Antioxidant Enzymes and Weight Gain in Drug-naive First-episode Schizophrenia Patients Treated with Risperidone for 12 Weeks: A Prospective Longitudinal Study

Overview

Journal Curr Neuropharmacol

Publisher Bentham Science Publishers

Date 2021 Sep 21

PMID 34544343

Citations 10

Authors

Haixia Liu

Rui Yu

Yanan Gao

Xirong Li

Xiaoni Guan

Kosten Thomas

Meihong Xiu

Xiangyang Zhang

Affiliations

Soon will be listed here.

Abstract

Background: Oxidative stress plays an important role in weight gain induced by antipsychotics in schizophrenia (SCZ). However, little is known about how antioxidant enzymes are involved in weight gain caused by risperidone monotherapy in antipsychotics-naïve first-episode (ANFE) patients with SCZ. Therefore, the main purpose of this study was to investigate the effects of risperidone on several antioxidant enzymes in patients with ANFE SCZ and the relationship between weight gain and changes in antioxidant enzyme activities.

Objective: The activities of plasma superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), as well as the levels of malondialdehyde (MDA) were measured in 225 ANFE patients and 125 healthy controls.

Methods: Patients were treated with risperidone monotherapy for 12 weeks. Clinical symptoms, antioxidant enzyme activities, and MDA levels were measured at baseline and during follow-up.

Results: Compared with healthy controls, the patients showed higher activities of SOD and CAT but lower MDA levels and GPx activity. At baseline, the CAT activity was associated with body weight or BMI. Further, based on a 7% weight increase from baseline to follow-up, we found 75 patients in the weight gain (WG) group and 150 patients in the non-WG group. Comparing SOD, CAT, GPx activities and MDA levels between the WG group and the non-WG group at baseline and during the 12-week follow-up, it was found that after treatment, the SOD activity in the WG group increased while the MDA level decreased in the non-WG group. Moreover, baseline SOD and GPx activities were predictors of weight gain at 12-week follow-up.

Conclusion: These results suggest that the antioxidant defense system may have predictive value for the weight gain of ANFE SCZ patients after risperidone treatment.

Citing Articles

Variations to plasma HO levels and TAC in chronical medicated and treatment-resistant male schizophrenia patients: Correlations with psychopathology.

Yang H, Sun W, Yang M, Li J, Zhang J, Zhang X Schizophrenia (Heidelb). 2024; 10(1):45.

PMID: 38605069 PMC: 11009317. DOI: 10.1038/s41537-024-00468-y.

Glucose Metabolism and Sex Hormones in Male Patients with Medication-naïve First-episode Schizophrenia: A Large-scale Cross-sectional Study.

Xiu M, Hao M, Liu C, Sun M, Lang X Curr Neuropharmacol. 2024; 22(13):2263-2270.

PMID: 38549523 PMC: 11337684. DOI: 10.2174/1570159X22666240212141602.

Smoking, Symptoms Improvement, and Total Antioxidant Capacity in Patients with Drug-naive First-episode Schizophrenia: A Prospective Cohort Study.

Gao Z, Xiu M, Liu J, Wu F, Zhang X Curr Neuropharmacol. 2023; 22(10):1733-1741.

PMID: 37859307 PMC: 11284715. DOI: 10.2174/1570159X22666231019105328.

Predicting antipsychotic-induced weight gain in first episode psychosis - A field-wide systematic review and meta-analysis of non-genetic prognostic factors.

Fitzgerald I, Sahm L, Byrne A, OConnell J, Ensor J, Ni Dhubhlaing C Eur Psychiatry. 2023; 66(1):e42.

PMID: 37278237 PMC: 10305761. DOI: 10.1192/j.eurpsy.2023.2417.

Smoking Affects the Predictive Roles of Antioxidant Enzymes in the Clinical Response to Risperidone in Schizophrenia: A Large-scale Cohort Study.

Xiu M, Song X, Yang H, Huang X, Wu F, Zhang X Curr Neuropharmacol. 2023; 21(10):2151-2158.

PMID: 37132112 PMC: 10556368. DOI: 10.2174/1570159X21666230502125800.

References

Aringhieri S, Kolachalam S, Gerace C, Carli M, Verdesca V, Brunacci M . Clozapine as the most efficacious antipsychotic for activating ERK 1/2 kinases: Role of 5-HT receptor agonism. Eur Neuropsychopharmacol. 2017; 27(4):383-398. DOI: 10.1016/j.euroneuro.2017.02.005. View

Padurariu M, Ciobica A, Dobrin I, Stefanescu C . Evaluation of antioxidant enzymes activities and lipid peroxidation in schizophrenic patients treated with typical and atypical antipsychotics. Neurosci Lett. 2010; 479(3):317-20. DOI: 10.1016/j.neulet.2010.05.088. View

