目的:精神分裂症的特征是静息状态自发的大脑活动改变;然而,目前尚不清楚不同空间尺度的变异是否能够有效区分患者和健康对照.此外,这些改变的遗传基础仍然缺乏阐明。我们旨在在这项研究中解决这些问题,以更好地了解精神分裂症的大脑改变及其潜在的遗传因素。
方法:一个由103名诊断为精神分裂症的个体和110名健康对照者组成的队列接受了静息态功能MRI扫描。使用区域同质性(ReHo)度量在四个空间尺度上评估自发性大脑活动:体素水平(1级)和区域水平(2-4:272,53,17个区域,分别)。对于每个空间尺度,多变量模式分析将精神分裂症患者与健康对照进行分类,并进行了转录组-神经影像学关联分析,以建立精神分裂症中基因表达数据与ReHo改变之间的联系。
结果:所有空间尺度的ReHo指标有效地将精神分裂症与健康对照区分开来。量表2显示出最高的分类准确率,为84.6%,其次是1级(83.1%)和3级(78.5%),而量表4的准确度最低(74.2%)。此外,转录组-神经影像学关联分析显示,在4个空间尺度上,不仅存在共有的生物过程,而且存在独特的富集生物过程.这些相关的生物过程主要与免疫反应有关,炎症,突触信号,离子通道,细胞发育,髓鞘形成,和运输活动。
结论:这项研究强调了多尺度ReHo作为精神分裂症诊断中一种有价值的神经影像学生物标志物的潜力。通过阐明这种疾病的ReHo改变的复杂分子基础,这项研究不仅增强了我们对其病理生理学的理解,但也为精神分裂症的基因诊断和治疗的未来发展铺平道路。
OBJECTIVE: Schizophrenia is characterized by alterations in resting-state spontaneous brain activity; however, it remains uncertain whether variations at diverse spatial scales are capable of effectively distinguishing patients from healthy controls. Additionally, the genetic underpinnings of these alterations remain poorly elucidated. We aimed to address these questions in this
study to gain better understanding of brain alterations and their underlying genetic factors in schizophrenia.
METHODS: A cohort of 103 individuals with diagnosed schizophrenia and 110 healthy controls underwent resting-state functional MRI scans. Spontaneous brain activity was assessed using the regional homogeneity (ReHo) metric at four spatial scales: voxel-level (Scale 1) and regional-level (Scales 2-4: 272, 53, 17 regions, respectively). For each spatial scale, multivariate pattern analysis was performed to classify schizophrenia patients from healthy controls, and a transcriptome-neuroimaging association analysis was performed to establish connections between gene expression data and ReHo alterations in schizophrenia.
RESULTS: The ReHo metrics at all spatial scales effectively discriminated schizophrenia from healthy controls. Scale 2 showed the highest classification accuracy at 84.6%, followed by Scale 1 (83.1%) and Scale 3 (78.5%), while Scale 4 exhibited the lowest accuracy (74.2%). Furthermore, the transcriptome-neuroimaging association analysis showed that there were not only shared but also unique enriched biological processes across the four spatial scales. These related biological processes were mainly linked to immune responses, inflammation, synaptic signaling, ion channels, cellular development, myelination, and transporter activity.
CONCLUSIONS: This
study highlights the potential of multi-scale ReHo as a valuable neuroimaging biomarker in the diagnosis of schizophrenia. By elucidating the complex molecular basis underlying the ReHo alterations of this disorder, this
study not only enhances our understanding of its pathophysiology, but also pave the way for future advancements in genetic diagnosis and treatment of schizophrenia.