脑网络组研究知识库

精神分裂症是一种具有高度异质性的精神疾病，患者多发病于青春期晚期或是成年期早期。青少年精神分裂症患者和不同阶段成人期精神分裂症患者可能具有共同或不同模式的脑功能损伤，探究不同类型精神分裂症患者脑功能损伤模式的共性与特异性有助于更深入地理解精神分裂症的病理生理机制。因此本文基于静息状态功能磁共振影像，比较青少年精神分裂症和不同阶段成人期精神分裂症患者脑功能局部性质与连接性质损伤模式的异同，分析精神分裂症患者随着病程迁移的功能损伤情况，探究在不同类型患者中保持稳定的生物学标记，为进一步理解精神分裂症的病理生理学机制提供线索。

本文首先考察青少年首发精神分裂症患者与不同阶段成人期精神分裂症患者脑功能活动局部一致性的异常模式，反映不同类型精神分裂症患者中固有的脑功能活动异常以及随疾病进程发生变化的脑功能活动异常。具体上，为了探究不同类型的精神分裂症患者局部一致性特征的异常模式，本文首先基于一个包含青少年首发精神分裂症、成人首发精神分裂症、成人慢性精神分裂症以及不同年龄段的正常对照的数据集，提取每个被试的局部一致性特征。接着，通过组间比较分析探究各个类型的精神分裂症患者相比于正常对照在局部特征上的异常模式。最后，结合各组的比较结果，分析不同类型精神分裂症患者局部功能异常的一致性脑区及特异性脑区。结果发现，青少年首发精神分裂症患者及不同阶段成人期患者均在默认模式网络及纹状体处出现显著的局部一致性的异常。其中，青少年首发组与成年首发组的异常模式具有较高的一致性，而成年慢性组患者在更为广泛的脑区中出现了显著的局部特征异常。另外，本文基于体素提取三组比较结果中共有的且变化方向一致的区域，发现三个类型的患者在壳核及腹内侧前额叶处出现了一致的变化，在双侧壳核处局部一致性显著增强，而在腹内侧前额叶处显著减弱。可以看出，壳核及腹内侧前额叶可能是精神分裂症病理生理学机制中的重要节点; 局部一致性的异常在患病初期便存在，且会随着疾病进程发生改变。

壳核及腹内侧前额叶处的局部一致性异常在不同类型的精神分裂症患者中都是稳定存在且模式一致的，然而与之相关的功能连接的变化模式在三种不同类型的患者中是否也完全一致仍未可知。因此本文接着考察了与壳核、腹内侧前额叶两处相关的功能连接在不同类型的精神分裂症患者中的变化模式。首先，本文分别计算了每个被试双侧壳核、腹内侧前额叶三个区域到全脑的功能连接。接着，分别比较每一组患者相比于正常对照的功能连接异常模式。最后，分析各个类型的患者异常模式的共性与特异性, 发现虽然壳核及腹内侧前额叶局部特征的变化模式在不同类型的患者中都是一致的，其功能连接模式仍然存在各自的特点。青少年首发组与成年首发组患者基于腹内侧前额叶的功能连接异常模式相似，与成年慢性组的模式具有较为明显的差异。其中腹内侧前额叶到背外侧前额叶部分区域的连接在各个类型的患者中具有一致的变化模式，提示了该连接可能是精神分裂症中稳定的生物学标记。

综上，本文基于青少年首发精神分裂症及不同阶段成人期精神分裂症的功能磁共振影像数据，对不同类型精神分裂症患者的局部一致性及功能连接特征的异常模式进行了较为系统的比较分析，为理解精神分裂症高度异质的复杂的病理生理学机制提供了一定线索。

Schizophrenia is a highly heterogeneous mental disorder, most of which occur in late adolescence or early adulthood. Adolescent schizophrenia patients and adult schizophrenia patients at different stages may have common or different patterns of brain function damage. Exploring the similarities and differences of brain function damage patterns in different types of schizophrenia patients is helpful to understand the pathophysiology of schizophrenia. Therefore, based on resting-state functional magnetic resonance imaging, this paper compared the similarities and differences of brain functional local properties and connectivity damage patterns between adolescent schizophrenia and adult schizophrenia at different stages, analyzed the functional damage of schizophrenia patients with the course of disease migration, and explored the biological markers that remained stable in different types of schizophrenia patients, so as to provide the possibility for further understanding the correlation between schizophrenia functional damage patterns and clinical manifestations.

Firstly, this paper examined the abnormal patterns of ReHo in adolescent-onset schizophrenia patients and adult schizophrenia patients at different stages, reflecting the inherent abnormal brain function activities in different types of schizophrenia patients and the abnormal brain function activities change with the disease process. Specifically, in order to explore the abnormal patterns of ReHo in different types of schizophrenia patients, this paper extracted the ReHo map of each subject based on a dataset containing adolescent-onset schizophrenia, adult first-episode schizophrenia, adult chronic schizophrenia and healthy controls of different ages. Then, the abnormal patterns of ReHo of various types of schizophrenic patients compared with the healthy controls were explored through comparative analysis between groups. Finally, combined with the comparison results of each group, the common and specific brain regions of ReHo abnormalities in different types of schizophrenia were analyzed. The results showed that there were significant ReHo abnormalities in the default mode network and striatum in adolescent schizophrenia patients and adult patients at different stages. Among them, the abnormal patterns of the adolescent-onset group and the adult first-episode group were highly consistent, while the adult chronic group showed significant ReHo abnormalities in more brain regions. In addition, based on the common and consistent changes in the three groups of voxel extraction results, we found that the three types of schizophrenia patients had consistent changes in the putamen and the ventral medial prefrontal cortex. ReHo was significantly increased in the bilateral putamen, and significantly decreased in the ventral medial prefrontal cortex. It can be seen that the putamen and ventral medial prefrontal cortex may be important nodes in the pathophysiology of schizophrenia. And the abnormality of ReHo exists in the early stage of the disease and changes with the progression of the disease.

The ReHo abnormal patterns of the putamen and ventral medial prefrontal cortex are stable and consistent in different types of schizophrenia patients. However, whether the related functional connectome patterns are completely consistent in three different types of patients is still unknown. Therefore, this paper then investigated the abnormal patterns of functional connectivities related to the putamen and ventral medial prefrontal cortex in different types of schizophrenia patients. Firstly, we calculated the functional connectivities of bilateral putamen and ventral medial prefrontal cortex to the whole brain. Then, the abnormal patterns of functional connectome in each group were compared with healthy controls. Finally, the commonness and specificity of the abnormal patterns of various types of patients were analyzed. We found that although the ReHo patterns of the putamen and ventral medial prefrontal cortex were consistent in different types of schizophrenia patients, their functional connectome patterns were still different. The pattern of functional connectome abnormalities based on the medial prefrontal lobe was similar between the adolescent-onset group and the adult first-episode group, and was significantly different from that of the adult chronic group. The abnormal pattern of connections between the medial prefrontal cortex and the dorsolateral prefrontal cortex was consistent in various types of patients, suggesting that the connections may be a kind of stable biological markers in schizophrenia.

In summary, based on the functional magnetic resonance imaging data of adolescentonset schizophrenia and adult schizophrenia at different stages, this paper systematic compared and analyzed the abnormal functional pattern in patients with different types of schizophrenia, which may provide some clues for understanding the complex pathophysiology mechanism of schizophrenia.