Center for Neuropsychiatric Schizophrenia Research and Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research, Mental Health Centre Glostrup, Copenhagen University Hospital, Nordstjernevej 41, 2600, Glostrup, Denmark.
Functional Imaging Unit, Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet, Glostrup, Denmark.
Eur Arch Psychiatry Clin Neurosci. 2023 Dec;273(8):1797-1812. doi: 10.1007/s00406-023-01598-7. Epub 2023 Apr 4.
Multiple lines of research support the dysconnectivity hypothesis of schizophrenia. However, findings on white matter (WM) alterations in patients with schizophrenia are widespread and non-specific. Confounding factors from magnetic resonance image (MRI) processing, clinical diversity, antipsychotic exposure, and substance use may underlie some of the variability. By application of refined methodology and careful sampling, we rectified common confounders investigating WM and symptom correlates in a sample of strictly antipsychotic-naïve first-episode patients with schizophrenia. Eighty-six patients and 112 matched controls underwent diffusion MRI. Using fixel-based analysis (FBA), we extracted fibre-specific measures such as fibre density and fibre-bundle cross-section. Group differences on fixel-wise measures were examined with multivariate general linear modelling. Psychopathology was assessed with the Positive and Negative Syndrome Scale. We separately tested multivariate correlations between fixel-wise measures and predefined psychosis-specific versus anxio-depressive symptoms. Results were corrected for multiple comparisons. Patients displayed reduced fibre density in the body of corpus callosum and in the middle cerebellar peduncle. Fibre density and fibre-bundle cross-section of the corticospinal tract were positively correlated with suspiciousness/persecution, and negatively correlated with delusions. Fibre-bundle cross-section of isthmus of corpus callosum and hallucinatory behaviour were negatively correlated. Fibre density and fibre-bundle cross-section of genu and splenium of corpus callosum were negative correlated with anxio-depressive symptoms. FBA revealed fibre-specific properties of WM abnormalities in patients and differentiated associations between WM and psychosis-specific versus anxio-depressive symptoms. Our findings encourage an itemised approach to investigate the relationship between WM microstructure and clinical symptoms in patients with schizophrenia.
多项研究支持精神分裂症的连接断开假说。然而，精神分裂症患者的脑白质（WM）改变的发现广泛而不具体。磁共振成像（MRI）处理、临床多样性、抗精神病药物暴露和物质使用的混杂因素可能是导致这种变异性的部分原因。通过应用精细的方法和仔细的采样，我们纠正了常见的混杂因素，在一组严格的抗精神病药物初发的精神分裂症患者中研究 WM 和症状相关性。86 名患者和 112 名匹配的对照者接受了弥散张量成像（DTI）检查。使用基于纤维束的分析（FBA），我们提取了纤维特异性指标，如纤维密度和纤维束横截面积。采用多元线性模型对纤维束的固定点测量进行了组间差异检验。使用阳性和阴性症状量表评估精神病理学。我们分别测试了固定点测量与预先定义的精神病特异性与焦虑抑郁症状之间的多元相关性。结果经过了多重比较校正。患者的胼胝体体部和小脑中脚的纤维密度降低。皮质脊髓束的纤维密度和纤维束横截面积与猜疑/迫害呈正相关，与妄想呈负相关。胼胝体峡部和幻觉行为与纤维束横截面积呈负相关。胼胝体膝部和压部的纤维密度和纤维束横截面积与焦虑抑郁症状呈负相关。FBA 揭示了患者 WM 异常的纤维特异性特征，并区分了 WM 与精神病特异性与焦虑抑郁症状之间的关联。我们的发现鼓励采用逐项方法研究精神分裂症患者 WM 微观结构与临床症状之间的关系。
