Jaskiw George E, Obrenovich Mark E, Donskey Curtis J, Briggs Farren B S, Chung Sun Sunnie, Kalinina Anastasiya I, Bolomey Austin, Hayes Lindsay N, Yang Kun, Yolken Robert H, Sawa Akira
Veterans Affairs Northeast Ohio Healthcare System, Cleveland, OH 44106, USA.
School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.
Metabolites. 2025 Apr 15;15(4):275. doi: 10.3390/metabo15040275.
(1) Background: The lack of reliable biomarkers remains a significant barrier to improving outcomes for patients with schizophrenia. While metabolomic analyses of blood, urine, and feces have been explored, results have been inconsistent. Compared to peripheral compartments, cerebrospinal fluid (CSF) more closely reflects the chemical composition of brain extracellular fluid. Given that brain dysregulation may be more pronounced during the first episode of psychosis (FEP), we hypothesized that metabolomic analysis of CSF from FEP patients could reveal disease-associated biomarkers. (2) Methods: We recruited 15 patients within 24 months of psychosis onset (DSM-4 criteria) and 14 control participants through the Johns Hopkins Schizophrenia Center. CSF samples were analyzed using both non-targeted and targeted liquid chromatography-mass spectrometry. (3) Results: The non-targeted analysis identified lower levels of N-acetylneuraminic acid and N-acetyl-L-aspartic acid in the FEP group, while levels of uric acid were elevated. The targeted analysis focused on indolic and phenolic molecules previously linked to neuropsychiatric disorders. Notably, L-phenylalanine and 4-hydroxycinnamic acid levels were lower in the FEP group, and this difference remained significant after adjusting for age and sex. However, none of the significant differences in analyte levels between the groups survived an adjustment for multiple comparisons. (4) Conclusions: Our intriguing but preliminary associations align with results from other investigational approaches and highlight potential CSF analytes that warrant further study in larger samples.
(1) 背景：缺乏可靠的生物标志物仍然是改善精神分裂症患者预后的重大障碍。虽然已经对血液、尿液和粪便进行了代谢组学分析，但结果并不一致。与外周腔室相比，脑脊液（CSF）更能反映脑细胞外液的化学成分。鉴于在精神病首次发作（FEP）期间脑功能失调可能更为明显，我们假设对FEP患者的脑脊液进行代谢组学分析可以揭示与疾病相关的生物标志物。(2) 方法：我们通过约翰霍普金斯精神分裂症中心招募了15名在精神病发作（符合DSM-4标准）24个月内的患者和14名对照参与者。使用非靶向和靶向液相色谱-质谱联用技术分析脑脊液样本。(3) 结果：非靶向分析发现FEP组中N-乙酰神经氨酸和N-乙酰-L-天冬氨酸水平较低，而尿酸水平升高。靶向分析集中在先前与神经精神疾病相关的吲哚和酚类分子上。值得注意的是，FEP组中L-苯丙氨酸和4-羟基肉桂酸水平较低，在调整年龄和性别后，这种差异仍然显著。然而，在对多重比较进行调整后，两组间分析物水平的显著差异均未留存。(4) 结论：我们有趣但初步的关联与其他研究方法的结果一致，并突出了潜在的脑脊液分析物，这些分析物值得在更大样本中进一步研究。
