Psychiatry Clinic of Tartu University Hospital, 31 Raja Street, 50417, Tartu, Estonia.
Institute of Biomedicine and Translational Medicine, Centre of Excellence for Genomics and Translational Medicine, University of Tartu, 19 Ravila Street, 50411, Tartu, Estonia.
Eur Arch Psychiatry Clin Neurosci. 2020 Feb;270(1):59-70. doi: 10.1007/s00406-018-0971-6. Epub 2019 Jan 2.
Alterations in complex lipids may be involved in pathophysiology of schizophrenia spectrum disorders. Previously, we demonstrated importance of detecting lipid metabolism dysregulation by acylcarnitine (ACs) profile analysis in patients with first-episode psychosis (FEP). The aim of this study was to adopt lipidomics to identify serum glycerophospholipids (GPLs) and sphingomyelins (SMs) for describing FEP status before and after 7-month antipsychotic treatment. Using mass spectrometry and liquid chromatography technique, we profiled 105 individual lipids [14 lysophosphatidylcholines (LysoPCs), 76 phosphatidylcholines (PCs) and 15 SMs] in serum samples from 53 antipsychotic-naïve FEP patients, 44 of them were studied longitudinally and from 37 control subjects (CSs). Among the identified and quantified metabolites one LysoPC was elevated, and contrary the levels of 16 PCs as well as the level of one SM were significantly (p ≤ 0.0005) reduced in antipsychotic-naïve FEP patients compared to CSs. Comparison of serum lipids profiles of FEP patients before and after 7-month antipsychotic treatment revealed that 11 GPLs (2 LysoPCs, 9 PCs), and 2 SMs were found to be significantly changed (p ≤ 0.0005) in which GPLs were up-regulated, and SMs were down-regulated. However, no significant differences were noted when treated patient's serum lipid profiles were compared with CSs. Our findings suggest that complex lipid profile abnormalities are specifically associated with FEP and these discrepancies reflect two different disease-related pathways. Our findings provide insight into lipidomic information that may be used for monitoring FEP status and impact of the treatment in the early stage of the schizophrenia spectrum disorder.
复杂脂质的改变可能与精神分裂症谱系障碍的病理生理学有关。此前,我们证明了在首发精神病患者(FEP)中通过酰基肉碱(AC)谱分析检测脂质代谢失调的重要性。本研究的目的是采用脂质组学来鉴定血清甘油磷脂(GPLs)和神经鞘磷脂(SMs),以描述 FEP 状态在抗精神病药物治疗 7 个月前后的变化。我们使用质谱和液相色谱技术,对 53 名未经抗精神病药物治疗的 FEP 患者、其中 44 名进行了纵向研究和 37 名对照(CSs)的血清样本进行了 105 种个体脂质(14 种溶血磷脂酰胆碱(LysoPCs)、76 种磷脂酰胆碱(PCs)和 15 种 SMs)的分析。在鉴定和定量的代谢物中,一种 LysoPC 升高,相反,未经抗精神病药物治疗的 FEP 患者的 16 种 PCs 水平以及一种 SM 水平均显著(p ≤ 0.0005)低于 CSs。比较 FEP 患者在接受 7 个月抗精神病药物治疗前后的血清脂质谱,发现 11 种 GPLs(2 种 LysoPCs、9 种 PCs)和 2 种 SMs 的变化显著(p ≤ 0.0005),其中 GPLs 上调,SMs 下调。然而,当治疗患者的血清脂质谱与 CSs 进行比较时,没有发现显著差异。我们的研究结果表明,复杂的脂质谱异常与 FEP 特异性相关,这些差异反映了两种不同的与疾病相关的途径。我们的研究结果为脂质组学信息提供了深入了解,这些信息可能用于监测 FEP 状态和精神分裂症谱系障碍早期治疗的影响。