The Zurich Program for Sustainable Development of Mental Health Services (ZInEP), Psychiatric University Hospital Zurich, University of Zurich, Zurich, Switzerland; Department of Child and Adolescent Psychiatry and Psychotherapy, Psychiatric University Hospital Zurich, University of Zurich, Zurich, Switzerland.
Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric University Hospital Zurich, University of Zurich, Zurich, Switzerland; MR-Center of the Psychiatric Hospital and the Department of Child and Adolescent Psychiatry, University of Zurich, Zurich, Switzerland.
Neuroimage Clin. 2022;35:103067. doi: 10.1016/j.nicl.2022.103067. Epub 2022 May 31.
Widespread white matter abnormalities are a frequent finding in chronic schizophrenia patients. More inconsistent results have been provided by the sparser literature on at-risk states for psychosis, i.e., emerging subclinical symptoms. However, considering risk as a homogenous construct, an approach of earlier studies, may impede our understanding of neuro-progression into psychosis.
An analysis was conducted of 3-Tesla MRI diffusion and symptom data from 112 individuals (mean age, 21.97 ± 4.19) within two at-risk paradigm subtypes, only basic symptoms (n = 43) and ultra-high risk (n = 37), and controls (n = 32). Between-group comparisons (involving three study groups and further split based on the subsequent transition to schizophrenia) of four diffusion-tensor-imaging-derived scalars were performed using voxelwise tract-based spatial statistics, followed by correlational analyses with Structured Interview for Prodromal Syndromes responses.
Relative to controls, fractional anisotropy was lower in the splenium of the corpus callosum of ultra-high-risk individuals, but only before stringent multiple-testing correction, and negatively correlated with General Symptom severity among at-risk individuals. At-risk participants who transitioned to schizophrenia within 3 years, compared to those that did not transition, had more severe WM differences in fractional anisotropy and radial diffusivity (particularly in the corpus callosum, anterior corona radiata, and motor/sensory tracts), which were even more extensive compared to healthy controls.
These findings align with the subclinical symptom presentation and more extensive disruptions in converters, suggestive of severity-related demyelination or axonal pathology. Fine-grained but detectable differences among ultra-high-risk subjects (i.e., with brief limited intermittent and/or attenuated psychotic symptoms) point to the splenium as a discrete site of emerging psychopathology, while basic symptoms alone were not associated with altered fractional anisotropy.
广泛的白质异常是慢性精神分裂症患者的常见发现。在精神病风险较低的状态（即出现亚临床症状）的研究中，文献报道的结果更为不一致。然而，考虑到风险是一个同质的结构，早期研究的方法可能会阻碍我们对精神病神经进展的理解。
对来自两个风险范式亚型（仅基本症状亚组[ n = 43]和超高风险亚组[ n = 37]）和对照组（ n = 32）的 112 名个体（平均年龄 21.97 ± 4.19）的 3-Tesla MRI 扩散和症状数据进行了分析。使用基于体素的束空间统计对四个扩散张量成像衍生标量进行了组间比较（涉及三个研究组，并进一步根据随后向精神分裂症的转变进行了细分），然后与结构访谈前驱综合征反应进行了相关性分析。
与对照组相比，超高风险个体的胼胝体压部的各向异性分数较低，但仅在前严格的多重检验校正后，且与风险个体的一般症状严重程度呈负相关。在 3 年内向精神分裂症转变的风险参与者与未转变的参与者相比，在各向异性分数和径向弥散度方面存在更严重的 WM 差异（特别是在胼胝体、前冠状辐射和运动/感觉束），与健康对照组相比，差异更为广泛。
这些发现与亚临床症状表现一致，且在转换者中更为广泛的破坏，提示与严重程度相关的脱髓鞘或轴突病理学。超高风险受试者之间存在细微但可检测的差异（即短暂的有限间歇性和/或减轻的精神病症状），表明胼胝体是一个新出现的精神病理学离散部位，而单独的基本症状与各向异性分数改变无关。
