Brain, Behavior, and Immunity

Although both central and peripheral inflammation have been consistently observed in depression, the relationship between the two remains obscure. Extra-axial immune cells may play a role in mediating the connection between central and peripheral immunity. This study investigates the potential roles of calvarial bone marrow and parameningeal spaces in mediating interactions between central and peripheral immunity in depression. Positron emission tomography was employed to measure regional TSPO ...

Early flow cytometry studies revealed T cell activation in major depressive disorder (MDD) (Maes et al., 1990-1993). MDD is characterised by activation of the immune-inflammatory response system (IRS) and the compensatory immunoregulatory system (CIRS), including deficits in T regulatory (Treg) cells. This study examines the number of cannabinoid type 1 (CB1) and type 2 (CB2) receptor bearing T/B lymphocytes in MDD, and the effects of in vitro cannabidiol (CBD) administration on CB1/CB2. Using f...

The relationship between peripheral and central immunity and how these ultimately may cause depressed behaviour has been the focus of a number of imaging studies conducted with Positron Emission Tomography (PET). These studies aimed at testing the immune-mediated model of depression that proposes a direct effect of peripheral cytokines and immune cells on the brain to elicit a neuroinflammatory response via a leaky blood-brain barrier and ultimately depressive behaviour. However, studies conduct...

Maes et al. (2008) published the first paper demonstrating that major depressive disorder (MDD) is accompanied by abnormalities in the microbiota-gut-brain axis, as evidenced by elevated serum IgM/IgA to lipopolysaccharides (LPS) of Gram-negative bacteria, such as Morganella morganii and Klebsiella Pneumoniae. The latter aberrations, which point to increased gut permeability (leaky gut), are linked to activated neuro-immune and oxidative pathways in MDD. To delineate the profile and composition ...

BackgroundThe increasingly compelling data supporting the involvement of immunobiological mechanisms in Major Depressive Disorder (MDD) might provide some explanation of the variance in this heterogeneous condition. Peripheral blood measures of cytokines and chemokines constitute the bulk of evidence with consistent meta-analytic data implicating raised proinflammatory cytokines such as IL6, IL1{beta} and TNF. Among the potential mechanisms linking immunobiological changes to affective neurobiol...

The first publication demonstrating that major depressive disorder (MDD) is associated with alterations in the gut microbiota appeared in 2008 (Maes et al., 2008). The purpose of the present study is to delineate a) the microbiome signature of the phenome of depression, including suicidal behaviours and cognitive deficits; the effects of adverse childhood experiences (ACE) and recurrence of illness index (ROI) on the microbiome; and the microbiome signature of lowered high-density lipoprotein ch...

Major depressive disorder (MDD) is associated with T cell activation (Maes et al. 1990-1993), but no studies have examined the combined effects of T cell activation and deficits in T regulatory (Treg) cells on the severity of acute phase MDD. Using flow cytometry, we determined the percentage and median fluorescence intensity of CD69, CD71, CD40L, and HLADR-bearing CD3+, CD4+, and CD8+ cells, and cannabinoid type 1 receptor (CB1), CD152 and GARP-bearing CD25+FoxP3 T regulatory (Treg) cells in 30...

BackgroundMajor depression (MDD) is linked to neuro-immune, metabolic, and oxidative stress (NIMETOX) pathways. The gut microbiome may contribute to these pathways via leaky gut and immune-metabolic processes. AimsTo identify gut microbial alterations in MDD and to quantify functional pathways and enzyme gene families and integrate these with the clinical phenome and immune-metabolic biomarkers of MDD. MethodsShotgun metagenomics with taxonomic profiling was performed in MDD versus controls us...

The clinical diagnosis of major depressive disorder (MDD), a heterogeneous disorder, still depends on subjective information in terms of various symptoms regarding mood. Detecting extracellular vesicles (EVs) in blood may result in finding a diagnostic biomarker that reflects the depressive stage of patients with MDD. Here, we report the results on the glycosylation pattern of enriched plasma EVs from patients with MDD and age-matched healthy subjects. In this cohort, the levels of Triticum vulg...

BackgroundMajor depression comprises two discrete subtypes, major (MDMD) and simple (SDMD) dysmood disorder. MDMD, but not SDMD, patients were identified to have highly sensitized cytokine/growth factor networks using stimulated whole blood cultures. However, no information regarding serum cytokines/chemokines/growth factors in SDMD is available. ObjectivesThis case-control study compares 48 serum cytokines/chemokines/growth factors in academic students with SDMD (n=64) and first episode (FE)-S...

