Palaniyappan Lena, Marques Tiago Reis, Taylor Heather, Mondelli Valeria, Reinders A A T Simone, Bonaccorso Stefania, Giordano Annalisa, DiForti Marta, Simmons Andrew, David Anthony S, Pariante Carmine M, Murray Robin M, Dazzan Paola
Departments of Psychiatry, Neuroscience and Medical Biophysics & Robarts Research Institute, Western University, London, ON, Canada.
Lawson Health Research Institute, London, ON, Canada.
Schizophr Bull. 2016 Nov;42(6):1446-1456. doi: 10.1093/schbul/sbw069. Epub 2016 Jun 28.
Converging evidence suggests that patients with first-episode psychosis who show a poor treatment response may have a higher degree of neurodevelopmental abnormalities than good Responders. Characterizing the disturbances in the relationship among brain regions (covariance) can provide more information on neurodevelopmental integrity than searching for localized changes in the brain. Graph-based connectomic approach can measure structural covariance thus providing information on the maturational processes. We quantified the structural covariance of cortical folding using graph theory in first-episode psychosis, to investigate if this systems-level approach would improve our understanding of the biological determinants of outcome in psychosis.
Magnetic Resonance Imaging data were acquired in 80 first-episode psychosis patients and 46 healthy controls. Response to treatment was assessed after 12 weeks of naturalistic follow-up. Gyrification-based connectomes were constructed to study the maturational organization of cortical folding.
Nonresponders showed a reduction in the distributed relationship among brain regions (high segregation, poor integration) when compared to Responders and controls, indicating a higher burden of aberrant neurodevelopment. They also showed reduced centrality of key regions (left insula and anterior cingulate cortex) indicating a marked reconfiguration of gyrification. Nonresponders showed a vulnerable pattern of covariance that disintegrated when simulated lesions removed high-degree hubs, indicating an abnormal dependence on highly central hub regions in Nonresponders.
These findings suggest that a perturbed maturational relationship among brain regions underlies poor treatment response in first-episode psychosis. The information obtained from gyrification-based connectomes can be harnessed for prospectively predicting treatment response and prognosis in psychosis.
越来越多的证据表明，首次发作精神病且治疗反应不佳的患者可能比反应良好的患者有更高程度的神经发育异常。与寻找大脑局部变化相比，描述脑区之间关系（协方差）的紊乱可以提供更多关于神经发育完整性的信息。基于图谱的连接组学方法可以测量结构协方差，从而提供有关成熟过程的信息。我们使用图谱理论对首次发作精神病患者的皮质折叠结构协方差进行量化，以研究这种系统水平的方法是否能增进我们对精神病结局生物学决定因素的理解。
对80例首次发作精神病患者和46例健康对照者进行磁共振成像数据采集。在自然随访12周后评估治疗反应。构建基于脑回的连接组以研究皮质折叠的成熟组织。
与反应良好者和对照组相比，无反应者脑区之间的分布式关系减少（高度分离，整合不良），表明异常神经发育的负担更高。他们还显示关键区域（左侧岛叶和前扣带回皮质）的中心性降低，表明脑回有明显的重新配置。无反应者表现出一种脆弱的协方差模式，当模拟损伤去除高度连接的枢纽时，这种模式瓦解，表明无反应者对高度中心枢纽区域存在异常依赖。
这些发现表明，脑区之间成熟关系的紊乱是首次发作精神病治疗反应不佳的基础。从基于脑回的连接组获得的信息可用于前瞻性预测精神病的治疗反应和预后。
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