Are there differences in lipid peroxidation and immune biomarkers between major depression and bipolar disorder: Effects of melancholia, atypical depression, severity of illness, episode number, suicidal ideation and prior suicide attempts

Sowa-Kućma, Magdalena; Styczeń, Krzysztof; Siwek, Marcin; Misztak, Paulina; Nowak, Rafał; Dudek, Dominika; Rybakowski, Janusz; Nowak, Gabriel; Maes, Michaël

doi:10.1016/j.pnpbp.2017.08.024

Cited by 96 publications

(71 citation statements)

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“…Recently, we also detected significant differences in immune profiles between MDD and BD with increased levels of interleukin (IL)-1β, IL-10, IL-12, tumor necrosis factor (TNF)-α, and soluble TNF receptor (TNFR)-1 in MDD versus BD and increased IL-6, IL-18, IL-33, sTNFR-2, ST2 (ILR Like 1) and KLOTHO in BD as compared with MDD (Brunoni et al, submitted). On the other hand, no significant differences in immune profiles (including IL-6, sIL-6R, sIL-2R, acute-phase proteins) or oxidative stress (aldehyde formation) could be found between MDD and BD (Maes, 1995;Maes et al, 1997;Sowa-Kućma et al, 2018a). All in all, the current study as well previous studies indicate that the immune pathophysiology of MDD and BD and BP1 and BP2 may be different.…”

Section: Discussionsupporting

confidence: 53%

“…To the best of our knowledge, this is the first study showing increased bacterial translocation in MDD/BD patients with melancholia. Previously, there were some reports that melancholia is accompanied by more pronounced aberrations in immune and oxidative stress pathways as compared with non-melancholic depression including increased levels of sIL-6R, aldehyde formation, and TNF-α signaling (Siwek et al, 2017;Sowa-Kućma et al, 2018b, 2018a.…”

Section: Discussionmentioning

confidence: 99%

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Increased Serum Immunoglobulin Responses to Gut Commensal Gram-Negative Bacteria in Unipolar Major Depression and Bipolar Disorder Type 1, Especially When Melancholia is Present

Simeonova

Stoyanov

Leunis³

et al. 2019

Preprint

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Major depression (MDD) is accompanied by higher serum IgM/IgA responses to LPS of Gram-negative bacteria, suggesting increased bacterial translocation and gut dysbiosis. Gut dysbiosis may occur in bipolar disorder (BD) and there are differences between MDD and BD type 1 (BP1) and -2 (BP2) in nitro-oxidative stress biomarkers associated with leaky gut. This study examines serum IgM/IgA responses directed to LPS of 6 Gram-negative bacteria in 29 BP1, 37 BP2, 44 MDD and 30 healthy individuals. MDD plus BD was best discriminated from controls by increased IgM/IgA responses to Pseudomonas aeruginosa. BP1 patients showed higher IgM responses to Morganella morganii as compared with MDD and BP2 patients. Patients with melancholia showed higher IgA responses to Citrobacter koseri as compared to controls and non-melancholic depression. The total score on the Hamilton Depression Rating Scale was significantly associated with IgA responses, especially C. koseri. IgG responses to oxidized low-density lipoprotein were significantly associated with signs of increased bacterial translocation. In conclusion, not only MDD but also BP1 and BP2 are accompanied by an immune response due to the increased load of plasma LPS of gut commensal bacteria while these aberrations in the gut-brain axis are most pronounced in BP1 and patients with melancholic features. Activated oxidative stress pathways and autoimmune responses to oxidative specific epitopes in mood disorders may be driven by a breakdown in gut paracellular, transcellular and/or vascular pathways. If replicated, drugs that protect the integrity of the gut barrier may offer novel therapeutic opportunities for BP1 and MDD.

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Section: Discussionsupporting

confidence: 53%

Section: Discussionmentioning

confidence: 99%

Increased Serum Immunoglobulin Responses to Gut Commensal Gram-Negative Bacteria in Unipolar Major Depression and Bipolar Disorder Type 1, Especially When Melancholia is Present

Simeonova

Stoyanov

Leunis³

et al. 2019

Preprint

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“…Other studies were unable to find differences in aldehyde formation between BP1 and BP2 patients in an acute depressive state. 7 It is possible that these differences between studies may be explained by nitrosylation being a trait biomarker and aldehyde formation being a state and trait biomarker. Thus, aldehyde formation is significantly associated with severity of illness and staging of illness as indicated by recurrent depressive and manic episodes and suicidal behaviors, 7 while increased nitrosylation is not associated with severity of illness and staging (this study) but is associated with a lifetime history of depression.…”

Section: Discussionmentioning

confidence: 99%

“…6 There are not many studies that directly compare oxidative biomarkers among patients with BP1 and BP2 in an acute depressive state. For example, Sowa-Kucma et al 7 reported that there are no significant differences in aldehyde formation (TBARS levels) between subjects with MDD and BP disorder (BP1 and BP2) in an acute phase of illness.…”

