Although the diagnoses based on phenomenology have many practical advantages, accumulating evidence shows that schizophrenia and autism spectrum disorder (ASD) share some overlap in genetics and clinical presentation. It remains largely unknown how ASD-associated polygenetic risk contributes to the pathogenesis of schizophrenia. In the present study, we calculated high-resolution ASD polygenic risk scores (ASD PRSs) and selected optimal ten ASD PRS with minimal P values in the association analysis of PRSs, with schizophrenia to assess the effect of ASD PRS on brain neural activity in schizophrenia cases and controls. We found that amplitude of low-frequency fluctuation in left amygdala was positively associated with ASD PRSs in our cohort. Correlation analysis of ASD PRSs with facial emotion recognition test identified the negative correlation of ASD PRSs with negative emotions in schizophrenia cases and controls. Finally, functional enrichment analysis of PRS genes revealed that neural system function and development, as well as signal transduction, were mainly enriched in PRS genes. Our results provide empirical evidence that polygenic risk for ASD contributes to schizophrenia by the intermediate phenotypes of left amygdala function and emotion recognition. It provides a promising strategy to understand the relationship between phenotypes and genotypes shared in mental disorders.

尽管基于现象学的诊断具有许多实际优势，但越来越多的证据表明，精神分裂症和自闭症谱系障碍 (ASD) 在遗传学和临床表现上有一些重叠。与 ASD 相关的多基因风险如何导致精神分裂症的发病机制，在很大程度上仍然未知。在本研究中，我们计算了高分辨率 ASD 多基因风险评分 (ASD PRS) 并选择了具有最小P 的最佳十个 ASD PRSPRS 与精神分裂症的关联分析中的价值，以评估 ASD PRS 对精神分裂症病例和对照组脑神经活动的影响。我们发现左杏仁核的低频波动幅度与我们队列中的 ASD PRS 呈正相关。ASD PRSs 与面部情绪识别测试的相关性分析确定了 ASD PRSs 与精神分裂症病例和对照组的负面情绪的负相关。最后，PRS基因的功能富集分析表明，神经系统功能和发育以及信号转导主要富集在PRS基因中。我们的结果提供了经验证据，表明 ASD 的多基因风险通过左侧杏仁核功能和情绪识别的中间表型导致精神分裂症。