Abstract：
BACKGROUND: Aberrant resting-state functional connectivity is a neuropathological feature of schizophrenia (SCZ). Prior investigations into functional connectivity abnormalities have primarily employed seed-based connectivity analysis, necessitating predefined seed locations. To address this limitation, a data-driven multivariate method known as connectome-wide association study (CWAS) has been proposed for exploring whole-brain functional connectivity.
METHODS: We conducted a CWAS analysis involving 46 patients with SCZ and 40 age- and sex-matched healthy controls. Multivariate distance matrix regression (MDMR) was utilized to identify key nodes in the brain. Subsequently, we conducted a follow-up seed-based connectivity analysis to elucidate specific connectivity patterns between regions of interest (ROIs). Additionally, we explored the spatial correlation between changes in functional connectivity and underlying molecular architectures by examining correlations between neurotransmitter/transporter distribution densities and functional connectivity.
RESULTS: MDMR revealed the right medial frontal gyrus and the left calcarine sulcus as two key nodes. Follow-up analysis unveiled hypoconnectivity between the right medial frontal superior gyrus and the right fusiform gyrus, as well as hypoconnectivity between the left calcarine sulcus and the right lingual gyrus in SCZ. Notably, a significant association between functional connectivity strength and positive symptom severity was identified. Furthermore, altered functional connectivity patterns suggested potential dysfunctions in the dopamine, serotonin, and gamma-aminobutyric acid systems.
CONCLUSIONS: This study elucidated reduced functional connectivity both within and between the medial frontal regions and the occipital cortex in patients with SCZ. Moreover, it indicated potential alterations in molecular architecture, thereby expanding current knowledge regarding neurobiological changes associated with SCZ.
METHODS: We conducted a CWAS analysis involving 46 patients with SCZ and 40 age- and sex-matched healthy controls. Multivariate distance matrix regression (MDMR) was utilized to identify key nodes in the brain. Subsequently, we conducted a follow-up seed-based connectivity analysis to elucidate specific connectivity patterns between regions of interest (ROIs). Additionally, we explored the spatial correlation between changes in functional connectivity and underlying molecular architectures by examining correlations between neurotransmitter/transporter distribution densities and functional connectivity.
RESULTS: MDMR revealed the right medial frontal gyrus and the left calcarine sulcus as two key nodes. Follow-up analysis unveiled hypoconnectivity between the right medial frontal superior gyrus and the right fusiform gyrus, as well as hypoconnectivity between the left calcarine sulcus and the right lingual gyrus in SCZ. Notably, a significant association between functional connectivity strength and positive symptom severity was identified. Furthermore, altered functional connectivity patterns suggested potential dysfunctions in the dopamine, serotonin, and gamma-aminobutyric acid systems.
CONCLUSIONS: This study elucidated reduced functional connectivity both within and between the medial frontal regions and the occipital cortex in patients with SCZ. Moreover, it indicated potential alterations in molecular architecture, thereby expanding current knowledge regarding neurobiological changes associated with SCZ.
摘要：
背景：静息状态功能连接异常是精神分裂症（SCZ）的神经病理学特征。先前对功能连通性异常的调查主要采用基于种子的连通性分析，需要预定的种子位置。为了解决这个限制，已经提出了一种数据驱动的多变量方法,称为全连接组关联研究(CWAS),用于探索全脑功能连接.
方法：我们进行了一项CWAS分析，包括46例SCZ患者和40例年龄和性别匹配的健康对照。利用多变量距离矩阵回归（MDMR）来识别大脑中的关键节点。随后，我们进行了后续的基于种子的连接分析,以阐明感兴趣区域(ROI)之间的特定连接模式.此外,我们通过研究神经递质/转运体分布密度与功能连通性之间的相关性,探索了功能连通性变化与基础分子结构之间的空间相关性.
结果：MDMR显示右内侧额回和左钙沟为两个关键节点。随访分析揭示了右内侧额上回和右梭状回之间的连通性不足，以及SCZ中左钙沟和右舌回之间的连通性不足。值得注意的是,研究发现,功能连接强度与阳性症状严重程度之间存在显著关联.此外，功能连接模式的改变表明多巴胺的潜在功能障碍，血清素,和γ-氨基丁酸系统。
结论：这项研究阐明了SCZ患者内侧额叶区域和枕骨皮质内部和之间的功能连接降低。此外，它表明了分子结构的潜在改变，从而扩大与SCZ相关的神经生物学变化的现有知识。
方法：我们进行了一项CWAS分析，包括46例SCZ患者和40例年龄和性别匹配的健康对照。利用多变量距离矩阵回归（MDMR）来识别大脑中的关键节点。随后，我们进行了后续的基于种子的连接分析,以阐明感兴趣区域(ROI)之间的特定连接模式.此外,我们通过研究神经递质/转运体分布密度与功能连通性之间的相关性,探索了功能连通性变化与基础分子结构之间的空间相关性.
结果：MDMR显示右内侧额回和左钙沟为两个关键节点。随访分析揭示了右内侧额上回和右梭状回之间的连通性不足，以及SCZ中左钙沟和右舌回之间的连通性不足。值得注意的是,研究发现,功能连接强度与阳性症状严重程度之间存在显著关联.此外，功能连接模式的改变表明多巴胺的潜在功能障碍，血清素,和γ-氨基丁酸系统。
结论：这项研究阐明了SCZ患者内侧额叶区域和枕骨皮质内部和之间的功能连接降低。此外，它表明了分子结构的潜在改变，从而扩大与SCZ相关的神经生物学变化的现有知识。