Section: Introductionmentioning

confidence: 99%

Upregulation of the Nitrosylome in Bipolar Disorder Type 1 (BP1), but not BP2, and Major Depression: Increased IgM Antibodies to Nitrosylated Conjugates are Associated with Indicants of Leaky Gut

Maes¹,

Simeonova²,

Stoyanov³

et al. 2019

Preprint

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Objective: Major depression (MDD) and a lifetime history of MDD are characterized by increased nitrosylation, while bipolar disorder type 1 (BP1), but not BP2, is accompanied by highly increased levels of oxidative stress and nitric oxide (NO) production. Nevertheless, it is unknown whether nitrosylation is involved in BP and whether there are differences in nitrosylation between BP1 and BP2.Methods: Serum IgM antibodies directed against nitroso (NO)-adducts were examined in MDD, BP1, BP2 and healthy controls, namely IgM responses to NO-cysteine, NO-tryptophan (NOW), NO-arginine and NO-albumin (SBA) in association with IgA/IgM responses to Gram-negative bacteria, IgG responses to oxidized low-density lipoprotein (oxLDL) and serum peroxides.Results: Serum IgM levels against NO adducts were significantly higher in BP1 and MDD as compared with healthy controls, whereas BP2 patients occupied an intermediate position. IgM responses to NO-albumin were significantly higher in BP1 and MDD than in BP2 patients. There were highly significant associations between the IgM responses to NO-adducts and IgG responses to oxLDL and IgA/IgM responses to Gram-negative bacteria.Conclusions: BP1 and MDD are characterized by an upregulation of the nitrosylome (the proteome of nitrosylated proteins), and increased IgM responses to nitrosylated conjugates. Increased nitrosylation may be driven by increased bacterial translocation and is associated with lipid peroxidation processes. Innate like (B1 and marginal zone) B cells and increased nitrosylation may play a key role in the major affective disorders through activation of immune-inflammatory and oxidative pathways, cardiovascular comorbidity and impairments in antioxidant defenses, neuro-glial interactions, synaptic plasticity, neuroprotection, neurogenesis, etc.

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“…Although many studies indicate increased lipid peroxidation in MDD, the first study was recently published that evaluated this parameter in TRD patients. Sowa-Kucma et al found that TRD was accompanied by high levels of lipid per-oxidation compared with non-TRD patients [189]. Another previous study investigated baseline OS markers (e.g., vitamin C and GPx) as predictors of antidepressant treatment response, finding negative results [190].…”

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confidence: 99%

Targeting Inflammatory-Mitochondrial Response in Major Depression: Current Evidence and Further Challenges

Visentin

Colombo

Scotton

et al. 2020

Oxidative Medicine and Cellular Longevity

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The prevalence of psychiatric disorders has increased in recent years. Among existing mental disorders, major depressive disorder (MDD) has emerged as one of the leading causes of disability worldwide, affecting individuals throughout their lives. Currently, MDD affects 15% of adults in the Americas. Over the past 50 years, pharmacotherapy, psychotherapy, and brain stimulation have been used to treat MDD. The most common approach is still pharmacotherapy; however, studies show that about 40% of patients are refractory to existing treatments. Although the monoamine hypothesis has been widely accepted as a molecular mechanism to explain the etiology of depression, its relationship with other biochemical phenomena remains only partially understood. This is the case of the link between MDD and inflammation, mitochondrial dysfunction, and oxidative stress. Studies have found that depressive patients usually exhibit altered inflammatory markers, mitochondrial membrane depolarization, oxidized mitochondrial DNA, and thus high levels of both central and peripheral reactive oxygen species (ROS). The effect of antidepressants on these events remains unclear. Nevertheless, the effects of ROS on the brain are well known, including lipid peroxidation of neuronal membranes, accumulation of peroxidation products in neurons, protein and DNA damage, reduced antioxidant defenses, apoptosis induction, and neuroinflammation. Antioxidants such as ascorbic acid, tocopherols, and coenzyme Q have shown promise in some depressive patients, but without consensus on their efficacy. Hence, this paper provides a review of MDD and its association with inflammation, mitochondrial dysfunction, and oxidative stress and is aimed at thoroughly discussing the putative links between these events, which may contribute to the design and development of new therapeutic approaches for patients.

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Are there differences in lipid peroxidation and immune biomarkers between major depression and bipolar disorder: Effects of melancholia, atypical depression, severity of illness, episode number, suicidal ideation and prior suicide attempts

Cited by 96 publications

References 98 publications

Increased Serum Immunoglobulin Responses to Gut Commensal Gram-Negative Bacteria in Unipolar Major Depression and Bipolar Disorder Type 1, Especially When Melancholia is Present

Increased Serum Immunoglobulin Responses to Gut Commensal Gram-Negative Bacteria in Unipolar Major Depression and Bipolar Disorder Type 1, Especially When Melancholia is Present

Upregulation of the Nitrosylome in Bipolar Disorder Type 1 (BP1), but not BP2, and Major Depression: Increased IgM Antibodies to Nitrosylated Conjugates are Associated with Indicants of Leaky Gut

Targeting Inflammatory-Mitochondrial Response in Major Depression: Current Evidence and Further Challenges

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