难治性精神分裂症幻听机制的神经影像学研究

Treatment-resistant auditory hallucinations in schizophrenia (SCZ) are a major challenge in the treatment of metal disorders. Currently, the neural mechanism behind treatment-resistant auditory hallucinations in SCZ remains unclear, and effective indicators for screening are lacking. To identify corresponding neuroimaging features has important clinical significance for predicting treatment-resistant auditory hallucinations in SCZ. D2 dopamine receptor (DRD2) is currently the primary target of antipsychotics. Our previous studies and literatures showed that hyperfunction of the thalamic-auditory cortical DRD2 pathway might be an important neural mechanism underlying auditory hallucinations in SCZ. However, SCZ patients with treatment-resistant auditory hallucinations who show poor response for antipsychotics (antagonists of DRD2) might have other neural mechanisms in addition to the pathway mentioned above, namely abnormal networks involved in auditory-language-memory information processing. In order to verify this hypothesis, in the present project, we plan to prospectively include SCZ patients with auditory hallucinations, by performing a case-control cross-sectional study and a longitudinal study, with the technique of neuroimaging, observing alterations of structure and function in the thalamic-auditory cortical DRD2 pathway and networks involved in auditory-language-memory information processing between SCZ patients with treatment-resistant auditory hallucinations and responders before and after treatment and their relationship with clinical symptoms. This project will clarify the neural mechanism behind drug resistance, find effective indicators for screening and predicting, and provide theoretical basis for early warning and therapy of treatment-resistant auditory hallucinations in SCZ.

难治性精神分裂症（SCZ）幻听是精神病治疗中的一大难题。目前，难治性SCZ幻听的神经机制尚不明确，发现相应的神经影像学特征对难治性SCZ幻听进行预测具有重要的临床意义。多巴胺D2受体（DRD2）是目前抗精神病药物的主要作用靶点，我们前期的研究及文献表明，丘脑-听觉皮层DRD2通路功能亢进可能是SCZ幻听的重要神经机制；而对于抗精神病药物（DRD2拮抗剂）治疗无效的难治性SCZ幻听可能具有该通路之外的神经机制，即涉及听觉-语言-记忆信息处理网络异常。为验证这一假说，本课题拟前瞻性纳入SCZ幻听患者，通过横向及纵向对照研究，采用神经影像学技术，观察难治性与治疗有效的SCZ幻听患者治疗前后丘脑-听觉皮层DRD2通路及听觉-语言-记忆信息处理网络的结构与功能改变，及其与临床症状的关系，了解难治性SCZ幻听耐药性的神经机制，寻找有效的筛查及预测指标，为早期预警及治疗提供理论依据。

难治性精神分裂症（SCZ）幻听是精神病治疗中的一大难题。目前，难治性SCZ幻听的神经机制尚不明确，发现相应的神经影像学特征对难治性SCZ幻听进行预测具有重要的临床意义。多巴胺D2受体（DRD2）是目前抗精神病药物的主要作用靶点，我们前期的研究及文献表明，丘脑-听觉皮层DRD2通路功能亢进可能是SCZ幻听的重要神经机制；而对于抗精神病药物（DRD2拮抗剂）治疗无效的难治性SCZ幻听可能具有该通路之外的神经机制，即涉及听觉-语言-记忆信息处理网络异常。为验证这一假说，本课题拟前瞻性纳入SCZ幻听患者，通过横向及纵向对照研究，采用神经影像学技术，观察难治性与治疗有效的SCZ幻听患者治疗前后丘脑-听觉皮层DRD2通路及听觉-语言-记忆信息处理网络的结构与功能改变，及其与临床症状的关系，了解难治性SCZ幻听耐药性的神经机制，寻找有效的筛查及预测指标，为早期预警及治疗提供理论依据。