Neuropsychiatric disorders (i.e., mood disorders and schizophrenia) and inflammation are closely intertwined, and possibly powering each other in a bidirectional loop. Depression facilitates ...inflammatory reactions and inflammation promotes depression and other neuropsychiatric disorders. Patients with neuropsychiatric disorders exhibit all cardinal features of inflammation, including increased circulating levels of inflammatory inducers, activated sensors, and inflammatory mediators targeting all tissues. Inflammation may contribute to the pathophysiology and clinical progression of these disorders. Of note, proinflammatory cytokines modulate mood behavior and cognition by reducing brain monoamine levels, activating neuroendocrine responses, promoting excitotoxicity (increased glutamate levels), and impairing brain plasticity. What are the sources of this chronic inflammation? Increasing evidence indicates that changes in neuroendocrine regulation, metabolism, diet/microbiota, and negative health behaviors are important triggers of inflammation. Finally, recent data indicate that early‐life stress is associated with overt inflammation prior to the development of neuropsychiatric disorders.
Neuropsychiatric disorders (notably, mood disorders and schizophrenia) and inflammation are closely intertwined. Increasing evidence indicates that depression and inflammation are powering each other. This article will present the reader with an overview of the inflammatory phenomenon present in neuropsychiatric disorders, especially in mood disorders and schizophrenia. The review will focus on pre‐clinical and clinical evidence that sterile inflammation may contribute to the pathophysiology and clinical progression of these disorders.
•Interpheron-alpha treatment in patients with chronic medical illness was associated with a reduction in plasma tryptophan levels.•Interferon-alpha treatment was associated with an increase in plasma ...kynurenine levels and kynurenine/tryptophan ratio activity.•Interpheron-alpha treatment was associated with increase in depression symptoms over time.
Dysregulated kynurenine (KYN) pathway has been implicated in the pathophysiology of depression. In this systematic review, we examined the relationship between kynurenine pathway metabolites (KYN, kynurenic acid KYNA, tryptophan TRP, quinolinic acid QUIN, KYN/TRP ratio) and depression symptoms in the context of pro-inflammatory activation and immune response. Out of 5,082 articles, fifteen studies were suitable; ten studies (N = 315 medically ill patients treated with interferon-alpha IFN-α) reported baseline and post-intervention plasma KYN, TRP and KYN/TRP ratios which were included in quantitative meta-analysis. Data from five studies were summarized (IFN-α, interferon-beta IFN-β, and lipopolysaccharide LPS). We found that IFN-α treatment in patients with chronic illnesses was associated with decreased TRP, increased levels of KYN and KYN/TRP ratio and depression scores from baseline to follow-up at both 4 and 24 weeks. Our findings suggest that increased risk of depression observed after immune-activating agents in patients with chronic medical illnesses is likely mediated by the kynurenine pathway. Further prospective studies are required to investigate the exact pathophysiology of the KYN pathway in depression.
Abstract Evidence suggests that maternal and fetal immune dysfunction may impact fetal brain development and could play a role in neurodevelopmental disorders, although the definitive ...pathophysiological mechanisms are still not completely understood. Stress, malnutrition and physical inactivity are three maternal behavioral lifestyle factors that can influence immune and central nervous system (CNS) functions in both the mother and fetus, and may therefore, increase risk for neurodevelopmental/psychiatric disorders. First, we will briefly review some aspects of maternal-fetal immune system interactions and development of immune tolerance. Second, we will discuss the bidirectional communication between the immune system and CNS and the pathways by which immune dysfunction could contribute to neurodevelopmental disorders. Third, we will discuss the effects of prenatal stress and malnutrition (over and undernutrition) on perinatal programming of the CNS and immune system, and how this might influence neurodevelopment. Finally, we will discuss the beneficial impact of physical fitness during pregnancy on the maternal-fetal unit and infant and how regular physical activity and exercise can be an effective buffer against stress- and inflammatory-related disorders. Although regular physical activity has been shown to promote neuroplasticity and an anti-inflammatory state in the adult, there is a paucity of studies evaluating its impact on CNS and immune function during pregnancy. Implementing stress reduction, proper nutrition and ample physical activity during pregnancy and the childbearing period may be an efficient strategy to counteract the impact of maternal stress and malnutrition/obesity on the developing fetus. Such behavioral interventions could have an impact on early development of the CNS and immune system and contribute to the prevention of neurodevelopmental and psychiatric disorders. Further research is needed to elucidate this relationship and the underlying mechanisms of protection. This article is part of a Special Issue entitled SI: Neuroimmunology in Health And Disease.
