Increased nitro-oxidative toxicity in association with metabolic syndrome, atherogenicity and insulin resistance in patients with affective disorders

Morelli, Nayara Rampazzo; Maes, Michael; Bonifácio, Kamila Landucci; Vargas, Heber Odebrecht; Nunes, Sandra Odebrecht Vargas; Barbosa, Décio Sabbatini

doi:10.1016/j.jad.2021.07.057

Cited by 32 publications

(48 citation statements)

References 54 publications

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“…In RA, as well as in depression, there are multiple multidirectional interconnections among immune–inflammatory and O&NS pathways leading to a vicious circle between these two pathways. Moreover, such O&NS pathways also play a role in CFS and anxiety disorders [ 43 , 101 ], while similar autoimmune responses are also observed in depression and CFS [ 43 ].…”

Section: Discussionmentioning

confidence: 99%

Pathway Phenotypes Underpinning Depression, Anxiety, and Chronic Fatigue Symptoms Due to Acute Rheumatoid Arthritis: A Precision Nomothetic Psychiatry Analysis

Smesam

Qazmooz

Khayoon

et al. 2022

JPM

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Rheumatoid arthritis (RA) is a chronic inflammatory and autoimmune disorder which affects the joints in the wrists, fingers, and knees. RA is often associated with depressive and anxiety symptoms as well as chronic fatigue syndrome (CFS)-like symptoms. This paper examines the association between depressive symptoms (measured with the Beck Depression Inventory, BDI), anxiety (Hamilton Anxiety Rating Scale, HAMA), CFS-like (Fibro-fatigue Scale) symptoms and immune–inflammatory, autoimmune, and endogenous opioid system (EOS) markers, and lactosylcer-amide (CD17) in RA. The serum biomarkers were assayed in 118 RA and 50 healthy controls. Results were analyzed using the new precision nomothetic psychiatry approach. We found significant correlations between the BDI, FF, and HAMA scores and severity of RA, as assessed with the DAS28-4, clinical and disease activity indices, the number of tender and swollen joints, and patient and evaluator global assessment scores. Partial least squares analysis showed that 69.7% of the variance in this common core underpinning psychopathology and RA symptoms was explained by immune–inflammatory pathways, rheumatoid factor, anti-citrullinated protein antibodies, CD17, and mu-opioid receptor levels. We constructed a new endophenotype class comprising patients with very high immune–inflammatory markers, CD17, RA, affective and CF-like symptoms, and tobacco use disorder. We extracted a reliable and replicable latent vector (pathway phenotype) from immune data, psychopathology, and RA-severity scales. Depression, anxiety, and CFS-like symptoms due to RA are manifestations of the phenome of RA and are mediated by the effects of the same immune–inflammatory, autoimmune, and other pathways that underpin the pathophysiology of RA.

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Section: Discussionmentioning

confidence: 99%

Pathway Phenotypes Underpinning Depression, Anxiety, and Chronic Fatigue Symptoms Due to Acute Rheumatoid Arthritis: A Precision Nomothetic Psychiatry Analysis

Smesam

Qazmooz

Khayoon

et al. 2022

JPM

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“…Mitochondria are considered the primary organ and nicotinamide‐adenine dinucleotide phosphate (NADPH) oxidase is the crucial enzyme responsible for the production of ROS in both cytosol and mitochondria (Figure 2). 86 Several studies have found that patients with MetS have lower levels of various antioxidant enzymes such as glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD) in plasma and higher levels of NADPH oxidase along with several oxidative stress markers, mainly lipid peroxidation products malondialdehyde (MDA), 4‐hydroxynonenal (HNE), and oxidized LDL 90–92 . These highly reactive molecules induce cellular dysfunction of key regulatory enzymes such as pyruvate dehydrogenase complex, proteins (e.g., cytochrome c), and damage vascular endothelial cells, such as that observed in macro‐and microvascular diseases 86,93 .…”

Section: Pathophysiology Of Metsmentioning

confidence: 99%

“…86 Several studies have found that patients with MetS have lower levels of various antioxidant enzymes such as glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD) in plasma and higher levels of NADPH oxidase along with several oxidative stress markers, mainly lipid peroxidation products malondialdehyde (MDA), 4-hydroxynonenal (HNE), and oxidized LDL. [90][91][92] These highly reactive molecules induce cellular dysfunction of key regulatory enzymes such as pyruvate dehydrogenase complex, proteins (e.g., cytochrome c), and damage vascular endothelial cells, such as that observed in macro-and microvascular diseases. 86,93 For example, ROS generated from NADPH oxidase and thioredoxin-interacting protein (TXNIP) stimulate inflammatory pathways mitogen-activated protein kinase (MAPK) and IκB kinase α/β (IKKα/β), and ASK1 and JNK through the transcription upregulation of nuclear factor-κB (NF-κB) and AP1.…”

