Patients with posttraumatic stress disorder exhibit an altered phenotype of regulatory T cells

Jergović, Mladen; Bendelja, Krešo; Vidović, Anđelko; Savić, Ana; Vojvoda, Valerija; Aberle, Neda; Rabatić, Sabina; Jovanović, Tanja; Sabioncello, Ante

doi:10.1186/1710-1492-10-43

Cited by 41 publications

(36 citation statements)

References 52 publications

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“…Consistent with this hypothesis, studies in rats show that glucocorticoids decrease IgA (which normally inhibits bacterial adherence to intestinal epithelial cells), increase bacterial adherence over two-fold, and increase bacterial translocation to mesenteric lymph nodes (98). Decreased immunoregulation, as evidenced by decreased frequency of Treg cells, or altered Treg function, may lead to overactive host immune defenses, increased gut permeability, colitis, and exaggerated PTSD symptoms following trauma exposure (11, 12, 14, 22, 23). Based on the current study, decreases in the relative abundances of Actinobacteria, Lentisphaerae, and Verrucomicrobia (including the prevalent human commensal, A. muciniphila ) may contribute to decreased immunoregulation in PTSD.…”

Section: Discussionmentioning

confidence: 99%

“…Consistent with these findings, genome-wide association studies in PTSD cohorts revealed association with ANKRD55 (16), a gene associated with several autoimmune and inflammatory disorders, including multiple sclerosis (17, 18), type 2 diabetes mellitus (19), celiac disease (20), and rheumatoid arthritis (21). Additionally, Jergovic et al (22, 23) observed an altered Treg phenotype in male combat veterans with PTSD compared to healthy controls. PTSD has also been found to result in upregulation of interleukin (IL) 6 and proinflammatory cytokines, including interferon gamma (IFN-γ), IL-1β and tumor necrosis factor (TNF) (24–26).…”

Section: Introductionmentioning

confidence: 99%

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The Microbiome in Posttraumatic Stress Disorder and Trauma-Exposed Controls: An Exploratory Study

Malan‐Müller²,

et al. 2017

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Objective Inadequate immunoregulation and elevated inflammation may be risk factors for posttraumatic stress disorder (PTSD), and microbial inputs are important determinants of immunoregulation; however, the association between the gut microbiota and PTSD is unknown. This study investigated the gut microbiome in a South African sample of PTSD-affected individuals and trauma-exposed (TE) controls, to identify potential differences in microbial diversity or microbial community structure. Methods The Clinician Administered Posttraumatic Stress Disorder Scale for DSM-5 (CAPS-5) was used to diagnose PTSD according to DSM-5 criteria. Microbial DNA was extracted from stool samples obtained from 18 individuals with PTSD and 12 TE control participants. Bacterial 16S ribosomal RNA (rRNA) gene V3/V4 amplicons were generated and sequenced. Microbial community structure, alpha-diversity, and beta-diversity were analyzed; random forest analysis was used to identify associations between bacterial taxa and PTSD. Results There were no differences between PTSD and TE control groups in alpha- or beta-diversity measures (e.g., alpha-diversity, Shannon index, t = 0.386, P = .70; beta diversity, based on analysis of similarities (ANOSIM), Bray Curtis test statistic = −0.033, P = .70); however, random forests analysis highlighted three phyla as important to distinguish PTSD status: Actinobacteria, Lentisphaerae, and Verrucomicrobia. Decreased total abundance of these taxa was associated with higher PTSD CAPS scores (r = −.387, P = .035). Conclusions In this exploratory study, measures of overall microbial diversity were similar among individuals with PTSD and TE controls; however, decreased total abundance of Actinobacteria, Lentisphaerae, and Verrucomicrobia was associated with PTSD status.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Microbiome in Posttraumatic Stress Disorder and Trauma-Exposed Controls: An Exploratory Study

Malan‐Müller²,

et al. 2017

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“…Individuals with PTSD also exhibit increases in total PBMCs, pro-inflammatory Th1 and Th17 cells, and decreased T-regulatory (T-reg) cells that are correlated with increased peripheral concentrations of IFN-γ and IL-17 (Zhou et al, 2014). Because T-reg cells are critical for containing pro-inflammatory responses and Th1 and Th17 cells activate inflammatory responses (Afzali et al, 2007), these alterations in the composition of T-cell subsets may act in aggregate to direct systemic inflammatory tone into an overdrive state in PTSD (Jergovic et al, 2014). Finally, immunological aging of T-cell phenotypes has also been associated with PTSD (Aiello et al, 2016).…”

