The activity of enzymes of glutathione metabolism in blood cells of patients with a high risk of manifestation of endogenous psychoses and patients with the first psychotic episode

Prokhorova T.A.; Tereshkina E.B.; Savushkina O.K.; Boksha I.S.; Vorobeva E.A.; Omel'chenko M.A.; Pomytkin A.N.; Kaleda V.G.; Burbaeva G.Sh.

doi:https://doi.org/10.17116/jnevro201911904147

Prokhorova T.A.

Tereshkina E.B.

Savushkina O.K.

Boksha I.S.

Research Centre of Mental Health

Vorobeva E.A.

Vishnevsky National Medical Research Center for Surgery of the Russia, Moscow, Russia

Omel'chenko M.A.

Pomytkin A.N.

Research Centre of Mental Health

Kaleda V.G.

Nauchnyĭ tsentr psikhicheskogo zdorov'ia RAMN, Moskva

SPIN RSCI: 9035-3290
Scopus AuthorID: 56765570100
ResearcherID: K-5466-2013
ORCID: 0000-0002-1209-1443

Burbaeva G.Sh.

Nauchnyĭ tsentr psikhicheskogo zdorov'ia RAMN, Moskva

The activity of enzymes of glutathione metabolism in blood cells of patients with a high risk of manifestation of endogenous psychoses and patients with the first psychotic episode

Authors:

Prokhorova T.A., Tereshkina E.B., Savushkina O.K., Boksha I.S., Vorobeva E.A., Omel'chenko M.A., Pomytkin A.N., Kaleda V.G., Burbaeva G.Sh.

More about the authors

Journal: S.S. Korsakov Journal of Neurology and Psychiatry. 2019;119(4): 47‑54

DOI: 10.17116/jnevro201911904147

Read: 2588 times

Download PDF (RU)

Contact the author

Table of contents

To cite this article:

Prokhorova TA, Tereshkina EB, Savushkina OK, et al. The activity of enzymes of glutathione metabolism in blood cells of patients with a high risk of manifestation of endogenous psychoses and patients with the first psychotic episode. S.S. Korsakov Journal of Neurology and Psychiatry. 2019;119(4):47‑54. (In Russ.)
https://doi.org/10.17116/jnevro201911904147

Подписка 2026 Журнал неврологии и психиатрии им. С.С. Корсакова (S.S. Korsakov Journal of Neurology and Psychiatry)

Использование инфографики авторами научных работ

Close metadata

Abstract:

Objective. To assess the activity of glutathione reductase (GR) and glutathione-S-transferase (GST) in blood cells of patients at clinical high-risk (HR) state for psychosis, in first-episode patients with schizophrenia and schizoaffective disorder (SD), and control group, and to seek correlations of these biochemical parameters with clinical assessments in patients. Material and methods. The study included male patients at HR (n=21, 16—25 years old), first-episode patients with schizophrenia (F20, n=14, 18—25 years old) and SD (F25, n=20, 16—25 years old), and 12 people of the control group (19—25 years old). Psychometric scales (SOPS, HDRS, and PANSS) and psychopathological methods were employed. GR and GST enzymatic activities were determined spectrophotometrically. Results. The activities of platelet GR and GST in all groups of patients both before and after treatment were lower than in controls (p<0.01). The platelet GST activity was lower in patients at HR compared to patients with schizophrenia before treatment and lower than in patients with SD after treatment (p<0.05), it was higher in patients with schizophrenia than in patients with SD before treatment (p<0.05). Erythrocyte GST activity in patients with HR was lower than in patients with SD after treatment, and in the latter it exceeded that in patients with schizophrenia and controls (p<0.05). Complex and different patterns of changes in the activities of erythrocyte and platelet GR and GST in patients with schizophrenia spectrum disorders, occurring both before the first psychotic episode in the initial stage of disease, and in the first-episode patients, were detected. Conclusion. The activity of glutathione-converting enzymes in endogenous psychoses of the schizophrenic spectrum, including its early stages, can be used as a biomarker for predicting the development of psychosis, the course of disease, and as criteria for evaluation of therapeutic response to antipsychotic treatment.

