ARTICLE | doi:10.20944/preprints202012.0457.v1
Subject: Medicine & Pharmacology, Allergology Keywords: deficit schizophrenia; neuro-immune; inflammation; oxidative and nitrosative stress; antioxidants; biomarkers; IgM; autoimmune
Online: 18 December 2020 (11:50:42 CET)
Recently, a breakdown of paracellular and vascular pathways and activated neuroimmune and oxidative pathways were established in (deficit) schizophrenia. The aim of the current study was to delineate a) the differences in these pathways between stable phase, first (FES) and multiple (MES) episode schizophrenia, and b) the pathways that determine the behavioral-cognitive-physical-psychosocial (BCPS)-worsening in FES/MES. This study included 21 FES and 58 FES patients and 40 healthy controls and measured indicants of serum IgA to C1q, and leaky gut, immune activation, and oxidative stress toxicity (OSTOX) biomarkers. We constructed a BCPS-worsening index by extracting a latent vector from symptomatic, neurocognitive, and quality of life data. FES patients showed significantly higher IgA to C1q, cadherin, catenin, plasmalemma vesicle-associated protein, and IgA/IgM to Gram-negative bacteria than FES patients and controls. In FES patients, the BCPS-worsening score was predicted (48.7%) by IgA to Klebsiella pneumoniae and lowered paraoxonase 1 activity. In MES patients, the BCPS-worsening score was explained (42.7%) by increased tumor necrosis factor-α, OSTOX, and number of episodes. In schizophrenia, 34.0% of the variance in the BCPS-worsening score was explained by IgA to K. pneumoniae, OSTOX, and number of episodes. Increased IgA to K. pneumoniae was the single best predictor of residual psychotic symptoms in FES and MES. This study delineated different mechanistic processes in FES, including breakdown of adherens junctions, bacterial translocation, and C1q circulating immune complexes; and FES, including immune and oxidative stress neurotoxic pathways. FES and MES comprise different staging subtypes, i.e., FES and MES with and without worsening.
ARTICLE | doi:10.20944/preprints202103.0487.v1
Subject: Medicine & Pharmacology, Allergology Keywords: Major depression; Bipolar disorder; Metabolic syndrome; oxidative and nitrosative stress, antioxidants; biomarkers.
Online: 18 March 2021 (15:56:56 CET)
Background: There is a strong comorbidity between mood disorders and metabolic syndrome (MetS). Increased levels of reactive oxygen and nitrogen species (RONS) and nitro-oxidative stress toxicity (NOSTOX) partially underpin this comorbidity.Aims: To examine the associations of RONS/NOSTOX biomarkers with MetS after adjusting for the significant effects of mood disorders (major depression, and bipolar type 1 and 2), generalized anxiety disorder (GAD), tobacco use disorder (TUD), and male sex.Methods: The study included subjects with (n=65) and without (n=107) MetS and measured levels of superoxide dismutase 1 (SOD1), lipid hydroperoxides (LOOH), nitric oxide metabolites (NOx), malondialdehyde (MDA), and advanced oxidation protein products (AOPP) and computed z unit-weighted composite scores which reflect RONS/NOSTOX. The study included 105 patients with mood disorders, 46 with GAD, and 95 with TUD.Results: MetS was associated with increased levels of MDA and AOPP, independently from mood disorders, TUD, sex and GAD. Atherogenicity and insulin resistance (IR) were significantly associated with a NOSTOX composite score. Mood disorders, TUD, GAD, male sex and MetS independently contribute to increased RONS/NOSTOX. The RONS/NOSTOX profile of MetS was different from that of GAD, which showed increased SOD1 and NOx levels. TUD was accompanied by increased SOD1, LOOH and MDA, and male sex by increased LOOH and AOPP.Conclusions: MetS is characterized by increased lipid peroxidation with aldehyde formation and chlorinative stress, and atherogenicity and IR are strongly mediated by RONS/NOSTOX. Partially shared RONS/NOSTOX pathways underpin the comorbidity of MetS with mood disorders, GAD, and TUD.
