Profiling of Lipidomics Before and After Antipsychotic Treatment in First-Episode Psychosis

Abstract

Alterations in complex lipids may be involved in pathophysiology of schizophrenia spectrum disorders. In our previous study, we demonstrated importance of detecting lipid metabolism dysregulation by acylcarnitine (ACs) profile analysis in patients with first-episode psychosis (FEP). Here we adopt lipidomics to identify serum glycerophospholipids (GPLs), and sphingomyelins (SMs) for describing FEP status before and after 7 months antipsychotic treatment. Using mass spectrometry and liquid chromatography technique, we profiled 105 individual lipids [14 lysophosphatidylcholines (lysoPCs), 76 phosphatidylcholines (PCs), and 15 sphingomyelins (SMs)] in serum samples from 53 antipsychotic-naive 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-naive FEP patients when compared to CSs. Comparison of serum lipids profiles of FEP patients before and after 7-month antipsychotic treatment revealed that 11 GPLs (2 Lyso-PCs, 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 lipids profile abnormalities are specifically associated with FEP and these discrepancies reflect two different disease-related pathways. Our findings also 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. Funding Statement: This research was supported by the European Union through the European Regional Development Fund (Project No. 2014-2020.4.01.15-0012), and grants from the Estonian Research Foundation (IUT 20-41, IUT 20-42) Declaration of Interests: There are no relevant conflict of interest from any of the authors. Ethics Approval Statement: All subjects gave written informed consent in accordance with the Declaration of Helsinki. The protocol was approved by the Ethics Review Committee on Human Research of the University of Tartu (Estonia).