海洛因成瘾者冲动控制障碍的神经网络基础及遗传风险因素研究

Heroin is the major addictive drug with the highest popularity in China and all over the word, which brought great harm to not only individuals but also the whole society. In the cycling course of drug addiction, impulsivity plays a critical role on the starting, maintenance, and recidivism of drug use, which is significantly affected by genetic and environmental factors. So it is crucial for the prevention and treatment of addiction to clarify the neural basis and influence factors of high impulsivity in addicts. However, it is still lack of research reports in this area so far. We assume that the impulsive drug use would be the consequence of the disrupted interaction between impulsivity driven and impulsivity control systems. Here, by employing the network analysis methods, we aim to explore the disrupted characteristics of impulsivity-control dual system in heroin addicts. Then we will screen the risk genetic variation, based on the classic mechanism of addiction and impulsivity, which may affect these changes. Furthermore, the interactive effects of the epigenetic modifications will be assessed. At last, we will verify the predictive effects of the network and genetic markers on heroin addiction according to the fMRI experiments. The findings would contribute to the development of comprehensive pre-warning strategy and precise therapy in heroin addiction.

海洛因是世界上滥用最为广泛且成瘾性极强的精神活性物质之一，给个人和社会带来了巨大的危害。冲动水平增高是药物成瘾起始、维持及复发的关键风险因素，并受遗传和环境的显著影响。干预并改善成瘾者的冲动水平有望成为成瘾防治的新途径。然而目前关于海洛因成瘾冲动控制障碍的神经基础及遗传影响因素尚缺乏系统研究。冲动行为由冲动驱动及控制系统共同调控，双系统网络之间的连接失衡可能是导致成瘾者冲动控制障碍的根本原因。本项目拟采用脑网络分析方法，研究海洛因成瘾者冲动-控制系统的脑网络特征及其与成瘾行为的关联性，并基于成瘾疾病的分子机制探索影响海洛因成瘾者冲动-控制网络的基因多态性。在此基础上分析环境因素介导的表观遗传修饰对基因多态性及海洛因成瘾的交互影响。最终通过功能影像验证研究，明确脑网络及遗传风险因素对海洛因成瘾发生及发展的预测效能，以期为制定海洛因成瘾的综合预警体系及精准治疗策略提供科学依据。

冲动水平增高是药物成瘾起始、维持及复发的关键风险因素，并受遗传和环境的显著影响。冲动行为由冲动驱动及控制系统共同调控，双系统网络之间的连接失衡可能是导致成瘾者冲动控制障碍的根本原因。课题负责人围绕成瘾相关冲动系统及其遗传风险因素开展了一系列研究。主要内容包括：1）明确海洛因成瘾者的冲动行为学改变特征；2）明确海洛因成瘾者的冲动相关脑网络学特征性改变；3）多层次探索了药物成瘾易感性及冲动相关的遗传风险因素。研究按计划顺利进行并超额完成目标。课题负责人已在Molecular Psychiatry、Addiction Biology等SCI期刊发表论文5篇。研究成果较为全面地明确海洛因成瘾者冲动相关的影像学的表型特征及遗传风险因素，有助于深入理解成瘾的神经机制。

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