Abstract

It has previously been shown that cerebello-thalamo-cortical (CTC) hyperconnectivity is likely a state-independent neural signature for psychosis. However, the potential clinical utility of this change has not yet been evaluated. Here, using fMRI and clinical data acquired from 214 untreated first-episode patients with schizophrenia (62 of whom were clinically followed-up at least once at the 12th and 24th months after treatment initiation) and 179 healthy controls, we investigated whether CTC hyperconnectivity would serve as an individualized biomarker for diagnostic classification and prediction of long-term treatment outcome. Cross-validated LASSO regression was conducted to estimate the accuracy of baseline CTC connectivity for patient-control classification, with the generalizability of classification performance tested in an independent sample including 42 untreated first-episode patients and 65 controls. Associations between baseline CTC connectivity and clinical outcomes were evaluated using linear mixed model and leave-one-out cross validation. We found significantly increased baseline CTC connectivity in patients (P = .01), which remained stable after treatment. Measures of CTC connectivity discriminated patients from controls with moderate classification accuracy (AUC = 0.68, P < .001), and the classification model had good generalizability in the independent sample (AUC = 0.70, P < .001). Higher CTC connectivity at baseline significantly predicted poorer long-term symptom reduction in negative symptoms (R = 0.31, P = .01) but not positive or general symptoms. These findings provide initial evidence for the putative “CTC hyperconnectivity” anomaly as an individualized diagnostic and prognostic biomarker for schizophrenia, and highlight the potential of this measure in precision psychiatry.

中文翻译：

---

小脑-丘脑-皮质超连接对首发精神分裂症患者进行分类并预测长期治疗结果

摘要

先前已经表明，小脑-丘脑-皮质 (CTC) 超连接可能是精神病的状态独立神经特征。然而，尚未评估这种变化的潜在临床效用。在这里，使用 fMRI 和从 214 名未治疗的首发精神分裂症患者（其中 62 名在治疗开始后的第 12 个月和第 24 个月至少进行一次临床随访）和 179 名健康对照获得的临床数据，我们调查了 CTC 超连接性是否会用作诊断分类和预测长期治疗结果的个体化生物标志物。进行了交叉验证的 LASSO 回归以估计基线 CTC 连通性在患者-对照分类中的准确性，在包括 42 名未经治疗的首发患者和 65 名对照的独立样本中测试了分类性能的普遍性。使用线性混合模型和留一法交叉验证评估基线 CTC 连通性和临床结果之间的关联。我们发现患者的基线 CTC 连通性显着增加（P = .01)，治疗后保持稳定。CTC 连通性测量以中等分类准确度（AUC = 0.68， P < .001）将患者与对照组区分开来，并且分类模型在独立样本中具有良好的普遍性（AUC = 0.70，P < .001）。基线时较高的 CTC 连接性显着预测阴性症状的长期症状减少较差（R = 0.31，P = .01），但不是阳性或一般症状。这些发现为假定的“CTC 超连接性”异常作为精神分裂症的个体化诊断和预后生物标志物提供了初步证据，并突出了该措施在精准精神病学中的潜力。