A neuroimaging biomarker for striatal dysfunction in schizophrenia
A neuroimaging biomarker for striatal dysfunction in schizophrenia
复制标题
精神分裂症纹状体功能障碍的神经影像生物标志物
DOI：
10.1038/s41591-020-0793-8
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发表时间：
2020-03-23
期刊：
影响因子：
82.9
通讯作者：
Liu, Bing
中科院分区：
文献类型：
--
作者：
Li, Ang;Zalesky, Andrew;Liu, Bing
越来越多的证据表明，精神分裂症患者的纹状体功能和连通性受到破坏（1-5）。我们开发了一种新的假设驱动的神经成像生物标志物，用于精神分裂症的识别、预后和基于功能性纹状体异常（FSA）的亚型。FSA评分提供纹状体功能障碍的个性化指标，范围从正常到高度病理。通过对7台独立扫描仪（n = 1100）获得的功能性磁共振图像进行交叉验证，FSA将精神分裂症患者与健康对照区分开来，准确率超过80%（灵敏度79.3%，特异性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治疗反应显著相关。FSA揭示了纹状体功能障碍在神经精神疾病中的严重程度，其中功能障碍在精神分裂症中最严重，在双相情感障碍中较轻，在抑郁症、强迫症和注意力缺陷多动障碍中与健康个体难以区分。纹状体过度活跃的基因座再现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。总之，我们开发了一种新的纹状体功能障碍的生物标志物，并建立了其在预测抗精神病药物疗效、临床分层和阐明神经精神疾病纹状体功能障碍方面的应用。一种新的交叉验证的反映纹状体功能障碍的神经成像生物标志物可用于区分精神分裂症患者和健康对照，并与抗精神病药物的治疗反应有关。
Mounting evidence suggests that function and connectivity of the striatum is disrupted in schizophrenia(1-5). 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.A new cross-validated neuroimaging biomarker that reflects striatal dysfunctioning can be used to distinguish patients with schizophrenia from healthy controls, and is associated with treatment response to antipsychotics.