Understanding The Pathways To Aggression

描述(申请人提供)：以前的研究表明，某些神经心理特征，包括社会情绪信息处理、情绪调节和行为抑制/冲动与攻击性有关。此外，动物和人类损伤证据的趋同突出了特定神经底物的作用，如杏仁核(AMYG)、眶内侧前额叶皮质(OMPFC)和背侧前扣带回皮质(DACC)在社会情绪处理和行为抑制(如认知控制)中的作用。因此，本研究的目的是利用双胞胎样本收集关于特定神经心理特征和脑功能反应性的多模式数据，以阐明可能与攻击行为有关的不同遗传途径。具体地说，我们建议使用一系列基于实验室的神经心理学评估来测量社会情绪信息处理、情绪调节和行为抑制/冲动，这些评估来自我们的PENNTins研究项目的200对成年双胞胎(100 MZ，100 DZ)。此外，我们将进一步对社会情绪信息处理(SEIP)任务中的杏仁核和OMPFC功能进行BOLD敏感的功能磁共振成像(FMRI)研究，并在冲动任务中对dACC功能进行fMRI研究，以评估大脑反应的神经生理学模式。通过研究这些特征与攻击性和相关行为的共同基因的程度，我们有独特的机会通过检测神经心理特征和大脑反应的神经生理模式作为潜在的遗传影响因素对攻击性和相关行为的影响，来“弥合”表型和基因之间的差距。此外，通过将基于理论的多变量模型应用于攻击行为的多模式评估、社会情绪信息处理和冲动，我们也可以开始更好地理解攻击行为的潜在结构。 公共卫生相关性：无论是从从事这些行为的个人的角度，还是从这些行为所针对的人/财产的角度来看，攻击和人际暴力都是世界性的公共卫生问题。关于攻击性的精神病学遗传学研究的目标之一是发现特定的基因变异，这些变异是攻击性和相关疾病的危险因素。然而，基因不太可能直接编码攻击性行为，而是通过间接机制或途径影响行为。为了更好地了解这些潜在的遗传机制，双胞胎研究可以用来识别可能作为攻击性和相关行为的内表型的基于生物的特征。

DESCRIPTION (provided by applicant): Previous studies have suggested that certain neuropsychological traits, including socio- emotional information processing, emotion regulation, and behavioral inhibition/impulsivity are associated with aggression. Moreover, converging lines of animal and human lesion evidence have highlighted the role of specific neural substrates such as the amygdala (AMYG), orbital- medial prefrontal cortex (OMPFC), and dorsal anterior cingulate cortex (dACC) in socio- emotional processing and behavioral inhibition (e.g., cognitive control). Therefore, the goal of the present study is to collect multimodal data on specific neuropsychological traits and functional brain reactivity using a sample of twins in order to elucidate the different genetic pathways that may be related to aggressive behavior. Specifically, we propose to measure socio-emotional information processing, emotion regulation, and behavioral inhibition/impulsivity using a series of laboratory-based neuropsychological assessments in a population-based sample of 200 adult twin pairs (100 MZ, 100 DZ) from our PENNTwins Study Program. In addition, we will further conduct BOLD-sensitive functional magnetic resonance imaging (fMRI) studies of Amygdala and OMPFC function during a socio-emotional information processing (SEIP) task and fMRI studies of dACC function during an impulsivity task to assess neurophsyiological patterns of brain response. By investigating the extent to which these characteristics share common genes with aggression and related behaviors, we have the unique opportunity to "bridge the gap" between phenotype and genotype by examining neuropsychological traits and neurophysiological patterns of brain response as potential mediators of the genetic influence on aggression and related behaviors. Moreover, by applying theoretically-based multivariate models to multimodal assessments of aggression, socio- emotional information processing, and impulsivity, we can also begin to better understand the underlying structure of aggression. Public Health Relevance: Aggression and interpersonal violence are leading worldwide public health problems, both from the viewpoint of the individual who engages in these behaviors and of the people/property that these behaviors target. One of the goals of psychiatric genetic research on aggression is to uncover specific genetic variants that are risk factors for aggression and related disorders. However, it is unlikely that genes code for aggressive behavior directly, but rather influence behavior through indirect mechanisms or pathways. To gain a better understanding of these potential genetic mechanisms, twin studies can be used to identify biologically-based traits that may serve as endophenotpyes for aggression and related behaviors.