Elevated Level of Blood Lysosphingolipids in Patients with Schizophrenia

A. E. Kopytova; Копытова А. Э.; N. G. Neznanov; Незнанов Н. Г.; N. M. Zalutskaya; Залуцкая Н. М.; E. Yu. Zakharova; Захарова Е. Ю.; E. I. Palchikova; Пальчикова Е. И.; G. V. Baydakova; Байдакова Г. В.; A. D. Manakhov; Манахов А. Д.; E. V. Volkova; Волкова Е. В.; T. V. Andreeva; Андреева Т. В.; K. S. Basharova; Башарова К. С.; A. I. Bezrukova; Безрукова А. И.; T. S. Usenko; Усенко Т. С.; S. N. Pchelina; Пчелина С. Н.

doi:10.31857/S0016675823060085

Elevated Level of Blood Lysosphingolipids in Patients with Schizophrenia

Authors: Kopytova A.E.¹^,2, Neznanov N.G.¹^,3, Zalutskaya N.M.³, Zakharova E.Y.⁴, Palchikova E.I.³, Baydakova G.V.⁴, Manakhov A.D.⁵^,6^,7, Volkova E.V.¹, Andreeva T.V.⁵^,6^,7, Basharova K.S.², Bezrukova A.I.², Usenko T.S.¹^,2, Pchelina S.N.¹^,2
Affiliations:
1. Pavlov First Saint-Petersburg State Medical University
2. Konstantinov Petersburg Nuclear Physics Institute of National Research Centre “Kurchatov Institute”
3. Bekhterev National Medical Research Center Psychiatry and Neurology
4. Research Center for Medical Genetics
5. Vavilov Institute of General Genetics Russian Academy of Sciences
6. Center of Genetics and Genetic Technologies, Lomonosov Moscow State University
7. Sirius University of Science and Technology
Issue: Vol 59, No 6 (2023)
Pages: 670-675
Section: ГЕНЕТИКА ЧЕЛОВЕКА
URL: https://journals.rcsi.science/0016-6758/article/view/134607
DOI: https://doi.org/10.31857/S0016675823060085
EDN: https://elibrary.ru/SSPQEG
ID: 134607

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Abstract
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Abstract

Schizophrenia is a mental disorder with a prevalence of 0.7–1% of the general population and is characterized by impaired dopamine transmission in neurons. Recent data have shown that lysosomal storage disorders (LSD), characterized by a decrease in enzyme activity and a corresponding accumulation of substrate in lysosomes due to mutations in lysosomal genes, can manifest a wide range of clinical symptoms including psychosis, affective disorders, early onset dementia and schizophrenia. The purpose of this study was to assess the level of lysosphingolipids in patients with schizophrenia, Parkinson’s disease (PD) and control. The study included 52 patients with schizophrenia, 170 patients with PD patients and 166 neurologically healthy individuals (control group). Concentration of lysosomal substrates (hexosylsphingosine (HexSph), globotriaosylsphingosine (LysoGb3), lysosphingomyelin (LysoSM)) were measured by high-liquid chromatography with tandem mass spectrometry (HPLC-MS/MS) in blood. An increase in the concentration of LysoSM, LysoGb3, HexSph was detected in patients with schizophrenia compared to control (p < 0.0001, p < 0.0001, p < 0.0001, respectively). Our results confirm a violation of the lysosphingolipid composition of the blood in patients with schizophrenia.

Keywords

schizophrenia, lysosphingolipids, HPLC-MS/MS, blood.

