Mounting evidence suggests that function and connectivity of the striatum is disrupted in schizophrenia^1,2,3,4,5. We have developed a new hypothesis-driven neuroimaging biomarker for schizophrenia identification, prognosis and subtyping based on functional striatal abnormalities (FSA). FSA scores provide a personalized index of striatal dysfunction, ranging from normal to highly pathological. Using inter-site cross-validation on functional magnetic resonance images acquired from seven independent scanners (n = 1,100), FSA distinguished individuals with schizophrenia from healthy controls with an accuracy exceeding 80% (sensitivity, 79.3%; specificity, 81.5%). In two longitudinal cohorts, inter-individual variation in baseline FSA scores was significantly associated with antipsychotic treatment response. FSA revealed a spectrum of severity in striatal dysfunction across neuropsychiatric disorders, where dysfunction was most severe in schizophrenia, milder in bipolar disorder, and indistinguishable from healthy individuals in depression, obsessive-compulsive disorder and attention-deficit hyperactivity disorder. Loci of striatal hyperactivity recapitulated the spatial distribution of dopaminergic function and the expression profiles of polygenic risk for schizophrenia. In conclusion, we have developed a new biomarker to index striatal dysfunction and established its utility in predicting antipsychotic treatment response, clinical stratification and elucidating striatal dysfunction in neuropsychiatric disorders.

越来越多的证据表明，精神分裂症^1,2,3,4,5纹状体的功能和连接性被破坏。我们开发了一种新的假设驱动的神经影像学生物标志物，用于基于功能性纹状体异常 (FSA) 的精神分裂症识别、预后和亚型分类。FSA 评分提供了纹状体功能障碍的个性化指数，范围从正常到高度病理。对从七个独立扫描仪（n = 1,100)，FSA 将精神分裂症患者与健康对照组区分开来，准确度超过 80%（敏感性为 79.3%；特异性为 81.5%）。在两个纵向队列中，基线 FSA 评分的个体间差异与抗精神病药物治疗反应显着相关。FSA 揭示了神经精神疾病中纹状体功能障碍的严重程度，其中精神分裂症的功能障碍最严重，双相情感障碍的功能障碍较轻，并且与抑郁症、强迫症和注意力缺陷多动障碍的健康个体无法区分。纹状体多动位点概括了多巴胺能功能的空间分布和精神分裂症多基因风险的表达谱。综上所述，