Plasma glutathione suggests oxidative stress is equally present in early‐ and late‐onset bipolar disorder

Singh, Nisha; McMahon, Hannah; Bilderbeck, Amy C.; Reed, Zoe E; Tunbridge, Elizabeth M.; Brett, Daniel; Geddes, John; Churchill, Grant C.; Goodwin, Guy M.

doi:10.1111/bdi.12640

Cited by 10 publications

(4 citation statements)

References 26 publications

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“…94 Both antioxidants GSH and uric acid could be considered trait markers of BD, as they appear to be decreased and increased, respectively, in euthymia. Moreover, it seems that GSH is not affected by the age at BD onset, as reported by an English study comparing 26 early‐onset with 20 late‐onset BD patients that did not find significant group differences in GSH 43 …”

Section: Discussionmentioning

confidence: 69%

“…Strengths of this study include some relevant differences compared to previous meta‐analyses of oxidative stress markers and antioxidants in BD patients compared with HCs 43,44 . To control for patient heterogeneity, we performed stratified analyses according to the affective phase/polarity of BD whenever possible, ie, mania, bipolar depression and euthymia.…”

Section: Discussionmentioning

confidence: 99%

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Oxidative stress parameters and antioxidants in patients with bipolar disorder: Results from a meta‐analysis comparing patients, including stratification by polarity and euthymic status, with healthy controls

et al. 2020

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Objective To investigate oxidative stress markers and antioxidants in bipolar disorder (BD). Methods Electronic MEDLINE/PubMed/Cochrane‐Library/Scopus/TripDatabase search until 06/30/2019 for studies comparing antioxidant or oxidative stress markers between BD and healthy controls (HCs). Standardized mean differences (SMD) and 95% confidence intervals (CIs) were calculated for ≥3 studies. Results Forty‐four studies (n = 3,767: BD = 1,979; HCs = 1,788) reported on oxidative stress markers malondialdehyde (MDA), thiobarbituric acid reactive substances (TBARS), and total nitrites; antioxidants glutathione (GSH), uric acid, and zinc; or antioxidantenhancing enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), and GSH‐transferase (GST). Compared with HCs, BD was associated with higher GST (P = .01), CAT (P = .02), nitrites (P < .0001), TBARS (P < .0001), MDA (P = .01), uric acid (P < .0001), and lower GSH (P = .006), without differences in SOD, GPX, and zinc. Compared to HCs, levels were higher in BD‐mania for TBARS (P < .0001) and uric acid (P < .0001); in BD‐depression for TBARS (P = .02); and BD‐euthymia for uric acid (P = .03). Uric acid levels were higher in BD‐mania vs BD‐depression (P = .002), but not vs BD euthymia. TBARS did not differ between BD‐mania and BD‐depression. Medication‐free BD‐mania patients had higher SOD (P = .02) and lower GPX (P < .0001) than HCs. After treatment, BD did not differ from HCs regarding SOD and GPX. Conclusions Beyond a single biomarker of oxidative stress, the combination of several parameters appears to be more informative for BD in general and taking into account illness polarity. BD is associated with an imbalance in oxidative stress with some phase‐specificity for uric acid and TBARS and possible treatment benefits for SOD and GPX. Future studies should take into account confounding factors that can modify oxidative stress status and simultaneously measure oxidative stress markers and antioxidants including different blood sources.

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Section: Discussionmentioning

confidence: 69%

Section: Discussionmentioning

confidence: 99%

Oxidative stress parameters and antioxidants in patients with bipolar disorder: Results from a meta‐analysis comparing patients, including stratification by polarity and euthymic status, with healthy controls

et al. 2020

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“…This outcome disrupts calcium homeostasis, leading to elevated calcium [74]. SOD and glutathione are key components of the antioxidant defense against OS [72,123]. Therefore, increased SOD activity may be seen as a mechanism of mitigating increased oxidative damage in BD [81].…”

Section: Oxidative Damage In Bdmentioning

confidence: 99%

Therapeutic Interventions to Mitigate Mitochondrial Dysfunction and Oxidative Stress–Induced Damage in Patients with Bipolar Disorder