Keywords:

glutathione reductase

glutathione-S-transferase

platelets

erythrocytes

the first-episode psychosis

high risk for psychosis

Authors:

Prokhorova T.A.

Tereshkina E.B.

Savushkina O.K.

Boksha I.S.

Research Centre of Mental Health

Vorobeva E.A.

Vishnevsky National Medical Research Center for Surgery of the Russia, Moscow, Russia

Omel'chenko M.A.

Pomytkin A.N.

Research Centre of Mental Health

Kaleda V.G.

Nauchnyĭ tsentr psikhicheskogo zdorov'ia RAMN, Moskva

SPIN RSCI: 9035-3290
Scopus AuthorID: 56765570100
ResearcherID: K-5466-2013
ORCID: 0000-0002-1209-1443

Burbaeva G.Sh.

Nauchnyĭ tsentr psikhicheskogo zdorov'ia RAMN, Moskva

Close metadata

References:

McGrath J, Saha S, Chant D, Welham J. The epidemiology of schizophrenia: A concise overview of incidence, prevalence, and mortality. Epidemiologic Reviews. 2008;30(1):67-76. https://doi.org/10.1093/epirev/mxn001
Kirkbride J, Hameed Y, Ankireddypalli G, Ioannidis K, Crane C, Nasir M, Kabacs N, Metastasio A, Jenkins O, Espandian A, Spyridi S, Ralevic D, Siddabattuni S, Walden B, Adeoye A, Perez J, Jones P. The epidemiology of first-episode psychosis in early intervention in psychosis services: Findings from the social epidemiology of psychoses in East Anglia [SEPEA] study. The American Journal of Psychiatry. 2017;174(2):143-153. https://doi.org/10.1176/appi.ajp.2016.16010103
Perälä J, Suvisaari J, Saarni SI, Kuoppasalmi K, Isometsä E, Pirkola S, Partonen T, Tuulio-Henriksson A, Hintikka J, Kieseppä T, Härkänen T, Koskinen S, Lönnqvist J. Lifetime prevalence of psychotic and bipolar I disorders in a general population. Arch Gen Psychiatry. 2007;64(1):19-28. https://doi.org/10.1001/archpsyc.64.1.19
Fusar-Poli P, Borgwardt S, Bechdolf A, Addington J, Riecher-Rossler A. Schultze-Lutter F, Keshavan M, Wood S, Ruhrmann S, Seidman LJ, Valmaggia L, Cannon T, Velthorst E, De Haan L, Cornblatt B, Bonoldi I, Birchwood M, McGlashan T, Carpenter W, McGorry P, Klosterkötter J, McGuire P, Yung A. The psychosis high-risk state. JAMA Psychiatry. 2013;70(1):107-120. https://doi.org/10.1001/jamapsychiatry.2013.269
Fusar-Poli P. The clinical high-risk state for psychosis (CHR-P), Version II. Schizophrenia Bulletin. 2017;43(1):44-47. https://doi.org/10.1093/schbul/sbw158
Cannon TD, Cadenhead K, Cornblatt B, Woods SW, Addington J, Walker E, Seidman LJ, Perkins D, Tsuang M, McGlashan T, Heinssen R. Prediction of psychosis in youth at high clinical risk: a multisite longitudinal study in North America. Arch Gen Psychiatry. 2008;65(1):28-37. https://doi.org/10.1001/archgenpsychiatry.2007.3
Kaleda VG, Omel’chenko MA, Rumyantsev AO. Psikhoticheskij risk v yunosheskom vozraste. Psikhiatriya i Psikhofarmakoterapiya. 2017;19(2):27-33. (In Russ.)
Woodberry K, Shapiro D, Bryant C, Seidman L. Progress and future directions in research on the psychosis prodrome: A review for clinicians. Harvard Review of Psychiatry. 2016;24(2):87-103. https://doi.org/10.1097/HRP.0000000000000109
