Department of Radiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.
Schizophr Bull. 2019 Oct 24;45(6):1291-1299. doi: 10.1093/schbul/sbz014.
Emerging evidence indicates that a disruption in brain network organization may play an important role in the pathophysiology of schizophrenia. The neuroimaging fingerprint reflecting the pathophysiology of first-episode schizophrenia remains to be identified. Here, we aimed at characterizing the connectome organization of first-episode medication-naïve patients with schizophrenia. A cross-sectional structural and functional neuroimaging study using two independent samples (principal dataset including 42 medication-naïve, previously untreated patients and 48 healthy controls; replication dataset including 39 first-episode patients [10 untreated patients] and 66 healthy controls) was performed. Brain network architecture was assessed by means of white matter fiber integrity measures derived from diffusion-weighted imaging (DWI) and by means of structural-functional (SC-FC) coupling measured by combining DWI and resting-state functional magnetic resonance imaging. Connectome rich club organization was found to be significantly disrupted in medication-naïve patients as compared with healthy controls (P = .012, uncorrected), with rich club connection strength (P = .032, uncorrected) and SC-FC coupling (P < .001, corrected for false discovery rate) decreased in patients. Similar results were found in the replication dataset. Our findings suggest that a disruption of rich club organization and functional dynamics may reflect an early feature of schizophrenia pathophysiology. These findings add to our understanding of the neuropathological mechanisms of schizophrenia and provide new insights into the early stages of the disorder.
新出现的证据表明，大脑网络组织的破坏可能在精神分裂症的病理生理学中发挥重要作用。反映首发精神分裂症病理生理学的神经影像学特征仍有待确定。在这里，我们旨在描述首发未经药物治疗的精神分裂症患者的连接组组织。进行了一项使用两个独立样本的横断面结构和功能神经影像学研究（主要数据集包括 42 名未经药物治疗、未经治疗的首发患者和 48 名健康对照者；复制数据集包括 39 名首发患者[10 名未经治疗的患者]和 66 名健康对照者）。通过扩散加权成像（DWI）得出的白质纤维完整性测量值以及通过结合 DWI 和静息状态功能磁共振成像测量的结构功能（SC-FC）耦合来评估大脑网络结构。与健康对照组相比，未经药物治疗的患者的连接组丰富俱乐部组织明显受到破坏（P =.012，未校正），患者的丰富俱乐部连接强度（P =.032，未校正）和 SC-FC 耦合（P <.001，经假发现率校正）降低。在复制数据集中也发现了类似的结果。我们的研究结果表明，丰富俱乐部组织和功能动力学的破坏可能反映了精神分裂症病理生理学的早期特征。这些发现增加了我们对精神分裂症神经病理学机制的理解，并为该疾病的早期阶段提供了新的见解。
