BackgroundResistance to antipsychotic treatment affects up to 30% of patients with schizophrenia. Although the time course of development of treatment-resistant schizophrenia (TRS) varies from patient to patient, the reasons for these variations remain unknown. Growing evidence suggests brain dysconnectivity as a significant feature of schizophrenia. In this study, we compared fractional anisotropy (FA) of brain white matter between TRS and non–treatment-resistant schizophrenia (non-TRS) patients. Our central hypothesis was that TRS is associated with reduced FA values.MethodsTRS was defined as the persistence of moderate to severe symptoms after adequate treatment with at least two antipsychotics from different classes. Diffusion-tensor brain MRI obtained images from 34 TRS participants and 51 non-TRS. Whole-brain analysis of FA and axial, radial, and mean diffusivity were performed using Tract-Based Spatial Statistics (TBSS) and FMRIB’s Software Library (FSL), yielding a contrast between TRS and non-TRS patients, corrected for multiple comparisons using family-wise error (FWE) < 0.05.ResultsWe found a significant reduction in FA in the splenium of corpus callosum (CC) in TRS when compared to non-TRS. The antipsychotic dose did not relate to the splenium CC.ConclusionOur results suggest that the focal abnormality of CC may be a potential biomarker of TRS.

中文翻译：

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难治性精神分裂症是否与不同的神经生物学胼胝体连接异常相关？

背景对抗精神病药物治疗的抵抗影响多达 30% 的精神分裂症患者。尽管难治性精神分裂症 (TRS) 发展的时间过程因患者而异，但这些差异的原因仍然未知。越来越多的证据表明，大脑连接障碍是精神分裂症的一个重要特征。在这项研究中，我们比较了 TRS 和非难治性精神分裂症（非 TRS）患者的脑白质分数各向异性（FA）。我们的中心假设是 TRS 与 FA 值降低有关。方法 TRS 被定义为在使用至少两种不同类别的抗精神病药物充分治疗后持续存在中度至重度症状。弥散张量脑 MRI 从 34 名 TRS 参与者和 51 名非 TRS 获得图像。FA和轴向、径向的全脑分析，使用基于区域的空间统计 (TBSS) 和 FMRIB 的软件库 (FSL) 进行平均扩散率，在 TRS 和非 TRS 患者之间产生对比，使用家庭误差 (FWE) < 0.05 进行多重比较校正。结果我们发现与非 TRS 相比，TRS 胼胝体压部 (CC) 的 FA 显着降低。抗精神病药剂量与脾脏CC无关。结论我们的研究结果表明CC的局灶性异常可能是TRS的潜在生物标志物。结果我们发现与非 TRS 相比，TRS 胼胝体压部 (CC) 的 FA 显着降低。抗精神病药剂量与脾CC无关。结论我们的研究结果表明CC的局灶性异常可能是TRS的潜在生物标志物。结果我们发现与非 TRS 相比，TRS 胼胝体压部 (CC) 的 FA 显着降低。抗精神病药剂量与脾CC无关。结论我们的研究结果表明CC的局灶性异常可能是TRS的潜在生物标志物。