Correll C, Kane J, Manu P . Obesity and coronary risk in patients treated with second-generation antipsychotics. Eur Arch Psychiatry Clin Neurosci. 2010; 261(6):417-23. PMC: 3125452. DOI: 10.1007/s00406-010-0177-z. View

Kay S, Fiszbein A, Opler L . The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull. 1987; 13(2):261-76. DOI: 10.1093/schbul/13.2.261. View

Lohr J . Oxygen radicals and neuropsychiatric illness. Some speculations. Arch Gen Psychiatry. 1991; 48(12):1097-106. DOI: 10.1001/archpsyc.1991.01810360061009. View

Liao J, Zhang Y, Chen X, Zhang J . The Roles of Peroxiredoxin 6 in Brain Diseases. Mol Neurobiol. 2021; 58(9):4348-4364. DOI: 10.1007/s12035-021-02427-5. View

Hendouei N, Farnia S, Mohseni F, Salehi A, Bagheri M, Shadfar F . Alterations in oxidative stress markers and its correlation with clinical findings in schizophrenic patients consuming perphenazine, clozapine and risperidone. Biomed Pharmacother. 2018; 103:965-972. DOI: 10.1016/j.biopha.2018.04.109. View

Maayan L, Correll C . Management of antipsychotic-related weight gain. Expert Rev Neurother. 2010; 10(7):1175-200. PMC: 3501406. DOI: 10.1586/ern.10.85. View

Flatow J, Buckley P, Miller B . Meta-analysis of oxidative stress in schizophrenia. Biol Psychiatry. 2013; 74(6):400-9. PMC: 4018767. DOI: 10.1016/j.biopsych.2013.03.018. View

10.

Furukawa S, Fujita T, Shimabukuro M, Iwaki M, Yamada Y, Nakajima Y . Increased oxidative stress in obesity and its impact on metabolic syndrome. J Clin Invest. 2004; 114(12):1752-61. PMC: 535065. DOI: 10.1172/JCI21625. View

11.

Gentile S . Contributing factors to weight gain during long-term treatment with second-generation antipsychotics. A systematic appraisal and clinical implications. Obes Rev. 2009; 10(5):527-42. DOI: 10.1111/j.1467-789X.2009.00589.x. View

12.

Lopez-Domenech S, Banuls C, Diaz-Morales N, Escribano-Lopez I, Morillas C, Veses S . Obesity impairs leukocyte-endothelium cell interactions and oxidative stress in humans. Eur J Clin Invest. 2018; 48(8):e12985. DOI: 10.1111/eci.12985. View

13.

Lieberman J, Stroup T, McEvoy J, Swartz M, Rosenheck R, Perkins D . Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med. 2005; 353(12):1209-23. DOI: 10.1056/NEJMoa051688. View

14.

Monte A, Mello B, Borella V, Araujo T, da Silva F, de Sousa F . Two-hit model of schizophrenia induced by neonatal immune activation and peripubertal stress in rats: Study of sex differences and brain oxidative alterations. Behav Brain Res. 2017; 331:30-37. DOI: 10.1016/j.bbr.2017.04.057. View

15.

Wu J, Kosten T, Zhang X . Free radicals, antioxidant defense systems, and schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry. 2013; 46:200-6. DOI: 10.1016/j.pnpbp.2013.02.015. View

16.

An H, Du X, Huang X, Qi L, Jia Q, Yin G . Obesity, altered oxidative stress, and clinical correlates in chronic schizophrenia patients. Transl Psychiatry. 2018; 8(1):258. PMC: 6265271. DOI: 10.1038/s41398-018-0303-7. View

17.

SCHOTTE A, Janssen P, Gommeren W, Luyten W, Van Gompel P, Lesage A . Risperidone compared with new and reference antipsychotic drugs: in vitro and in vivo receptor binding. Psychopharmacology (Berl). 1996; 124(1-2):57-73. DOI: 10.1007/BF02245606. View

18.

De Hert M, Detraux J, van Winkel R, Yu W, Correll C . Metabolic and cardiovascular adverse effects associated with antipsychotic drugs. Nat Rev Endocrinol. 2011; 8(2):114-26. DOI: 10.1038/nrendo.2011.156. View

19.

Gunes M, Camkurt M, Bulut M, Demir S, Okan Ibiloglu A, Cemal Kaya M . Evaluation of Paraoxonase, Arylesterase and Malondialdehyde Levels in Schizophrenia Patients Taking Typical, Atypical and Combined Antipsychotic Treatment. Clin Psychopharmacol Neurosci. 2016; 14(4):345-350. PMC: 5083945. DOI: 10.9758/cpn.2016.14.4.345. View

20.

Perry J, Shin D, Getzoff E, Tainer J . The structural biochemistry of the superoxide dismutases. Biochim Biophys Acta. 2009; 1804(2):245-62. PMC: 3098211. DOI: 10.1016/j.bbapap.2009.11.004. View