BackgroundMajor depressive disorder (MDD) is a neuro-immune-metabolic-oxidative (NIMETOX) disorder. Nevertheless, the effects of alterations in immune responsiveness, oxidative stress, antioxidant defenses, gut-derived short-chain fatty acids (SCFAs), metabolic hormones and adipokines on metabolomic modules and the MDD phenome have remained elusive. MethodsSerum samples from 125 MDD inpatients and 40 healthy controls were analyzed using high-resolution metabolomics assays (liquid chromatography...

BackgroundSystemic inflammation and insomnia often co-occur in patients with depression. However, there is no suitable animal model to investigate the relationship between inflammation, sleep deprivation (SD), and depression. MethodsTo model interactions between insomnia, inflammation, and depression, we developed a novel "two-hit" rodent model of depressive-like behaviors using continuous SD followed by daily lipopolysaccharide (LPS) treatment. Control groups received SD, LPS, or sterile phosp...

BackgroundSevere or recurring major depression is associated with increased adverse childhood experiences (ACEs), heightened atherogenicity, and immune-linked neurotoxicity (INT). Nevertheless, the interconnections among these variables in outpatient of major depression (OMDD) have yet to be determined. ObjectivesDetermine the correlations among INT, atherogenicity, and ACEs in 66 OMDD patients (of whom thirty-three had metabolic syndrome, MetS) and sixty-seven controls (31 of whom had MetS). ...

Omics signatures for psychiatric conditions have been under-investigated. This study aimed to identify serum metabolites associated with symptoms of depression or anxiety in Hispanic/Latino adults and to develop and assess metabolite risk scores (MRSs) of these phenotypes. Using data from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), we conducted a metabolome-wide association study of 768 metabolites with depression and anxiety symptoms. We used two separate assay batches meas...

Depression often co-occurs with physical health conditions, including heart disease, diabetes and obesity. While dysregulation of the immunometabolic system is posited to underpin several of these comorbidities, the course of immunometabolic dysregulation in depression and its impact on structural brain changes linked to the disorder remain poorly understood. Using brain imaging and metabolomics data from the UK Biobank, we comprehensively evaluated cross-sectional and longitudinal immunometabol...

BackgroundA recent hypothesis postulates the existence of an "immune-metabolic depression" (IMD) dimension characterized by metabolic dysregulations. Combining data on metabolomics and depressive symptoms, we aimed to identify depressions associated with an increased risk of adverse metabolic alterations. MethodClustering data were from 1094 individuals with current major depressive disorder and measures of 149 metabolites from a 1H-NMR platform and 30 depressive symptoms (IDS-SR30). Canonical ...

BackgroundMajor depressive disorder (MDD) is characterized by increased T helper (Th)1 polarization, T cell activation (e.g., CD71+ and CD40L+), and cannabinoid receptor type 2 bearing CD20+ B cells; and lower T regulatory (Treg) numbers. AimsTo delineate the effects of adverse childhood experiences (ACEs) and recurrence of illness (ROI) on activated T and CB2-bearing B populations, and Tregs, including FoxP3+CD152+, FoxP3+GARP+, and FoxP3+CB1+ cells. MethodsWe measured ROI, ACEs, the number o...

BackgroundThe pathophysiology of amnestic Mild Cognitive Impairment (aMCI) is largely unknown, although some papers found signs of immune activation. AimsTo assess the cytokine network in aMCI after excluding patients with major depression (MDD) and to examine the immune profiles of quantitative aMCI (qMCI) and distress symptoms of old age (DSOA) scores. MethodsA cross-sectional study was conducted on 61 Thai aMCI participants and 60 healthy old adults (both without MDD). The Bio-Plex Pro huma...

Meteorological factors affect the serotonergic system, potentially influencing SLC6A4 promoter methylation in seasonal affective disorder (SAD). However, studies on how sunlight impacts methylation and modulates SERT activity in this context remain limited. This study aims to investigate the effect of average daily sunshine duration on SLC6A4 promoter methylation in a cohort consisting of both patients with SAD as well as healthy controls (HC). Methylation data were collected from 28 patients wi...

BackgroundMajor depressive disorder (MDD) severely impairs individual health and creates heavy societal burdens. Diagnostic and therapeutic research remains hindered by MDDs marked heterogeneity and the absence of valid biomarkers. As a neuro-immune, metabolic, and oxidative stress (NIMETOX) disorder, MDD exhibits metabolomic signatures as a final common pathway in the Chinese population. ObjectivesTo identify lipidomic profile differences between MDD patients and healthy controls and examine a...