Neuroimaging-based subtyping is increasingly used to explain heterogeneity in psychiatric disorders. However, the clinical utility of these subtyping efforts remains unclear, and replication has been challenging. Here we examined how the choice of neuroimaging measures influences the derivation of neuro-subtypes and the consequences for clinical delineation. On a clinically heterogeneous dataset (total n = 566) that included controls (n = 268) and cases (n = 298) of psychiatric conditions, including individuals diagnosed with post-traumatic stress disorder (PTSD), traumatic brain injury (TBI), and comorbidity of both (PTSD&TBI), we identified neuro-subtypes among the cases using either structural, resting-state, or task-based measures. The neuro-subtypes for each modality had high internal validity but did not significantly differ in their clinical and cognitive profiles. We further show that the choice of neuroimaging measures for subtyping substantially impacts the identification of neuro-subtypes, leading to low concordance across subtyping solutions. Similar variability in neuro-subtyping was found in an independent dataset (n = 1642) comprised of major depression disorder (MDD, n = 848) and controls (n = 794). Our results suggest that the highly anticipated relationships between neuro-subtypes and clinical features may be difficult to discover.

基于神经影像学的亚型越来越多地用于解释精神疾病的异质性。然而，这些亚型分型工作的临床效用仍不清楚，并且复制一直具有挑战性。在这里，我们研究了神经影像学措施的选择如何影响神经亚型的衍生以及对临床描绘的影响。在包括精神疾病的对照 （n = 268） 和病例 （n = 298） 的临床异质性数据集 （总计 n = 566） 上，包括被诊断患有创伤后应激障碍 （PTSD）、创伤性脑损伤 （TBI） 和两者合并症 （PTSD&TBI） 的个体，我们使用结构、静息状态或基于任务的测量确定了病例中的神经亚型。每种模式的神经亚型具有较高的内部效度，但在其临床和认知特征上没有显着差异。我们进一步表明，亚型的神经影像学测量的选择对神经亚型的识别有很大影响，导致亚型分型解决方案的一致性较低。在由重度抑郁症 （MDD， n = 848） 和对照组 （n = 794） 组成的独立数据集 （n = 1642） 中发现了神经亚型的类似变异性。我们的结果表明，神经亚型与临床特征之间备受期待的关系可能难以发现。