Eotaxin-1/CCL11 is a chemokine originally implicated in the selective recruitment of eosinophils into inflammatory sites during allergic reactions, being thoroughly investigated in asthma, allergic ...rhinitis, and other eosinophil-related conditions. Eotaxin-1/CCL11 is also involved with a skewed immune response toward a type-2 (Th2) profile. In addition to its role in immune response, recent studies have shown that eotaxin-1/CCL11 is associated with aging, neurogenesis and neurodegeneration, being able to influence neural progenitor cells, and microglia. Increased circulating levels of eotaxin-1/CCL11 have been described in major psychiatric disorders (schizophrenia, bipolar disorder, major depression), sometimes correlating with the severity of psychopathological and cognitive parameters. As similar findings have been reported in neurodegenerative conditions such as Alzheimer's disease, it has been hypothesized that mechanisms involving eotaxin-1/CCL11 signaling may underlie the "accelerated aging" profile commonly linked to psychiatric disorders. Future studies must determine whether eotaxin-1/CCL11 can be regarded as a prognostic biomarker and/or as therapeutic target for resistant/progressive cases.
•Decreased levels of kynurenine was found in unipolar depression vs. healthy controls.•No significant differences were found in tryptophan levels or kynurenine/tryptophan ratios in patients with ...unipolar or bipolar disorder vs. healthy controls.
Activation of the kynurenine pathway is one of the described mechanisms by which inflammation can induce depression. It involves multiple pathways including interference with the bioavailability of tryptophan central to the synthesis of the neurotransmitter serotonin.
In this systematic review, we examine the relationship between kynurenine metabolites (kynurenine, kynurenic acid, tryptophan, quinolinic acid, the ratio of kynurenine and tryptophan) and mood disorders by conducting a meta-analysis.
Fifty-six studies were identified, 21 met inclusion criteria and 14 were deemed suitable (9 investigating unipolar depression and 5 bipolar disorder).
We found decreased levels of kynurenine in unipolar major depression vs. healthy controls but studies were significantly heterogeneous in nature. No significant differences were found in tryptophan levels or kynurenine/tryptophan ratios. Kynurenine metabolites are likely to play a role in major depression but an exact etiological role in mood disorder seem complex and requires further research.
To investigate the effects of squat exercises combined with whole-body vibration on the plasma concentration of inflammatory markers and the functional performance of elderly individuals with knee ...osteoarthritis (OA).
Clinical, prospective, randomized, single-blinded study.
Exercise physiology laboratory.
Elderly subjects with knee OA (N=32) were divided into 3 groups: (1) squat exercises on a vibratory platform (platform group, n=11); (2) squat exercises without vibration (squat group, n=10); and (3) the control group (n=11).
The structured program of squat exercises in the platform and squat groups was conducted 3 times per week, on alternate days, for 12 weeks.
Plasma soluble tumor necrosis factor-α receptors 1 (sTNFR1) and 2 (sTNFR2) were measured using immunoassays (the enzyme-linked immunosorbent assay method). The Western Ontario and McMaster Universities Osteoarthritis Index questionnaire was used to evaluate self-reported physical function, pain, and stiffness. The 6-minute walk test, the Berg Balance Scale, and gait speed were used to evaluate physical function.
