Although, staging models gained momentum to stage define affective disorders, no attempts were made to construct mathematical staging models using clinical and biomarker data in patients with major depression and bipolar disorder.The aims of this study were to use clinical and biomarker data to construct statistically-derived staging models, which are associated with early lifetime traumata (ELTs), affective phenomenology and biomarkers.In the current study, 172 subjects participated, 105 with affective disorders (both bipolar and unipolar) and 67 controls. Staging scores were computed by extracting latent vectors (LVs) from clinical data including ELTs, recurring flare ups and suicidal behaviors, outcome data such as disabilities and health-related quality of life (HR-QoL), and paraoxonase (PON)1 actvities and nitro-oxidative stress biomarkers.Recurrence of episodes and suicidal behaviors could reliably be combined into a LV with adequate composite reliability (the “recurrence LV”), which was associated with female sex, the combined effects of multiple ELTs, disabilities, HR-QoL and impairments in cognitive tests. All those factors could be combined into a reliable “ELT-staging LV” which was significantly associated with nitro-oxidative stress biomarkers. A reliable LV could be extracted from serum PON1 activities, recurrent flare ups, disabilities and HR-QoL.Our ELT-staging index scores the severity of a relevant affective dimension, shared by both major depression and bipolar disorder, namely the trajectory from ELTs, a relapsing course and suicidal behaviors to progressive disabilities. Patients were classified into three stages, namely an early stage; a relapse-regression stage; and a suicidal-regression stage. Lowered lipid-associated antioxidant defenses may be a drug target to prevent the transition from the early to the later regression stages.
BACKGROUND: There are some reports that catecholamines and beta-adrenoceptor agonists may suppress some immune functions. OBJECTIVES: The present study was carried out in order to examine the effects of noradrenaline (10-5 M, 10-6 M and 10-7 M), yohimbine (10-5 M, 10-6 M and 10-7 M), an alpha2-adrenoceptor antagonist, and clonidine (105 M, 10-6 M and 10-7 M), an alpha2-adrenoceptor agonist, on the stimulated production of interferon-gamma (IFNgamma), a pro-inflammatory cytokine, and interleukin-10 (IL-10), an immuno-inhibitory cytokine. DESIGN: We measured the in vitro production of IFNgamma and IL-10 by stimulated, diluted whole blood of 16 normal volunteers. The IFNgamma/IL-10 production ratio was computed since this ratio reflects the pro- versus anti-inflammatory capacity of the cultured whole blood. RESULTS: We found that 1) noradrenaline, 10-5 M, 10-6 M, and 10-7 M, significantly suppressed the production of IFNgamma and that noradrenaline, 10-5 M, significantly enhanced the production of IL-10. Clonidine, 10-5 M and 10-7 M, significantly suppressed the production of IFNgamma. Noradrenaline, 10-5 M and 10-6 M, and clonidine, 10-5 M, significantly suppressed the IFNgamma/IL-10 production ratio. There were no significant effects of yohimbine on IFNgamma or IL-10 production. CONCLUSIONS: 1) noradrenaline has significant negative immunoregulatory effects in humans through enhancing the production of IL-10 and suppressing that of IFNgamma; and 2) the suppression of the production of IFNgamma is in part related to alpha2-adrenoceptor activation.
Autism Spectrum Disorder (ASD) is a neurodevelopmental disturbance, diagnosed in early childhood. It is associated with varying degrees of dysfunctional communication and social skills, repetitive and stereotypic behaviors. Regardless of the constant increase in the number of diagnosed patients, there are still no established treatment schemes in global practice. Many children with ASD have allergic symptoms, often in the absence of mast cell (MC) positive tests. Activation of MCs may release molecules related to inflammation and neurotoxicity, which contribute to the pathogenesis of ASD. The aim of the present paper is to enrich the current knowledge regarding the relationship between MCs and ASD by providing PPI network analysis-based data that reveal key molecules and immune pathways associated with MCs in the pathogenesis of autism. Network and enrichment analyzes were performed using receptor information and secreted molecules from activated MCs identified in ASD patients. Our analyses revealed cytokines and key marker molecules for MCs degranulation, molecular pathways of key mediators released during cell degranulation, as well as various receptors. Understanding the relationship between ASD and the activation of MCs, as well as the involved molecules and interactions, is important for elucidating the pathogenesis of ASD and developing effective future treatments for autistic patients by discovering new therapeutic target molecules.
An extensive literature describes the positive impact of dietary phytochemicals on overall health and longevity. Dietary phytochemicals include a large group of non-nutrients compounds from a wide range of plant-derived foods and chemical classes. Over the last decade, remarkable progress has been made to realize that oxidative and nitrosative stress (O&NS) and chronic, low-grade inflammation are major risk factors underlying brain aging. Accumulated data strongly suggest that phytochemicals from fruits, vegetables, herbs, and spices may exert relevant negative immunoregulatory, and/or anti-O&NS activities in the context of brain aging. Despite the translational gap between basic and clinical research, the current understanding of the molecular interactions between phytochemicals and immune-inflammatory and O&NS (IO&NS) pathways could help in designing effective nutritional strategies to delay brain aging and improve cognitive function. This review attempts to summarise recent evidence indicating that specific phytochemicals may act as positive modulators of IO&NS pathways by attenuating pro-inflammatory pathways associated with the age-related redox imbalance that occurs in brain aging. We will also discuss the need to initiate long-term nutrition intervention studies in healthy subjects. Hence, we will highlight crucial aspects that require further study to determine effective physiological concentrations and explore the real impact of dietary phytochemicals in preserving brain health before the onset of symptoms leading to cognitive decline and inflammatory neurodegeneration.
