Background

One-third of patients with schizophrenia are treatment-resistant to non-clozapine antipsychotics (TRS), while the rest respond (NTRS). Examining whether TRS and NTRS represent different pathophysiologies is an important step toward precision medicine.

Methods

Focusing on cortical thickness (CT), we analyzed international multi-site cross-sectional datasets of magnetic resonance imaging comprising 110 patients with schizophrenia (NTRS = 46, TRS = 64) and 52 healthy controls (HCs). We utilized a logistic regression with L1-norm regularization to find brain regions related to either NTRS or TRS. We conducted nested 10-fold cross-validation and computed the accuracy and area under the curve (AUC). Then, we applied the NTRS classifier to patients with TRS, and vice versa.

Results

Patients with NTRS and TRS were classified from HCs with 65% and 78% accuracies and with the AUC of 0.69 and 0.85 (p = 0.014 and < 0.001, corrected), respectively. The left planum temporale (PT) and left anterior insula/inferior frontal gyrus (IFG) contributed to both NTRS and TRS classifiers. The left supramarginal gyrus only contributed to NTRS and right superior temporal sulcus and right lateral orbitofrontal cortex only to the TRS. The NTRS classifiers successfully distinguished those with TRS from HCs with the AUC of 0.78 (p < 0.001), while the TRS classifiers classified those with NTRS from HCs with the AUC of 0.69 (p = 0.015).

Conclusion

Both NTRS and TRS could be distinguished from HCs on the basis of CT. The CT pathological basis of NTRS and TRS has commonalities, and TRS presents unique CT features.

中文翻译：

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抗精神病药物治疗抵抗性和反应性精神分裂症皮质异常的维度分布

背景

三分之一的精神分裂症患者对非氯氮平抗精神病药 (TRS) 有治疗耐药性，而其余患者则有反应 (NTRS)。检查 TRS 和 NTRS 是否代表不同的病理生理学是迈向精准医学的重要一步。

方法

以皮层厚度 (CT) 为重点，我们分析了包括 110 名精神分裂症患者 (NTRS = 46, TRS = 64) 和 52 名健康对照 (HCs) 的国际多站点横断面磁共振成像数据集。我们利用 L1 范数正则化的逻辑回归来找到与 NTRS 或 TRS 相关的大脑区域。我们进行了嵌套的 10 折交叉验证并计算了曲线下的准确度和面积 (AUC)。然后，我们将 NTRS 分类器应用于 TRS 患者，反之亦然。

结果

NTRS 和 TRS 患者从 HC 中分类的准确率分别为 65% 和 78%，AUC 分别为 0.69 和 0.85（p  = 0.014 和 < 0.001，已校正）。左颞平面 (PT) 和左前岛叶/额下回 (IFG) 有助于 NTRS 和 TRS 分类器。左侧缘上回仅对 NTRS 有贡献，右侧颞上沟和右侧眶额皮质仅对 TRS 有贡献。NTRS 分类器成功地将 TRS 与 HC 区分开来，AUC 为 0.78（p  < 0.001），而 TRS 分类器将 NTRS 与 HC 区分开来，AUC 为 0.69（p  = 0.015）。

结论

NTRS 和 TRS 都可以在 CT 的基础上与 HC 区分开来。NTRS与TRS的CT病理基础具有共性，TRS呈现独特的CT特征。