorphisms, while a fourth consists of healthy adults with fMRI data.