Section: Oxidative Stress and Metsmentioning

confidence: 99%

Dietary carbohydrates: Pathogenesis and potential therapeutic targets to obesity‐associated metabolic syndrome

Akter

Akhter

Chaudhury³

et al. 2022

BioFactors

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Metabolic syndrome (MetS) is a common feature in obesity, comprising a cluster of abnormalities including abdominal fat accumulation, hyperglycemia, hyperinsulinemia, dyslipidemia, and hypertension, leading to diabetes and cardiovascular diseases (CVD). Intake of carbohydrates (CHO), particularly a sugary diet that rapidly increases blood glucose, triglycerides, and blood pressure levels is the predominant determining factor of MetS. Complex CHO, on the other hand, are a stable source of energy taking a longer time to digest. In particular, resistant starch (RS) or soluble fiber is an excellent source of prebiotics, which alter the gut microbial composition, which in turn improves metabolic control. Altering maternal CHO intake during pregnancy may result in the child developing MetS. Furthermore, lifestyle factors such as physical inactivity in combination with dietary habits may synergistically influence gene expression by modulating genetic and epigenetic regulators transforming childhood obesity into adolescent metabolic disorders. This review summarizes the common pathophysiology of MetS in connection with the nature of CHO, intrauterine nutrition, genetic predisposition, lifestyle factors, and advanced treatment approaches; it also emphasizes how dietary CHO may act as a key element in the pathogenesis and future therapeutic targets of obesity and MetS.

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“…The same shared pathways underpin the comorbidity between mood disorders and MetS [17][18][19][20][21]. Shared biomarkers of mood disorders, T2DM, and MetS comprise increased levels of pro-inflammatory cytokines, malondialdehyde (MDA, indicating lipid peroxidation), nitric oxide (NO) metabolites (indicating increased NO production), and advanced protein oxidation products (AOPPs), and lowered paraoxonase (PON)-1 activity [10,11,22,23]. Nevertheless, the biomarkers of affective symptoms (depression and anxiety) in T2DM are not well established and, consequently, research should focus on the up-or downstream biomarkers of the abovementioned pathways that play a role in depression and anxiety due to T2DM.…”

Section: Introductionmentioning

confidence: 99%

Intersections between Copper, β-Arrestin-1, Calcium, FBXW7, CD17, Insulin Resistance and Atherogenicity Mediate Depression and Anxiety Due to Type 2 Diabetes Mellitus: A Nomothetic Network Approach

Al‐Hakeim

Hadi

Jawad

et al. 2022

JPM

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Type 2 diabetes mellitus (T2DM) is frequently accompanied by affective disorders with a prevalence of comorbid depression of around 25%. Nevertheless, the biomarkers of affective symptoms including depression and anxiety due to T2DM are not well established. The present study delineated the effects of serum levels of copper, zinc, β-arrestin-1, FBXW7, lactosylceramide (LacCer), serotonin, calcium, magnesium on severity of depression and anxiety in 58 men with T2DM and 30 healthy male controls beyond the effects of insulin resistance (IR) and atherogenicity. Severity of affective symptoms was assessed using the Hamilton Depression and Anxiety rating scales. We found that 61.7% of the variance in affective symptoms was explained by the multivariate regression on copper, β-arrestin-1, calcium, and IR coupled with atherogenicity. Copper and LacCer (positive) and calcium and BXW7 (inverse) had significant specific indirect effects on affective symptoms, which were mediated by IR and atherogenicity. Copper, β-arrestin-1, and calcium were associated with affective symptoms above and beyond the effects of IR and atherogenicity. T2DM and affective symptoms share common pathways, namely increased atherogenicity, IR, copper, and β-arrestin-1, and lowered calcium, whereas copper, β-arrestin-1, calcium, LacCer, and FBXW7 may modulate depression and anxiety symptoms by affecting T2DM.

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Increased nitro-oxidative toxicity in association with metabolic syndrome, atherogenicity and insulin resistance in patients with affective disorders

Cited by 32 publications

References 54 publications

Pathway Phenotypes Underpinning Depression, Anxiety, and Chronic Fatigue Symptoms Due to Acute Rheumatoid Arthritis: A Precision Nomothetic Psychiatry Analysis

Pathway Phenotypes Underpinning Depression, Anxiety, and Chronic Fatigue Symptoms Due to Acute Rheumatoid Arthritis: A Precision Nomothetic Psychiatry Analysis

Dietary carbohydrates: Pathogenesis and potential therapeutic targets to obesity‐associated metabolic syndrome

Intersections between Copper, β-Arrestin-1, Calcium, FBXW7, CD17, Insulin Resistance and Atherogenicity Mediate Depression and Anxiety Due to Type 2 Diabetes Mellitus: A Nomothetic Network Approach

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