Department of Psychiatry and Psychotherapy, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Clinic of Neurology and Neurophysiology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Schizophr Bull. 2023 Mar 15;49(2):464-473. doi: 10.1093/schbul/sbac135.
Schizophrenia spectrum disorders (SSD) can be associated with neurodegenerative processes causing disruption of neuronal, synaptic, or axonal integrity. Some previous studies have reported alterations of neurodegenerative markers (such as amyloid beta [Aβ], tau, or neurofilaments) in patients with SSD. However, the current state of research remains inconclusive. Therefore, the rationale of this study was to investigate established neurodegenerative markers in the cerebrospinal fluid (CSF) of a large group of patients with SSD.
Measurements of Aβ1-40, Aß1-42, phospho- and total-tau in addition to neurofilament light (NFL), medium (NFM), and heavy (NFH) chains were performed in the CSF of 100 patients with SSD (60 F, 40 M; age 33.7 ± 12.0) and 39 controls with idiopathic intracranial hypertension (33 F, 6 M; age 34.6 ± 12.0) using enzyme-linked immunoassays.
The NFM levels were significantly increased in SSD patients (P = .009), whereas phospho-tau levels were lower in comparison to the control group (P = .018). No other significant differences in total-tau, beta-amyloid-quotient (Aβ1-42/Aβ1-40), NFL, and NFH were identified.
The findings argue against a general tauopathy or amyloid pathology in patients with SSD. However, high levels of NFM, which has been linked to regulatory functions in dopaminergic neurotransmission, were associated with SSD. Therefore, NFM could be a promising candidate for further research on SSD.
精神分裂症谱系障碍（SSD）可能与导致神经元、突触或轴突完整性破坏的神经退行性过程有关。一些先前的研究报告称，SSD 患者存在神经退行性标志物（如β淀粉样蛋白 [Aβ]、tau 或神经丝）的改变。然而，目前的研究状况仍不确定。因此，本研究的目的是在一大群 SSD 患者的脑脊液（CSF）中研究已建立的神经退行性标志物。
使用酶联免疫吸附试验在 100 名 SSD 患者（60 名女性，40 名男性；年龄 33.7 ± 12.0）和 39 名特发性颅内高压对照者（33 名女性，6 名男性；年龄 34.6 ± 12.0）的 CSF 中测量 Aβ1-40、Aβ1-42、磷酸化和总 tau 以及神经丝轻（NFL）、中（NFM）和重（NFH）链。
SSD 患者的 NFM 水平显著升高（P =.009），而与对照组相比，磷酸化 tau 水平较低（P =.018）。总 tau、β-淀粉样蛋白比值（Aβ1-42/Aβ1-40）、NFL 和 NFH 没有其他显著差异。
这些发现表明 SSD 患者不存在普遍的 tau 病或淀粉样蛋白病理学。然而，与多巴胺能神经递质的调节功能相关的 NFM 水平升高与 SSD 相关。因此，NFM 可能是 SSD 进一步研究的有前途的候选标志物。
