自闭症患者情绪障碍及其神经环路机制的研究

Autism spectrum disorders (ASDs) represent severe developmental disorder. The neural substrate for Autism spectrum disorders has been hypothesized to arise from the development of abnormal neural circuits. Previous studies have shown that emotional dysfunction, which is a core symptoms of autism spectrum disorders, can be served as a crucial endophenotypes of ASDs. Emotional dysfunction has many-faceted research values for the mechanism of ASDs. Based on a systematic literature review, we propose that five brain regions implicated in the neural circuits of emotion are the amygdala, the orbitofrontal cortex (OFC), the anterior cingulate cortex(ACC), the superior temporal gyrus(STG) and the hippocampus. Core of the emotional circuits is amygdala which is involved in physiological and behavioral responses. STG and hippocampus may be associated with emotional perception and evaluating the situational information, respectively. In addition, this model suggests a role for the OFC in inhibiting the amygdala’s expression of emotional response whereas a role for the ACC in promoting it. Clinical researches on treatment of ASDs found that some patients experience positive results with drug therapy and others do not. Intranasal Oxytocin and Selective Serotonin Reuptake Inhibitor(SSRI) has been applied in order to assess the therapeutic ef?cacy. Resting functional magnetic resonance imaging and Exact Low Resolution Brain Electromagnetic Tomography(eLORETA) of EEG are used to explore the relationship between brain networks changes and therapeutic effect. And In a further study, sequence of Promoter of SLC6A4 will be analyzed.

自闭症谱系疾病是严重的发育性精神疾病，研究提示自闭症是脑网络水平功能连接障碍异常所致。情绪障碍作为自闭症患者社会功能缺失的核心症状，是自闭症的重要的内表型。情绪神经环路主要涉及杏仁核、颞上回、海马、眶额叶以及扣带回等脑区。其中杏仁核参与情绪的生理行为反应，颞上回与情绪感知有关，海马参与环境信息评估，眶额叶和前扣带回参与情绪调节。从情绪神经环路角度对自闭症神经机制的研究具有重要意义。本研究结合静息态fMRI功能连接、静息态脑功能连接和脑电溯源及分析方法，研究自闭症的情绪环路特征和差异，揭示自闭症的神经机制；采取经鼻给催产素、五羟色胺再摄取抑制剂对低功能自闭症进行干预，比较治疗有效和无效组、治疗前后的情绪环路能网络差异，进一步揭示自闭症情绪环路改变的临床意义。比较SLC6A4启动子5-HTTLPR基因与情绪环路的关系，初步了解其神经回路异常的遗传基础。

建立并完善了面孔情绪加工及疼痛共情的实验范式，收集了大量的被试资源，包括自闭症患者及其一级亲属，多种神经精神疾病患者。研究首先对前额叶环路障碍相关疾病如自闭症、肌萎缩侧索硬化症（ALS）、痴呆做了基因型研究，发现了中国汉族人群ALS和自闭症的易感基因。其次，对国外广泛使用的自闭特质问卷进行汉化，做了信效度的修订，并利用此问筛查出高分组、低分组被试各300例，发现高分组被试存在情绪加工障碍和疼痛共情的受损。对所有被试做了大量的神经心理学测查和ERP相关研究工作，同时对部分研究对象做了多模态的磁共振扫描，发现了与自闭症及共情相关的特异性神经环路。第三，对许多神经精神疾病，如精神分裂症、强迫症、抑郁症、多动症、癫痫、脑损伤、焦虑症、帕金森病等，做了大量的神经心理学测评，包括情绪面孔加工、心理理论、注意网络、决策、生物运动以及双眼竞争等，结果发现这些患者存在多种认知功能受损。第四，对自闭症的干预治疗，如经颅磁刺激和经鼻喷雾催产素进行了研究。