Sierra Pacific Mental Illness Research Education and Clinical Centers, San Francisco VA Medical Center and the University of California, San Francisco, CA, USA; San Francisco VA Medical Center, San Francisco, CA 94121, USA; Department of Psychiatry and Behavioral Sciences, University of California San Francisco, San Francisco, CA 94143, USA; Department of Psychological Sciences, University of Missouri, Columbia, MO 65211, USA.
Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA 94143, USA; Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA 94143, USA.
Schizophr Res. 2023 May;255:110-121. doi: 10.1016/j.schres.2023.03.016. Epub 2023 Mar 27.
Brain dysconnectivity has been posited as a biological marker of schizophrenia. Emerging schizophrenia connectome research has focused on rich-club organization, a tendency for brain hubs to be highly-interconnected but disproportionately vulnerable to dysconnectivity. However, less is known about rich-club organization in individuals at clinical high-risk for psychosis (CHR-P) and how it compares with abnormalities early in schizophrenia (ESZ). Combining diffusion tensor imaging (DTI) and magnetic resonance imaging (MRI), we examined rich-club and global network organization in CHR-P (n = 41) and ESZ (n = 70) relative to healthy controls (HC; n = 74) after accounting for normal aging. To characterize rich-club regions, we examined rich-club MRI morphometry (thickness, surface area). We also examined connectome metric associations with symptom severity, antipsychotic dosage, and in CHR-P specifically, transition to a full-blown psychotic disorder. ESZ had fewer connections among rich-club regions (ps < .024) relative to HC and CHR-P, with this reduction specific to the rich-club even after accounting for other connections in ESZ relative to HC (ps < .048). There was also cortical thinning of rich-club regions in ESZ (ps < .013). In contrast, there was no strong evidence of global network organization differences among the three groups. Although connectome abnormalities were not present in CHR-P overall, CHR-P converters to psychosis (n = 9) had fewer connections among rich-club regions (ps < .037) and greater modularity (ps < .037) compared to CHR-P non-converters (n = 19). Lastly, symptom severity and antipsychotic dosage were not significantly associated with connectome metrics (ps < .012). Findings suggest that rich-club and connectome organization abnormalities are present early in schizophrenia and in CHR-P individuals who subsequently transition to psychosis.
脑连接异常被认为是精神分裂症的生物学标志物。新兴的精神分裂症连接组学研究集中于丰富俱乐部组织，即大脑枢纽高度连接但不成比例地容易出现连接异常的趋势。然而，对于处于精神病临床高风险（CHR-P）的个体中的丰富俱乐部组织及其与精神分裂症早期（ESZ）的异常情况相比，人们知之甚少。本研究结合弥散张量成像（DTI）和磁共振成像（MRI），在考虑正常衰老的情况下，比较了 CHR-P（n=41）和 ESZ（n=70）与健康对照组（HC；n=74）的丰富俱乐部和全局网络组织。为了描述丰富俱乐部区域，我们检查了丰富俱乐部 MRI 形态测量学（厚度、表面积）。我们还检查了连接组学指标与症状严重程度、抗精神病药物剂量的关联，特别是在 CHR-P 中，检查了与发展为全面精神病障碍的关联。与 HC 和 CHR-P 相比，ESZ 中丰富俱乐部区域之间的连接较少（ps<0.024），这一减少在 ESZ 中相对于 HC 的其他连接（ps<0.048）也具有特异性。ESZ 中丰富俱乐部区域的皮质也变薄（ps<0.013）。相比之下，三组之间没有明显的全局网络组织差异的证据。尽管 CHR-P 总体上没有连接组异常，但发展为精神病的 CHR-P 转换者（n=9）与 CHR-P 非转换者（n=19）相比，丰富俱乐部区域之间的连接较少（ps<0.037），模块性更大（ps<0.037）。最后，症状严重程度和抗精神病药物剂量与连接组学指标没有显著关联（ps<0.012）。研究结果表明，丰富俱乐部和连接组组织异常在精神分裂症和随后发展为精神病的 CHR-P 个体中很早就存在。
