精神分裂症超高危人群转化趋势的预测指标及机制研究

有鉴于精神分裂症病理机制复杂、疗效并不理想，精神分裂症的早期诊断和预防已逐渐成为该病基础和临床研究工作的重点。精神分裂症超高危人群在临床上定义为处于精神分裂症前驱期阶段人群，通过对处于该阶段人群进行早期干预治疗，可以有效延缓甚至阻止疾病的发生。然而，超高危人群的转化趋势有三种，约有1/3的个体症状可能在没有干预治疗的情况下自然缓解，有约1/3长期稳定在超高危状态，仅有1/3左右最终转化为精神分裂症。如何精确预测超高危人群转化趋势，降低早期干预治疗的假阳性率，是目前精神医学研究亟待解决的问题。我们试图通过对超高危人群进行纵向随访研究，分析与超高危人群转化发病相关的大脑结构功能、甲基化修饰、基因表达以及神经认知等指标，鉴定超高危人群转化趋势的预测指标；并通过追踪观察超高危人群脑结构功能、甲基化修饰和基因表达水平的变化在疾病发生发展过程中所发挥的作用，深入解析精神分裂症发生的可能病因和发病机制。

Considering the complex pathological mechanism and the poor treatment outcomes of schizophrenia, early detection and intervention gradually become the key work for the foundational and clinical research in schizophrenia. Ultra-high risk for psychosis (UHP) is defined as individuals at the prodromal stage of schizophrenia. Early intervention in individual at UHP can effectively delay or even prevent the development of the illness. Long-term longitudinal studies suggested that there are clinical outcomes in people at UHP. Nearly 1/3 of individuals at UHP may be naturally relieved without any intervention, about 1/3 of individuals at UHP will remain at the prodromal stage of schizophrenia, and only 1/3 individuals at UHP will eventually develop schizophrenia. In this regard, it will cause adverse effects on false positive individuals if they accept clinical intervention. Unfortunately, it is difficult to accurately predict which individuals at UHP will make a transition to frank illness. To solve this issue, we explore the association between baseline brain structural and functional networks, methylation modifications, gene expression, neurocognitive function and the clinical outcomes of UHP individuals, and to identify the potential biological and clinical predictors for the long-term outcomes in the individuals at UHP. In addition, we also detect the changes of brain structure and function, methylation status and gene expression in individuals at UHP during follow-up, and further to investigate the etiology and pathogenesis of schizophrenia.