Category: Neurophysiology (Non-PD)
Objective: To estimate whether alteration of lysosomal activities contributes to schizophrenia (SCZ) pathogenesis, age at onset and risk of developing the disease.
Background: SCZ is a mental disorder. Last data demonstrated that lysosomal storage disorders (LSDs) accompanied by a decrease of enzyme activity and corresponding substrate accumulation in lysosomes may manifest with a wide spectrum of clinical presentations including psychosis, mood disorders and SCZ [1].
Method: 42 SCZ patients and 176 controls were enrolled. Lysosomal enzyme activities (glucoceresobridase (GCase), alpha-galactosidase (GLA), acid sphingomyelinase (ASMase), galactosylceramidase (GALC), alpha-L-iduronidase (IDUA), acid alpha-glucosidase (GAA)) and concentration of lysosomal substrates (hexosylsphingosine (HexSph), globotriaosylsphingosine (LysoGb3), lysosphingomyelin (LysoSM)) were measured by LC-MS/MS in blood.
Results: Decreased ASMase activity was found in SCZ patients compared to controls (p<0.0001) with increase of its substrate concentration, LysoSM, in SCZ patients compared to controls (p=0.0002). Higher LysoSM concentration was associated with increased risk of SCZ (OR=1.44, p=0.02) and higher ASMase activity was associated with decreased risk of SCZ (OR=0.47, p=0.0002). HexSph concentration was increased in SCZ patients compared to controls (p<0.0001) with no differences in GCase activity between SCZ and controls (p>0.05). Higher HexSph concentration was linked with higher odds of SCZ status (OR=1.86, p<0.0001). We revealed increase of LysoGb3 concentration in SCZ patients compared to controls (p<0.0001) that was associated with pronounced higher risk of SCZ (OR=41.95, p<0.0001). SCZ patients were characterized by elevated GLA activity compared to controls (p<0.0001) that was associated with higher risk of SCZ (OR=1.47, p=0.0002). GALC activity was increased in SCZ patients compared to controls (p=0.005) and it was associated with earlier age at onset of SCZ by 14.8 years (p=0.033). Lower IDUA activity was found in SCZ patients compared to controls (p=0.032). There was no differences in GAA activity between SCZ patients and controls (p>0.05).
Conclusion: Our results shown the alteration of enzyme activity in SCZ that may support data about the possible link between SCZ and LSDs and suggest the contribution of the role of lysosomal dysfunction in SCZ pathogenesis.
References: 1. Cox T.M. Lysosomal Diseases and Neuropsychiatry: Opportunities to Rebalance the Mind // Front Mol Biosci, 2020. – V.7. – P.177
To cite this abstract in AMA style:
A. Bezrukova, K. Basharova, M. Nikolaev, E. Palchikova, I. Miliukhina, G. Baydakova, N. Zalutskaya, E. Zakharova, S. Pchelina, T. Usenko. Alteration of lysosomal enzymatic activities in blood of patients with schizophrenia [abstract]. Mov Disord. 2022; 37 (suppl 2). https://www.mdsabstracts.org/abstract/alteration-of-lysosomal-enzymatic-activities-in-blood-of-patients-with-schizophrenia/. Accessed November 24, 2024.« Back to 2022 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/alteration-of-lysosomal-enzymatic-activities-in-blood-of-patients-with-schizophrenia/