Disturbed glutathione antioxidative defense is associated with structural brain changes in neuroleptic-naïve first-episode psychosis patients

Glutathione levels and activities of glutathione metabolism enzymes in patients with schizophrenia: A systematic review and meta-analysis

“…Among the 41 GSH studies, 25 studies and one study showed significantly decreased and increased GSH levels, respectively, in patients with SZ (Baxter et al, 2015; Das et al, 2018; Dietrich-Muszalska et al, 2009; Diken et al, 2001; Do et al, 2015; Duval and Tweedie, 2000; Evans et al, 2003; Forman et al, 2009; Fraguas et al, 2017; Hardingham and Do, 2016; Hoftman et al, 2015; Kartalci et al, 2011; Kumar et al, 2018; Langbein et al, 2017; Li et al, 2006; Miljevic et al, 2010a; Mills and Lang, 1996; Nordberg and Arner, 2001; Raffa et al, 2011, 2012a; Simsek et al, 2016; Steullet et al, 2010; Tharoor et al, 2018; Tseng et al, 2008; Wang et al, 2019; Zhang et al, 2010) compared to HCs, while 15 studies did not report any significant difference between the two groups (Barak et al, 1958; Baumann et al, 2016; Brandt et al, 2016; Gysin et al, 2007, 2011; Kartalci et al, 2011; Langbein et al, 2017; Matsuzawa et al, 2008; Parellada et al, 2012; Reid et al, 2019; Rowland et al, 2016a, 2016b; Taylor et al, 2017; Terpstra et al, 2005; Wijtenburg et al, 2017). With regard to GSSG, two and two studies reported decreased and increased levels of GSSG (Ballesteros et al, 2013a; Gawryluk et al, 2011; Raffa et al, 2011, 2012a), respectively, in patients with SZ in comparison with HCs, while five studies noted no difference in the GSSG levels between the two groups (Ivanova et al, 2015; Langbein et al, 201...…”

“…Seven studies included in the present meta-analyses suggest correlations between lower GSH levels and greater severity of clinical symptoms, including cognitive dysfunction (Ballesteros et al, 2013a; Martinez-Cengotitabengoa et al, 2012; Matsuzawa et al, 2008; Nucifora et al, 2017; Raffa et al, 2009, 2011; Wang et al, 2019) while the remaining six studies did not show any associations among them (Altuntas et al, 2000; Dadheech et al, 2012; Gonzalez-Liencres et al, 2014; Martinez-Cengotitabengoa et al, 2014; Mico et al, 2011; Wood et al, 2009). In addition, two studies reported that GSH levels were not associated with brain structure, although these studies demonstrated the relationships between GPx and GR activities and brain structures (Baumann et al, 2016; Langbein et al, 2017). On the other hand, a recent meta-analysis on effectiveness of adjunctive NAC treatment of SZ reported that it might be an effective treatment to improve the symptoms of this disorder with an effect size of 0.74, although it was limited by the small number of randomized controlled trials (Zheng et al, 2018).…”

“…In the present meta-analysis, we found no difference in GR activity between patients with SZ and HCs. However, four out of the seven included studies reported significantly lower GR activity in patients with SZ compared with HCs (Langbein et al, 2017; Miljevic et al, 2010b; Ravikumar et al, 2000; Yao et al, 2006), while one study reported higher GR activity in patients with SZ (Al-Asmari and Khan, 2014). Therefore, hypoactivity of GR in patients with SZ might be confirmed if further research is conducted in a large sample size.…”

Autoimmune phenotypes in schizophrenia reveal novel treatment targets

“…Oxidative stress, as evidenced by a shift in balance in favor of pro- versus antioxidants, results in disrupted redox signaling which is a phenotype increasingly associated with schizophrenia (Do et al, 2015). Biomarkers of oxidative stress such as glutathione, glutathione peroxidase, and superoxide dismutase are thought to reflect this disruption and alterations of these biomarkers have been recorded in schizophrenia and in psychosis (Coughlin et al, 2017; Coughlin et al, 2013; Langbein et al, 2017; Nucifora et al, 2017; Zeni-Graiff et al, 2017; Zhang et al, 2017). N-acetylcysteine, a precursor of glutathione which has potent anti-oxidant as well as anti-inflammatory properties, was found with some variation to significantly improve psychiatric symptom severity and cognition in a variety of psychiatric disorders including schizophrenia (Berk et al, 2008; Chen et al, 2016; Conus et al, 2018; Farokhnia et al, 2013; Minarini et al, 2017; Nitta et al, 2013; Sommer et al, 2014; Zheng et al, 2018).…”

Antioxidant Potential of Psychotropic Drugs: From Clinical Evidence to In Vitro and In Vivo Assessment and toward a New Challenge for in Silico Molecular Design

“…The overview thus far gives a quite good picture of how already existing compounds can have tandem beneficial effects in treating major mental disorders and reducing oxidative stress levels. The employment of machine learning algorithms developed in the last few years to the possible use of antipsychotic or antidepressant drugs as effective antioxidants has also seen a decisive contribution of many researchers [ 118 , 119 , 120 , 121 , 122 , 123 , 124 , 125 ]. However, many of the studies performed so far made use of statistical or classical mechanics-based methodologies (like QSAR, molecular docking and molecular dynamics) [ 126 , 127 , 128 ].…”