Cilia Brandon-Joe, Eratne Dhamidhu, Wannan Cassandra, Malpas Charles, Janelidze Shorena, Hansson Oskar, Everall Ian, Bousman Chad, Thomas Naveen, Santillo Alexander F, Velakoulis Dennis, Pantelis Christos
Neuropsychiatry, The Royal Melbourne Hospital, Parkville, VIC, Australia.
Melbourne Medical School, The University of Melbourne, Parkville, VIC, Australia.
Aust N Z J Psychiatry. 2025 Mar;59(3):248-259. doi: 10.1177/00048674241307906. Epub 2025 Jan 4.
Around 30% of people with schizophrenia are refractory to antipsychotic treatment (treatment-resistant schizophrenia). Abnormal structural neuroimaging findings, in particular volume and thickness reductions, are often described in schizophrenia. Novel biomarkers of active brain pathology such as neurofilament light chain protein are now expected to improve current understanding of psychiatric disorders, including schizophrenia. This study explored whether treatment-resistant schizophrenia individuals exhibit different associations between plasma neurofilament light chain protein levels and regional cortical thickness reductions compared with controls.
Plasma neurofilament light chain protein levels were measured, and T1-weighted magnetic resonance imaging sequences were obtained and processed via FreeSurfer for each participant. General linear models adjusting for age and body mass index were estimated to determine whether the interaction between diagnostic group and plasma neurofilament light chain protein level predicted lower cortical thickness across frontotemporal structures and the insula.
A total of 79 participants were included: 37 treatment-resistant schizophrenia and 42 healthy controls. Significant (false discovery rate-corrected) cortical thinning of the left ( = 0.005, = 0.100) and right ( = 0.002, = 0.149) insula, and left inferior temporal gyrus ( < 0.001, = 0.143) was associated with higher levels of plasma neurofilament light chain protein in treatment-resistant schizophrenia, but not in healthy controls.
The association between regional thickness reduction of the bilateral insula and left inferior temporal gyrus with plasma neurofilament light chain protein may reflect a neuroprogressive component to schizophrenia, which is not observed in the normal population.
约30%的精神分裂症患者对抗精神病药物治疗无效（难治性精神分裂症）。精神分裂症患者常出现异常的结构性神经影像学表现，尤其是脑容量和厚度的减少。诸如神经丝轻链蛋白等活跃脑病理的新型生物标志物有望改善目前对包括精神分裂症在内的精神疾病的理解。本研究探讨了难治性精神分裂症患者与对照组相比，血浆神经丝轻链蛋白水平与区域皮质厚度减少之间是否存在不同的关联。
测量每位参与者的血浆神经丝轻链蛋白水平，并通过FreeSurfer获得并处理T1加权磁共振成像序列。估计调整年龄和体重指数的一般线性模型，以确定诊断组与血浆神经丝轻链蛋白水平之间的相互作用是否能预测额颞叶结构和脑岛的皮质厚度降低。
共纳入79名参与者：37名难治性精神分裂症患者和42名健康对照者。难治性精神分裂症患者左侧脑岛（P = 0.005，效应量 = 0.100）、右侧脑岛（P = 0.002，效应量 = 0.149）和左侧颞下回（P < 0.001，效应量 = 0.143）的显著（经错误发现率校正）皮质变薄与血浆神经丝轻链蛋白水平升高相关，但在健康对照者中未观察到这种关联。
双侧脑岛和左侧颞下回区域厚度减少与血浆神经丝轻链蛋白之间的关联可能反映了精神分裂症的神经进行性成分，而在正常人群中未观察到这种情况。