ARTICLE | doi:10.20944/preprints202009.0610.v1
Subject: Medicine & Pharmacology, Allergology Keywords: mood disorders; major depression; inflammation; neuro-immune; oxidative stress; nitrosative stress; biomarkers
Online: 25 September 2020 (11:48:43 CEST)
Current diagnoses of mood disorders are not cross validated. The aim of the current paper is to explain how machine learning techniques can be used to a) construct a model which ensembles risk/resilience (R/R), adverse outcome pathways (AOPs), staging, and the phenome of mood disorders, and b) disclose new classes based on these feature sets. This study was conducted using data of 67 healthy controls and 105 mood disordered patients. The R/R ratio, assessed as a combination of the paraoxonase 1 (PON1) gene, PON1 enzymatic activity, and early life time trauma (ELT), predicted the high-density lipoprotein cholesterol – paraoxonase 1 complex (HDL-PON1), reactive oxygen and nitrogen species (RONS), nitro-oxidative stress toxicity (NOSTOX), staging (number of depression and hypomanic episodes and suicidal attempts), and phenome (the Hamilton Depression and Anxiety scores and the Clinical Global Impression; current suicidal ideation; quality of life and disability measurements) scores. Partial Least Squares pathway analysis showed that 44.2% of the variance in the phenome was explained by ELT, RONS/NOSTOX, and staging scores. Cluster analysis conducted on all those feature sets discovered two distinct patient clusters, namely 69.5% of the patients were allocated to a class with high R/R, RONS/NOSTOX, staging, and phenome scores, and 30.5% to a class with increased staging and phenome scores. This classification cut across the bipolar (BP1/BP2) and major depression disorder classification and was more distinctive than the latter classifications. We constructed a nomothetic network model which reunited all features of mood disorders into a mechanistically transdiagnostic model.
ARTICLE | doi:10.20944/preprints202006.0283.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: Metabolic Syndrome; Obesity; inflammation; Oxidative Stress; nitrosative stress; biomarkers
Online: 23 June 2020 (11:35:38 CEST)
Purpose: To investigate the alterations in nitro-oxidative stress (OS) and antioxidant status in adolescents with metabolic syndrome (MetS) and whether these alterations occur independently from effects of overweight or obesity.Methods: Blood was collected in 47 adolescents with MetS and 94 adolescents without MetS as assessed with the International Diabetes Federation criteria. The International Obesity Task Force (IOTF) criteria were used to classify the subjects into those with overweight or obesity. We measured nitro-oxidative biomarkers including nitric oxide metabolites (NOx), lipid hydroperoxides (LOOH), and malondialdehyde (MDA), and antioxidant biomarkers, i.e. total radical-trapping antioxidant parameter (TRAP), paraoxonase (PON)-1 activity, thiol (SH-) groups, as well as tumor necrosis factor-α, glucose, insulin, triglycerides, uric acid and high-density lipoprotein cholesterol (HDL-C).Results: Logistic regression analysis showed that increased MDA and NOx and a lowered TRAP/uric acid ratio were associated with MetS. Machine learning including soft independent modeling of class analogy (SIMCA) showed that the top-3 most important features of MetS were increased glucose and MDA and lowered HDL-C. Support vector machine using MDA, glucose, insulin, HDL-C, triglycerides and body mass index as input variables yielded a 10-fold cross-validated accuracy of 89.8% when discriminating MetS from controls. The association between MetS and increased MDA was independent from the effects of overweight-obesity. glucose, insulin, triglycerides and HDL-C.Conclusion: In adolescents, increased MDA formation is a key component of MetS, indicating that increased production of reactive oxygen species with consequent lipid peroxidation and aldehyde formation participate in the development of MetS.
ARTICLE | doi:10.20944/preprints202001.0285.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: oxidative stress; neuroimmunomodulation; major depression; inflammation; neurotoxicity; schizophrenia
Online: 24 January 2020 (14:46:17 CET)
Oxidative stress toxicity (OSTOX), as well as lowered antioxidant defenses (ANTIOX), play a role in temporal lobe epilepsy (TLE). Nevertheless, the associations between OSTOX/ANTIOX and psychiatric comorbidities in TLE are largely unknown.Thus, this study examines plasma malondialdehyde (MDA), lipid hydroperoxides (LOOH), advanced oxidation protein products (AOPP), nitric oxide metabolites (NOx), total radical trapping antioxidant parameter (TRAP) and sulfhydryl (-SH) groups in Depression due to TLE (n=25); Anxiety Disorders due to TLE (n=27); Psychotic Disorder due to TLE (n=25); “pure TLE” (n=27); and healthy controls (n=40).TLE and mesial temporal sclerosis (MTS) were characterized by significant increases in OSTOX (MDA, AOPP, LOOH) and lowered ANTIOX (-SH groups, TRAP). The discrimination of pure TLE from controls yielded a significant area under the ROC curve for MDA (0.999), AOPP (0.851), -SH groups (0.899) and the OSTOX/ANTIOX ratio (0.996). Seizure frequency is significantly associated with increased MDA and lowered LOOH and NOx levels. Increased MDA was associated with the severity of depressive and physiosomatic symptoms, whilst increased AOPP levels predicted suicidal ideation. Depression and anxiety disorders co-occurring with TLE showed significantly lower MDA levels than TLE without any comorbidities. The psychotic and negative symptoms of TLE are associated with increased MDA levels and excitation with increased LOOH and lowered TRAP levels.These results indicate that oxidative stress toxicity especially protein oxidation and aldehyde formation coupled with lowered -SH groups play a key role in the pathophysiology of TLE/MTS. Increased aldehyde formation also impacts psychopathology, psychosis, as well as negative and depressive symptoms.