Section: Ptsd and Inflammationmentioning

confidence: 99%

Inflammation in Fear- and Anxiety-Based Disorders: PTSD, GAD, and Beyond

Michopoulos

Powers

Gillespie

et al. 2016

Neuropsychopharmacol

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545

376

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The study of inflammation in fear-and anxiety-based disorders has gained interest as growing literature indicates that proinflammatory markers can directly modulate affective behavior. Indeed, heightened concentrations of inflammatory signals, including cytokines and C-reactive protein, have been described in posttraumatic stress disorder (PTSD), generalized anxiety disorder (GAD), panic disorder (PD), and phobias (agoraphobia, social phobia, etc.). However, not all reports indicate a positive association between inflammation and fear-and anxiety-based symptoms, suggesting that other factors are important in future assessments of inflammation's role in the maintenance of these disorders (ie, sex, co-morbid conditions, types of trauma exposure, and behavioral sources of inflammation). The most parsimonious explanation of increased inflammation in PTSD, GAD, PD, and phobias is via the activation of the stress response and central and peripheral immune cells to release cytokines. Dysregulation of the stress axis in the face of increased sympathetic tone and decreased parasympathetic activity characteristic of anxiety disorders could further augment inflammation and contribute to increased symptoms by having direct effects on brain regions critical for the regulation of fear and anxiety (such as the prefrontal cortex, insula, amygdala, and hippocampus). Taken together, the available data suggest that targeting inflammation may serve as a potential therapeutic target for treating these fear-and anxiety-based disorders in the future. However, the field must continue to characterize the specific role pro-inflammatory signaling in the maintenance of these unique psychiatric conditions.

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“…A high proportion of those subdivided into the under-diagnosed asthma group (35.1%) reported symptoms of PTSD, which may account for their shortness of breath or coughing at night (paroxysmal nocturnal dyspnea, wheeze and cough). It is plausible because individuals with PTSD exhibit an altered phenotype of regulatory T cells (12) and furthermore, it has been suggested that asthma onset can be linked to family/personal disasters (13) which is the case in these shelter dwellers (loss of home and/or family member).There are also other adverse factors in shelter living. For example, cooking in the same room where the family lives may increase the exposure to particulate matters (PM 2.5 ) which can exacerbate asthma (14).…”

Section: Discussionmentioning

confidence: 99%

Uncontrolled and under-diagnosed asthma in a Damascus shelter during the Syrian crisis

et al. 2017

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Background: Studies have shown that poor shelter or dwelling conditions may lead to deteriorations in health. Those with asthma may be more susceptible to compromised living conditions and stress leading to a higher risk of asthma exacerbations. To describe the asthma control and quality of life of individuals with diagnosed asthma living in a shelter in Damascus, Syria and estimate the prevalence of respiratory symptoms in shelter dwellers without diagnosed asthma. Methods:In this cross-sectional study, all individuals 5 years and older living in Al-Herjalleh shelter with diagnosed asthma were recruited to complete a questionnaire, which included items related to their respiratory symptoms, asthma exacerbations, exposure to asthma triggers, medication use, and health-related quality of life before and since entering the shelter. A representative sample of shelter dwellers without diagnosed asthma also completed a questionnaire to establish their demographics, respiratory symptoms, environment and chronic disease co-morbidities, in order to identify factors associated with under-diagnosed asthma. All participants underwent spirometry to measure their lung function. Descriptive statistics were calculated, and chi-square tests and Student's t-tests were used to compare individuals with asthma before and since entering the shelter, as well as to compare those with under-diagnosed asthma and individuals without asthma.Results: The prevalence of asthma at the Al-Herjalleh shelter in those aged 5 years and older was approximately 8.5%. Nearly 70% of the asthma group felt their asthma had worsened since entering the shelter, and there was a significant drop in the proportion of individuals using inhaled corticosteroids (ICS), with only 4.3% using daily ICS in the shelter (P<0.0001). The proportion of individuals experiencing a severe asthma attack did not change after entering the shelter (P=0.97), but almost all individuals with asthma (94.4%) reported worsening in their health-related quality of life. In the non-asthma group, 44.2% of participants reported episodes of wheezing, coughing and breathlessness at night, consistent with underdiagnosed asthma. A higher proportion of those with under-diagnosed asthma had allergic rhinitis (57.1%), symptoms of post-traumatic stress disorder (PTSD) (35.1%), and abnormal spirometry (60.0%), compared to those without asthma. Conclusions:The findings of our study highlight the need for asthma programs in Syrian shelters as significant gaps exist in both the screening and management of chronic respiratory diseases to minimize asthma deterioration in Syrian shelter dwellers.

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Patients with posttraumatic stress disorder exhibit an altered phenotype of regulatory T cells

Cited by 41 publications

References 52 publications

The Microbiome in Posttraumatic Stress Disorder and Trauma-Exposed Controls: An Exploratory Study

The Microbiome in Posttraumatic Stress Disorder and Trauma-Exposed Controls: An Exploratory Study

Inflammation in Fear- and Anxiety-Based Disorders: PTSD, GAD, and Beyond

Uncontrolled and under-diagnosed asthma in a Damascus shelter during the Syrian crisis

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