In the platform group, there were significant reductions in the plasma concentrations of the inflammatory markers sTNFR1 and sTNFR2 (P<.001 and P<.05, respectively) and self-reported pain (P<.05) compared with the control group, and there was an increase in balance (P<.05) and speed and distance walked (P<.05 and P<.001, respectively). In addition, the platform group walked faster than the squat group (P<.01).
The results suggest that whole-body vibration training improves self-perception of pain, balance, gait quality, and inflammatory markers in elderly subjects with knee OA.
Encephalitis is caused by autoimmune or infectious agents marked by brain inflammation. Investigations have reported altered concentrations of the cytokines in encephalitis. This study was conducted ...to determine the relationship between encephalitis and alterations of cytokine levels in cerebrospinal fluid (CSF) and serum. We found possibly suitable studies by searching PubMed, Embase, Scopus, and Web of Science, systematically from inception to August 2021. 23 articles were included in the meta-analysis. To investigate sources of heterogeneity, subgroup analysis and sensitivity analysis were conducted. The protocol of the study has been registered in PROSPERO with a registration ID of CRD42021289298. A total of 23 met our eligibility criteria to be included in the meta-analysis. A total of 12 cytokines were included in the meta-analysis of CSF concentration. Moreover, 5 cytokines were also included in the serum/plasma concentration meta-analysis. According to the analyses, patients with encephalitis had higher CSF amounts of IL-6, IL-8, IL-10, CXCL10, and TNF-alpha than healthy controls. The alteration in the concentration of IL-2, IL-4, IL-17, CCL2, CXCL9, CXCL13, and IFN-gamma was not significant. In addition, the serum/plasma levels of the TNF-alpha were increased in encephalitis patients, but serum/plasma concentration of the IL-6, IL-10, CXCL10, and CXCL13 remained unchanged. This meta-analysis provides evidence for higher CSF concentrations of IL-6, IL-8, IL-10, CXCL10, and TNF-alpha in encephalitis patients compared to controls. The diagnostic and prognostic value of these cytokines and chemokines should be investigated in future studies.
Long non-coding RNAs (lncRNAs) have been reported to be involved in the pathogenesis of neurodegenerative diseases. It has also been hypothesized that plasma exosomal lncRNAs may be used as ...Alzheimer's disease (AD) biomarkers. In this systematic review, we compiled all studies on the subject to evaluate the accuracy of lncRNAs in identifying AD cases through meta-analysis.
A PRISMA-compliant systematic search was conducted in PubMed/MEDLINE, EMBASE, and Web of Science databases for English publications till September 2022. We included all observational studies published which investigated the sensitivity and specificity of various lncRNAs in plasma samples of AD diagnosis. Our search strategy included lncRNA and all the related spelling and abbreviation variations combined with the keyword Alzheimer's disease. Methodological quality was assessed using the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines and the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-II) tool. The meta-analysis was carried out using the area under the Receiver Operator Characteristic (ROC) curves (AUC) and sensitivity and specificity values to assess the accuracy of the identified lncRNAs in AD diagnosis. To account for the predicted heterogeneity of the study, a random-effects model was used. All the statistical analyses and visualizations were conducted using Stata 17.0 software.
A total of seven studies (AD patients = 553, healthy controls = 513) were included in the meta-analysis. Three lncRNAs were upregulated (RNA BACE-AS1, RNA NEAT1, RNA GAS5), and one lncRNA (MALAT1) was downregulated in plasma samples of AD patients. RNA 51A and RNA BC200 were reported to have variable expression patterns. A lncRNA (RNA 17A) was not significantly different between AD and control groups. The pooled sensitivity, specificity, and AUC values of lncRNAs in identifying AD were (0.74; 95% CI 0.63, 0.82, I2 = 79.2%), (0.88; 95% CI 0.75, 0.94, I2 = 88.9%), and 0.86; 95% CI 0.82, 0.88, respectively. In addition, the pooled diagnostic odds ratio (DOR) of the five individual lncRNAs in AD diagnosis was 20.
lncRNAs had high accuracy in identifying AD and must be seen as a promising diagnostic biomarker of the disease.
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