Wu JQ, Kosten TR, Zhang XY. Free radicals, antioxidant defense systems, and schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry. 2013;46:200-206. https://doi.org/10.1016/j.pnpbp.2013.02.015
Yao JK, Keshavan MS. Antioxidants, redox signaling, and pathophysiology in schizophrenia: an integrative view. Antioxid Redox Signal. 2011;15(7):2011-2035. https://doi.org/10.1089/ars.2010.3603
Barron H, Hafizi S, Andreazza AC, Mizrahi R. Neuroinflammation and Oxidative Stress in Psychosis and Psychosis Risk. Int J Mol Sci. 2017;18(3):e651. https://doi.org/10.3390/ijms18030651
Kim SY, Cohen BM, Chen X, Lukas SE, Shinn AK, Yuksel AC, Li T, Du F, Öngür D. Redox Dysregulation in Schizophrenia Revealed by in vivo NAD+/NADH Measurement. Schizophr Bull. 2017;43(1):197-204. https://doi.org/10.1093/schbul/sbw129
Shchigoreva YuG, Smirnova LP. Vlijanie tipichnyh i atipichnyh nejroleptikov na aktivnosti antioksidantnoj sistemy u bol’nyh shizofreniej. Sibirskij Vestnik Psihiatrii i Narkologii (Prilozhenie «Aktual’nye Voprosy Psihiatrii i Narkologii»). 2011;15:167-169. (In Russ.)
Nebert DW, Vasiliou V. Analysis of the glutathione S-transferase (GST) gene family. Hum Genomics. 2004;1(6):460-464.
Yao JK, Leonard S, Reddy R. Altered glutathione redox state in schizophrenia. Dis Markers. 2006;22(1-2):83-93.
Gysin R, Kraftsik R, Boulat O, Bovet P, Conus P, Comte-Krieger E, Polari A, Steullet P, Preisig M, Teichmann T, Cuénod M, Do KQ. Genetic dysregulation of glutathione synthesis predicts alteration of plasma thiol redox status in schizophrenia. Antioxid Redox Signal. 2011;15:2003-2010. https://doi.org/10.1089/ars.2010.3463
Chang JC, van der Hoeven LH, Haddox CH. Glutathione reductase in the red blood cells. Ann Clin Lab Sci. 1978;8(1):23-29.
Viinamäki H, Marin E, Kuha S. Activities of Glutathione Reductase, S-Transferase, and Peroxidase in Schizophrenic Patients. Nordic Journal of Psychiatry. 1994;48(4):247-250. https://doi.org/10.3109/08039489409078144
Ozornina NV, Ozornin AS, Govorin NV. Possible pathophysiological mechanisms of changes in several cytokines and in the lipid peroxidation and antioxidant defense system in first-episode schizophrenia patients. Neurochemical Journal. 2013;7(3):230-233. (In Russ.) https://doi.org/10.1134/S1819712413030112
Ozornin AS, Ozornina NV, Govorin NV. Izmenenie protsessov lipoperoksidatsii i soderzhaniya zhirnykh kislot v ehritrotsitarnykh membranakh u bol’nykh paranoidnoj shizofreniej. Rossijskij Psikhiatricheskij Zhurnal. 2017;2:47-53. (In Russ.)
Prohorova TA, Savushkina OK, Tereshkina EB, Kaleda VG, Pomytkin AN, Boksha IS, Burbaeva GSh. Aktivnost’ fermentov glutationovogo obmena (glutationreduktazy i glutation-S-transferazy) v trombocitah bol’nyh s jendogennymi psihozami. Zhurnal Nauchnyh Statej «Zdorov’e i Obrazovanie v XXI veke». 2015;17(1):95-97. (In Russ.)
Savushkina OK, Boksha IS, Vorob’eva EA, Burminskij DS, Morozova MA, Burbaeva GSh. Aktivnost’ trombocitarnoj glutationreduktazy u bol’nyh shizofreniej. Vestnik SMUS. 2016;2(13):21-23. (In Russ.)
