TY - JOUR
T1 - Glutathione levels and activities of glutathione metabolism enzymes in patients with schizophrenia
T2 - A systematic review and meta-analysis
AU - Tsugawa, Sakiko
AU - Noda, Yoshihiro
AU - Tarumi, Ryosuke
AU - Mimura, Yu
AU - Yoshida, Kazunari
AU - Iwata, Yusuke
AU - Elsalhy, Muhammad
AU - Kuromiya, Minori
AU - Kurose, Shin
AU - Masuda, Fumi
AU - Morita, Shinji
AU - Ogyu, Kamiyu
AU - Plitman, Eric
AU - Wada, Masataka
AU - Miyazaki, Takahiro
AU - Graff-Guerrero, Ariel
AU - Mimura, Masaru
AU - Nakajima, Shinichiro
N1 - Funding Information:
The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the Japan Society for the Promotion of Science and AMED to SN, YN, and MM. The funding agency did not contribute to the study design; the data collection, analyses, and interpretation; the writing of the manuscript; and the decision to submit the manuscript for publication.
Publisher Copyright:
© The Author(s) 2019.
PY - 2019/10/1
Y1 - 2019/10/1
N2 - Background: Glutathione is among the important antioxidants to prevent oxidative stress. However, the relationships between abnormality in the glutathione system and pathophysiology of schizophrenia remain uncertain due to inconsistent findings on glutathione levels and/or glutathione-related enzyme activities in patients with schizophrenia. Methods: A systematic literature search was conducted using Embase, Medline, PsycINFO, and PubMed. Original studies, in which three metabolite levels (glutathione, glutathione disulfide, and total glutathione (glutathione+glutathione disulfide)) and five enzyme activities (glutathione peroxidase, glutathione reductase, glutamate-cysteine ligase, glutathione synthetase, and glutathione S-transferase) were measured with any techniques in both patients with schizophrenia and healthy controls, were included. Standardized mean differences were calculated to determine the group differences in the glutathione levels with a random-effects model. Results: We identified 41, 9, 15, 38, and seven studies which examined glutathione, glutathione disulfide, total glutathione, glutathione peroxidase, and glutathione reductase, respectively. Patients with schizophrenia had lower levels of both glutathione and total glutathione and decreased activity of glutathione peroxidase compared to controls. Glutathione levels were lower in unmedicated patients with schizophrenia than those in controls while glutathione levels did not differ between patients with first-episode psychosis and controls. Conclusions: Our findings suggested that there may be glutathione deficits and abnormalities in the glutathione redox cycle in patients with schizophrenia. However, given the small number of studies examined the entire glutathione system, further studies are needed to elucidate a better understanding of disrupted glutathione function in schizophrenia, which may pave the way for the development of novel therapeutic strategies in this disorder.
AB - Background: Glutathione is among the important antioxidants to prevent oxidative stress. However, the relationships between abnormality in the glutathione system and pathophysiology of schizophrenia remain uncertain due to inconsistent findings on glutathione levels and/or glutathione-related enzyme activities in patients with schizophrenia. Methods: A systematic literature search was conducted using Embase, Medline, PsycINFO, and PubMed. Original studies, in which three metabolite levels (glutathione, glutathione disulfide, and total glutathione (glutathione+glutathione disulfide)) and five enzyme activities (glutathione peroxidase, glutathione reductase, glutamate-cysteine ligase, glutathione synthetase, and glutathione S-transferase) were measured with any techniques in both patients with schizophrenia and healthy controls, were included. Standardized mean differences were calculated to determine the group differences in the glutathione levels with a random-effects model. Results: We identified 41, 9, 15, 38, and seven studies which examined glutathione, glutathione disulfide, total glutathione, glutathione peroxidase, and glutathione reductase, respectively. Patients with schizophrenia had lower levels of both glutathione and total glutathione and decreased activity of glutathione peroxidase compared to controls. Glutathione levels were lower in unmedicated patients with schizophrenia than those in controls while glutathione levels did not differ between patients with first-episode psychosis and controls. Conclusions: Our findings suggested that there may be glutathione deficits and abnormalities in the glutathione redox cycle in patients with schizophrenia. However, given the small number of studies examined the entire glutathione system, further studies are needed to elucidate a better understanding of disrupted glutathione function in schizophrenia, which may pave the way for the development of novel therapeutic strategies in this disorder.
KW - Schizophrenia
KW - glutathione
KW - oxidative stress
KW - redox dysregulation
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U2 - 10.1177/0269881119845820
DO - 10.1177/0269881119845820
M3 - Review article
C2 - 31039654
AN - SCOPUS:85065421008
SN - 0269-8811
VL - 33
SP - 1199
EP - 1214
JO - Journal of Psychopharmacology
JF - Journal of Psychopharmacology
IS - 10
ER -
