强迫性对药物成瘾行为的调控及其前额叶-反奖赏系统神经机制

强迫性是一种与不顾严重后果的固着行为密切相关的神经心理结构，大脑神经系统中强迫性行为调控机制崩溃是导致药物成瘾的直接原因。以往研究对于大脑奖赏系统（中脑-皮层-边缘神经环路）在成瘾行为中的作用及机制已经具有丰富的了解，但针对药物成瘾的强迫性特征本身以及前额叶-反奖赏系统神经环路在成瘾行为中的作用机制了解有限，尤其是缺乏对药物成瘾强迫性特征的系统考察、缺少遗传学研究以及非兴奋剂类药物的汇聚证据。本项目拟采用人类成瘾行为与遗传学视角（海洛因成瘾者与其无药物使用的一级亲属如兄弟姐妹的对照），结合神经认知、神经生理（事件相关脑电位, ERPs）、神经影像学（功能性磁共振成像, fMRI）等不同层面的方法和技术，对药物成瘾强迫性机制的外在表征、神经生物学基础以及与个体差异有关的遗传易感性进行探索，期在进一步识别药物成瘾行为的关键神经生物通路、为探寻潜在的药物或非药物干预靶点提供更多实证依据。

Compulsivity is a basic neuropsychological element connected to perseverations and persistent behaviors that are continued in the face of adverse consequences. It has been well assumed that breakdown of the regulatory mechanisms on compulsivity within the neural systems could be a primary cause of drug addiction. Progress in addiction studies from recent decades has manifested a key role of the brain reward system (i.e. mesocorticolimbic circuitry) implicated in addictive behaviors. However, there is little knowledge of compulsivity per se acting in the development of drug addiction, as such for mechanisms of the prefrontal cortex-anti-reward system circuitry. Particularly, there is lack of a systematic investigation of compulsivity traits linked to substance use disorders, as well as genetic family research and convergent evidence from non-stimulants drugs (e.g. opiates). In this project, we intended to investigate the compulsivity profiles of heroin addicts and their healthy drug-free first-degree relatives (i.e. siblings) compared to healthy controls, combining a genetic perspective with human addictive behaviors. Neurocognitive tasks, as well as cognitive event-related brain potentials (ERPs) and neuroimaging methods (functional magnetic resonance imaging, fMRI), were employed to assess compulsivity facets and possible neurophysiological correlates among the three above-mentioned subject groups, aiming to probe into the hereditary feasibility and neural bases of compulsivity implicated in drug addition. This project might be conducive to future discernment of medical or non-medical intervention targets of addictive disorders.