Neural Mechs of Cognition in ADHD & Externalizing Behav

描述(由申请人提供)：了解与外化行为(EB)相关的认知缺陷所涉及的神经生物学机制有可能为EB的病因、症状学以及预防和治疗EB的可能性提供洞察力，包括亚临床和ADHD、品行障碍和反社会人格障碍等障碍。利用成像基因组学，这项研究将研究与EB相关的认知缺陷的神经机制，如冲动和攻击性。我将把重点放在具有多巴胺受体特定变体的个体的智商(IQ)上，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受体基因的一个特定变种(DRD4)完全减弱了EB与智商的负关联(r=0.02vs.r=-0.43)。64名参与者接受了相关DRD4变异的筛查，他们在执行认知和情感任务时将接受功能磁共振扫描，并将接受EB、智力和其他个体差异的评估。我预测，在认知和情感挑战期间，DRD4的变异将分别调节背外侧和腹外侧PFC的大脑活动。将在几个现有数据集中进行相关分析。其中三名儿童(被监禁或被诊断为ADHD)已被分型为DRD4基因多态，而第四名由有功能磁共振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.