精神分裂症奖赏预期加工异常的多巴胺机制及其在治疗中的变化

Reward anticipatory processing is fundamental for optimal behavioural choice within our complex environment, which is of great significance for the acquisition of adaptive behavior. Studies have shown that reward anticipatory signals are regulated by the dopamine(DA) system in the brain. Extensive abnormalities within the DA system is one of the most consistent findings in schizophrenia research. These abnormalities include altered DA receptor function and the structure and function deficit of dopaminergic neurones in frontal and striatum regions. Our previous studies found that the structural and functional abnormalities in the striatum were associated with negative symptoms. A large number of studies have consistently found that patients with schizophrenia have significant reward anticipatory processing abnormalities, and these abnormalities are associated with negative symptoms. Some researchers suggested that abnormal reward processing may be the neural basis of negative symptoms. However, the dopaminergic mechanisms underlie these abnormalities are still not clear. In this study, positron emission tomography (PET) and multimodal magnetic resonance imaging (MRI) were used to investigate the dopaminergic mechanisms of abnormal reward processing in schizophrenia and its changes associated with short-term (6 weeks) antipsychotic treatment. This study is of great significance for understanding the neurobiological mechanism of the abnormal reward processing of schizophrenia and promoting the diagnosis and treatment of negative symptoms.

奖赏预期加工是个体在复杂的现实环境中优化自身行为选择的基础，对于适应性行为的习得具有重要意义。研究表明奖赏预期加工信号受脑内多巴胺（DA）系统的调节。广泛的DA系统异常是精神分裂症研究中最一致的发现之一。这些异常包括DA受体功能及额叶、纹状体区域多巴胺能神经元结构和功能异常等。申请人早期研究发现纹状体结构和功能异常与阴性症状相关。大量研究一致发现精神分裂症患者存在显著的奖赏预期加工异常，且这些异常与阴性症状相关。研究者推测奖赏预期加工异常可能是阴性症状产生的神经基础。但奖赏预期加工的DA机制尚不清楚。本研究拟采用正电子发射断层扫描 (PET)和多模态磁共振成像(MRI)考察精神分裂症奖赏预期加工异常的DA机制及其在短期（6周）治疗中的变化。本研究对于理解精神分裂症预期加工异常的神经生物学机制，推进阴性症状的诊断和治疗都有重要意义。

本项目考察精神分裂症患者奖赏学习异常的多巴胺机制及其在治疗中的变化。通过项目执行，招募和测试了共49名精神分裂症患者、58名匹配的健康对照、60名抑郁症患者、50名游戏障碍患者和52名匹配的健康对照。所有被试都按计划完成了基于奖赏学习任务的fMRI扫描、相关行为实验及量表测试。本项目主要有以下发现：1）精神分裂症、抑郁症和网络游戏障碍患者均存在奖赏学习异常且这些异常与临床症状存在关联，但不同疾病中奖赏学习异常的表现模式不同。精神分裂症的奖赏学习异常主要是目标导向学习异常，该异常与多种阴性症状显著关联。2）内囊后肢白质结构缺陷可能是精神分裂症阴性症状的神经生物学标记，且这些白质结构异常与患者免疫系统相关基因变异相关联。3）元认知对健康个体的知觉决策有显著的调节作用，这些调节作用与大脑中目标导向学习系统相关脑区（内侧额叶、背侧前部扣带皮质等）的活动有关，并且精神分裂症和抑郁症患者都表现显著的元认知异常。本研究结果揭示了精神分裂症患者奖赏学习异常的具体模式及其跨诊断差异和元认知调节等特性，为推进精神分裂症阴性症状的诊断和治疗提供了重要的参考。