Langbein HJ, Gussew A, Milleit B, Lavoie S, Amminger GP, Gaser C, Wagner G, Reichenbach JR, Hipler UC, Winter D, Smesny S. Disturbed glutathione antioxidative defense is associated with structural brain changes in neuroleptic-naïve first-episode psychosis patients. Prostaglandins Leukot Essent Fatty Acids. 2017;pii: S0952-3278(16)30221-6. https://doi.org/10.1016/j.plefa.2017.10.005
Da Silva T, Hafizi S, Andreazza AC, Kiang M, Bagby RM, Navas E, Laksono I, Truong P, Gerritsen C, Prce I, Sailasuta N, Mizrahi R. Glutathione, the Major Redox Regulator, in the Prefrontal Cortex of Individuals at Clinical High Risk for Psychosis. Int J Neuropsychopharmacol. 2018;21(4):311-318. https://doi.org/10.1093/ijnp/pyx094
Worthington DJ, Rosemeyer MA. Glutathione Reductase from Human Erythrocytes. Eur J Biochem. 1976;67:231-238. https://doi.org/10.1111/j.1432-1033.1976.tb10654.x
Keen JH, Habig WH, Jakoby WB. Mechanism for the several activities of the glutathione S-transferases. J Biol Chem. 1976;251(20):6183-6188.
Habif S, Mutaf I, Turgan N, Onur E, Duman C, Ozmen D, Bayindir O. Age and gender dependent alterations in the activities of glutathione related enzymes in healthy subjects. Clin Biochem. 2001;34(8):667-671.
Wood SJ, Berger GE, Wellard RM, Proffitt TM, McConchie M, Berk M, McGorry PD, Pantelis C. Medial temporal lobe glutathione concentration in first episode psychosis: a 1H-MRS investigation. Neurobiol Dis. 2009;33(3):354-357. https://doi.org/10.1016/j.nbd.2008.11.018
Xin L, Mekle R, Fournier M, Baumann PS, Ferrari C, Alameda L, Jenni R, Lu H, Schaller B, Cuenod M, Conus P, Gruetter R, Do KQ. Genetic Polymorphism Associated Prefrontal Glutathione and Its Coupling With Brain Glutamate and Peripheral Redox Status in Early Psychosis. Schizophr Bull. 2016;42(5):1185-1196. https://doi.org/10.1093/schbul/sbw038
Jordan W, Dobrowolny H, Bahn S, Bernstein HG, Brigadski T, Frodl T, Isermann B, Lessmann V, Pilz J, Rodenbeck A, Schiltz K,Schwedhelm E, Tumani H, Wiltfang J, Guest PC, Steiner J. Oxidative stress in drug-naïve first episode patients with schizophrenia and major depression: effects of disease acuity and potential confounders. Eur Arch Psychiatry Clin Neurosci. 2018;268(2):129-143. https://doi.org/10.1007/s00406-016-0749-7
Zeni-Graiff M, Rios AC, Maurya PK, Rizzo LB, Sethi S, Yamagata AS, Mansur RB, Pan PM, Asevedo E, Cunha GR, Zugman A, Bressan RA, Gadelha A, Brietzke E. Peripheral levels of superoxide dismutase and glutathione peroxidase in youths in ultra-high riskfor psychosis: a pilot study. CNS Spectr. 2017;17:1-5. https://doi.org/10.1017/S1092852917000803
Sawa A, Seidman LJ. Is Prophylactic Psychiatry around the Corner? Combating Adolescent Oxidative Stress for Adult Psychosis and Schizophrenia Neuron. 2014;83:991-993. https://doi.org/10.1016/j.neuron.2014.08.028
Lavoie S, Berger M, Schlögelhofer M Schäfer MR Rice S Kim S-W, Hesse J, McGorry PD, Smesny S, Amminger GP. Erythrocyte glutathione levels as long-term predictor of transition to psychosis. Transl Psychiatry. 2017;7(3): e1064. https://doi.org/10.1038/tp.2017.30