Department of Psychiatry,Melbourne Neuropsychiatry Centre,The University of Melbourne and Melbourne Health,Carlton South, VIC,Australia.
Discipline of Psychiatry,The University of Adelaide,SA,Australia.
Psychol Med. 2017 Dec;47(16):2797-2810. doi: 10.1017/S0033291717001313. Epub 2017 May 22.
White matter disruptions in schizophrenia have been widely reported, but it remains unclear whether these abnormalities differ between illness stages. We mapped the connectome in patients with recently diagnosed and chronic schizophrenia and investigated the extent and overlap of white matter connectivity disruptions between these illness stages.
Diffusion-weighted magnetic resonance images were acquired in recent-onset (n = 19) and chronic patients (n = 45) with schizophrenia, as well as age-matched controls (n = 87). Whole-brain fiber tracking was performed to quantify the strength of white matter connections. Connections were tested for significant streamline count reductions in recent-onset and chronic groups, relative to separate age-matched controls. Permutation tests were used to assess whether disrupted connections significantly overlapped between chronic and recent-onset patients. Linear regression was performed to test whether connectivity was strongest in controls, weakest in chronic patients, and midway between these extremities in recent-onset patients (controls > recent-onset > chronic).
Compared with controls, chronic patients displayed a widespread network of connectivity disruptions (p < 0.01). In contrast, connectivity reductions were circumscribed to the anterior fibers of the corpus callosum in recent-onset patients (p < 0.01). A significant proportion of disrupted connections in recent-onset patients (86%) coincided with disrupted connections in chronic patients (p < 0.01). Linear regression revealed that chronic patients displayed reduced connectivity relative to controls, while recent-onset patients showed an intermediate reduction compared with chronic patients (p < 0.01).
Connectome pathology in recent-onset patients with schizophrenia is confined to select tracts within a more extensive network of white matter connectivity disruptions found in chronic illness. These findings may suggest a trajectory of progressive deterioration of connectivity in schizophrenia.
精神分裂症的白质紊乱已被广泛报道，但目前尚不清楚这些异常是否在疾病阶段有所不同。我们对初诊和慢性精神分裂症患者进行了连接组学研究，并调查了这些疾病阶段之间白质连接中断的程度和重叠。
对近期发病（n=19）和慢性（n=45）精神分裂症患者以及年龄匹配的对照组（n=87）进行了弥散加权磁共振成像采集。全脑纤维追踪用于量化白质连接的强度。在近期发病和慢性组中，对连接体进行测试，以确定与单独的年龄匹配对照组相比，有多少连接体的流线计数减少。使用置换检验评估慢性和近期发病患者之间的破坏连接是否显著重叠。进行线性回归以测试连接是否在对照组中最强，在慢性患者中最弱，并且在近期发病患者中处于这两个极端之间（对照组>近期发病>慢性）。
与对照组相比，慢性患者表现出广泛的连接中断网络（p<0.01）。相比之下，近期发病患者的连接体减少仅限于胼胝体的前部纤维（p<0.01）。近期发病患者中有相当比例的破坏连接（86%）与慢性患者的破坏连接重合（p<0.01）。线性回归显示，慢性患者的连接体相对于对照组减少，而近期发病患者的连接体相对于慢性患者减少（p<0.01）。
精神分裂症初诊患者的连接组病理学局限于慢性疾病中更广泛的白质连接中断网络内的特定束。这些发现可能表明精神分裂症患者的连接体恶化存在进行性轨迹。