References

Howrigan D.P., Rose S.A., Samocha K.E. et al. Exome sequencing in schizophrenia-affected parent–offspring trios reveals risk conferred by protein-coding de novo mutations // Nat. Neurosci. 2020. V. 23. P. 185–193. https://doi.org/10.1038/s41593-019-0564-3
Oh J., Shen G., Nan G. et al. Comorbid schizophrenia and Parkinson’s disease: A case series and brief review // Neurol. Asia. 2017. V. 22. P. 139–142.
Papanastasiou E. The prevalence and mechanisms of metabolic syndrome in schizophrenia: a review // Theor. Adv. Psychopharmacol. 2013. V. 3. № 1. P. 33–51. https://doi.org/10.1177/2045125312464385
Castillo R.I., Rojo L.E., Henriquez-Henriquez M. et al. From molecules to the clinic: Linking schizophrenia and metabolic syndrome through sphingolipids metabolism // Front. Neurosci. 2016. V. 10. P. 488–503. https://doi.org/10.3389/fnins.2016.00488
Pardiñas A.F., Holmans P., Pocklington A.J. et al. Common schizophrenia alleles are enriched in mutation-intolerant genes and in regions under strong background selection // Nat. Genet. 2018. V. 50. P. 381–389.
Trakadis Y.J., Fulginiti V., Walterfang M. Inborn errors of metabolism associated with psychosis: Literature review and case-control study using exome data from 5090 adult individuals // J. Inherit. Metab. Dis. 2018. V. 41. № 4. P. 613–621. https://doi.org/10.1007/s10545-017-0023-9
Emelyanov A.K., Usenko T.S., Tesson C. et al. Mutation analysis of Parkinson’s disease genes in a Russian data set // Neurobiol. Aging. 2018. V. 71. P. 267.e7–267.e10. https://doi.org/10.1016/j.neurobiolaging.2018.06.027
Polo G., Burlina A.P., Ranieri E. et al. Plasma and dried blood spot lysosphingolipids for the diagnosis of different sphingolipidoses: a comparative study // Clin. Chem. Lab. Med. 2019. V. 57. № 12. P. 1863–1874.
Czubowicz K., Jęśko H., Wencel P. et al. The role of ceramide and sphingosine-1-phosphate in Alzheimer’s disease and other neurodegenerative disorders // Mol. Neurobiol. 2019. V. 56. P. 5436–5455.
Tkachev A.I., Stekolshchikova E.A., Morozova A.Y. et al. Ceramides: Shared lipid biomarkers of cardiovascular disease and schizophrenia // Consort. Psychiatr. 2021. V. 2. P. 35–43. https://doi.org/10.17816/CP101
Cox T.M. Lysosomal diseases and neuropsychiatry: Opportunities to rebalance the mind // Front. Mol. Biosci. 2020. V. 7. P. 177–185. https://doi.org/10.3389/fmolb.2020.00177
Sidransky E., Nalls M.A., Aasly J.O. et al. Multi-center analysis of glucocerebrosidase mutations in Parkinson disease // N. Engl. J. Med. 2009. V. 361. P. 1651–1661. https://doi.org/10.1056/NEJMOA0901281
Kopytova A.E., Usenko T.S., Baydakova G.V. et al. Could blood hexosylsphingosinebe a marker for Parkinson’s disease linked with GBA1 mutations? // Mov. Disord. 2022. V. 37. № 8. P. 1779–1781. https://doi.org/10.1002/mds.29132
Moors T.E., Paciotti S., Ingrassia A. et al. Characterization of brain lysosomal activities in GBA-related and sporadic Parkinson’s disease and dementia with Lewybodies // Mol. Neurobiol. 2019. V. 56. P. 1344–1355.
Usenko T.S., Senkevich K.A., Bezrukova A.I. et al. Impaired sphingolipid hydrolase activities in dementia with Lewybodies and multiple system atrophy // Mol. Neurobiol. 2022. V. 59. P. 2277–2787.
Kuusimäki T., Al-Abdulrasul H., Kurki S. et al. Increased risk of Parkinson’s disease in patients with schizophrenia spectrum disorders // Mov. Disord. 2021. V. 36. P. 1353–1361.
De Vries P.J., Honer W.G., Kemp P.M., McKenna P.J. Dementia as a complication of schizophrenia // J. Neurol. Neurosurg. Psychiatry. 2001. V. 70. P. 588–596.
Komatsu H., Kato M., Kinpara T. et al. Possible multiple system atrophy with predominant parkinsonism in a patient with chronic schizophrenia: A case report // BMC Psychiatry. 2018. V. 18. P. 1–9.
Schwarz E., Prabakaran S., Whitfield P. et al. High throughput lipidomic profiling of schizophrenia and bipolar disorder brain tissue reveals alterations of free fatty acids, phosphatidylcholines, and ceramides // J. Proteome Res. 2008. V. 7. P. 4266–4277.
Wood P.L. Targeted lipidomics and metabolomics evaluations of cortical neuronal stress in schizophrenia // Schizophr. Res. 2019. V. 212. P. 107–112.
Tessier C., Sweers K., Frajerman A. et al. Membrane lipidomics in schizophrenia patients: A correlational study with clinical and cognitive manifestations // Transl. Psychiatry. 2016. V. 6. P. e906–e914.
Paciotti S., Albi E., Parnetti L., Beccari T. Lysosomal ceramide metabolism disorders: Implications in Parkinson’s disease // J. Clin. Med. 2020. V. 9. P. 594–614.
Takahashi N., Sakurai T., Davis K.L., Buxbaum J.D. Linking oligodendrocyte and myelin dysfunction to neurocircuitry abnormalities in schizophrenia // Prog. Neurobiol. 2011. V. 93. P. 13–24.
Vallée A. Neuroinflammation in schizophrenia: The key role of the WNT/β-catenin pathway // Int. J. Mol. Sci. 2022. V. 23. P. 2810–2825.
Gouvêa-Junqueira D., Falvella A.C.B., Antunes A.S.L.M. et al. Novel treatment strategies targeting myelin and oligodendrocytedysfunction inschizophrenia // Front. Psychiatry. 2020. V. 11. P. 379–395.
Mihaylova V., Hantke J., Sinigerska I. et al. Highly variable neural involvement in sphingomyelinase-deficient Niemann–Pick disease caused by an ancestral Gypsy mutation // Brain. 2007. V. 130. P. 1050–1061. https://doi.org/10.1093/brain/awm026
Zhuo C., Zhao F., Tian H. et al. Acid sphingomyelinase/ceramide system in schizophrenia: Implications for therapeutic intervention as a potential novel target // Transl. Psychiatry. 2022. V. 12. P. 260–266. https://doi.org/10.1038/s41398-022-01999-7
Akhtar M.M., Elliott P.M. Anderson–Fabry disease in heart failure // Biophys. Rev. 2018. V. 10. P. 1107–1119.
Usenko T.S., Bezrukova A.I., Basharova K.S. et al. Link between schizophrenia and lysosomal storage disorders based on NGS and LC-MS/MS analyses // Am. J. Geriatr. Psychiatry. 2023. Submitted to journal.

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Elevated Level of Blood Lysosphingolipids in Patients with Schizophrenia

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Abstract

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About the authors

References

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