Madireddy

2022

IJMS

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Bipolar disorder (BD) is characterized by mood changes, including recurrent manic, hypomanic, and depressive episodes, which may involve mixed symptoms. Despite the progress in neurobiological research, the pathophysiology of BD has not been extensively described to date. Progress in the understanding of the neurobiology driving BD could help facilitate the discovery of therapeutic targets and biomarkers for its early detection. Oxidative stress (OS), which damages biomolecules and causes mitochondrial and dopamine system dysfunctions, is a persistent finding in patients with BD. Inflammation and immune dysfunction might also play a role in BD pathophysiology. Specific nutrient supplements (nutraceuticals) may target neurobiological pathways suggested to be perturbed in BD, such as inflammation, mitochondrial dysfunction, and OS. Consequently, nutraceuticals may be used in the adjunctive treatment of BD. This paper summarizes the possible roles of OS, mitochondrial dysfunction, and immune system dysregulation in the onset of BD. It then discusses OS-mitigating strategies that may serve as therapeutic interventions for BD. It also analyzes the relationship between diet and BD as well as the use of nutritional interventions in the treatment of BD. In addition, it addresses the use of lithium therapy; novel antipsychotic agents, including clozapine, olanzapine, risperidone, cariprazine, and quetiapine; and anti-inflammatory agents to treat BD. Furthermore, it reviews the efficacy of the most used therapies for BD, such as cognitive–behavioral therapy, bright light therapy, imagery-focused cognitive therapy, and electroconvulsive therapy. A better understanding of the roles of OS, mitochondrial dysfunction, and inflammation in the pathogenesis of bipolar disorder, along with a stronger elucidation of the therapeutic functions of antioxidants, antipsychotics, anti-inflammatory agents, lithium therapy, and light therapies, may lead to improved strategies for the treatment and prevention of bipolar disorder.

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“…As a methodological strength, we enhanced our approach by calculating a composite copy number through the arithmetic mean of three genes (i.e., ND1, ND4, and CYTB). This approach was based on the literature, where most studies utilized the ND1 gene as the sole mitochondrial gene (37,39,54,62,72), while other studies employed CYTB, ND4, or ND5 genes (61,73). This sets us apart from the majority of previous studies that determined mtDNA copy numbers using only one (32,38,54,59,72,(74)(75)(76) or two mitochondrial genes (13,49,77,78).…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial DNA oxidation, methylation, and copy number alterations in major and bipolar depression

Ceylan,

Karacicek,

Tufekci

et al. 2023

Front. Psychiatry

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BackgroundMood disorders are common disabling psychiatric disorders caused by both genetic and environmental factors. Mitochondrial DNA (mtDNA) modifications and epigenetics are promising areas of research in depression since mitochondrial dysfunction has been associated with depression. In this study we aimed to investigate the mtDNA changes in depressive disorder (MDD) and bipolar disorder (BD).MethodsDisplacement loop methylation (D-loop-met), relative mtDNA copy number (mtDNA-cn) and mtDNA oxidation (mtDNA-oxi) were investigated in DNA samples of individuals with MDD (n = 34), BD (n = 23), and healthy controls (HC; n = 40) using the Real-Time Polymerase Chain Reaction (RT-PCR). Blood samples were obtained from a subset of individuals with MDD (n = 15) during a depressive episode (baseline) and after remission (8th week).ResultsThe study groups exhibited significant differences in D-loop-met (p = 0.020), while relative mtDNA-cn and mtDNA-oxi showed comparable results. During the remission phase (8th week), there were lower levels of relative mtDNA-cn (Z = −2.783, p = 0.005) and D-loop-met (Z = −3.180, p = 0.001) compared to the acute MDD baseline, with no significant change in mtDNA-oxi levels (Z = −1.193, p = 0.233).ConclusionOur findings indicate significantly increased D-loop methylation in MDD compared to BD and HCs, suggesting distinct mtDNA modifications in these conditions. Moreover, the observed alterations in relative mtDNA-cn and D-loop-met during remission suggest a potential role of mtDNA alterations in the pathophysiology of MDD. Future studies may provide valuable insights into the dynamics of mtDNA modifications in both disorders and their response to treatment.

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Plasma glutathione suggests oxidative stress is equally present in early‐ and late‐onset bipolar disorder

Cited by 10 publications

References 26 publications

Oxidative stress parameters and antioxidants in patients with bipolar disorder: Results from a meta‐analysis comparing patients, including stratification by polarity and euthymic status, with healthy controls

Oxidative stress parameters and antioxidants in patients with bipolar disorder: Results from a meta‐analysis comparing patients, including stratification by polarity and euthymic status, with healthy controls

Therapeutic Interventions to Mitigate Mitochondrial Dysfunction and Oxidative Stress–Induced Damage in Patients with Bipolar Disorder

Mitochondrial DNA oxidation, methylation, and copy number alterations in major and bipolar depression

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