scholarly journals Inflammatory versus Anti-Inflammatory Profiles in Major Depressive Disorders—The Role of IL-17, IL-21, IL-23, IL-35 and Foxp3

2021 ◽  
Vol 11 (2) ◽  
pp. 66
Author(s):  
Małgorzata Gałecka ◽  
Katarzyna Bliźniewska-Kowalska ◽  
Agata Orzechowska ◽  
Janusz Szemraj ◽  
Michael Maes ◽  
...  

Background: The authors of this research study intended to verify whether there are any changes in gene expression in depressed patients without coexisting inflammatory diseases for selected immune-inflammatory factors that are particularly important in autoimmune disease pathogenesis (IL-17, IL-21, IL-23, IL-35, Foxp3). Methods: The study was carried out on a group of 190 patients with depression and 100 healthy volunteers. The severity of depressive symptoms was assessed using the Hamilton Depression Scale. RT-PCR was used to evaluate mRNA expression and ELISA was used to measure protein expression of these genes. Results: The level of gene expression for IL-17, IL-21, IL-23, and IL-35 was substantially higher in the group of patients with depression compared to the control group. The mean mRNA expression of Foxp3 was considerably reduced in patients suffering from depressive disorders. There was a statistically significant correlation between the number of hospitalizations and the expression of specific inflammatory factors. Conclusions: Expression of specific inflammatory genes may be a factor in the etiopathogenesis of depressive disorders. The duration of the disease seems to be more important for the expression of the genes in question than the severity of depression. These cytokines may affect the metabolism of neurotransmitters and neuroendocrine functions in the brain as well as be a marker and a new potential therapeutic target for recurrent depressive disorders.

2021 ◽  
Vol 11 (7) ◽  
pp. 637
Author(s):  
Aleksandra Skiba ◽  
Monika Talarowska ◽  
Janusz Szemraj ◽  
Piotr Gałecki

Aim: Due to the fact that NRXN1 is associated with neurodevelopmental disorders, the aim of this study was to investigate the role of the NRXN1 gene in the etiology and epigenetics of depression by comparison of NRXN1 mRNA expression and NRXN1 protein level expression in patients suffering from depression versus healthy controls, as well as to search for clinical variables related to expression of the analyzed gene. Material and Methods: A total of 180 people aged 19–64 qualified for the study. The experimental group consisted of 97 people who were psychiatrically hospitalized, diagnosed with recurrent depressive disorders (F33) or who met the diagnostic criteria of a depressive episode (F32) according to ICD-10. The control group included 83 healthy people who volunteered to participate in the study. A sample of peripheral blood was obtained from people who were positively qualified to participate in the study—twice in the experimental group and once in the control group for genetic testing. Sociodemographic variables and data on the course of the disorder were also gathered. Patients were examined on study entry and at the end of the hospitalization with the Hamilton Depression Scale. Obtained data were analyzed statistically. The study was approved by the University’s Bioethics Committee. Results: The gene expression of NRXN1 at both mRNA and protein level significantly differs and it is lower in the experimental group compared to expression in healthy people. The difference in gene expression of NRXN1 at both the mRNA and protein levels between the first and second measurement in the experimental group is also significant. The result demonstrates a higher expression level in the first measurement and lower expression level in the second measurement when reported depression symptoms are less severe. Conclusions: Results concerning expression of NRXN1 may play an important role in further researches about the etiopathogenesis of depressive disorders such as looking for depression biomarkers and identifying evidence which may be relevant to personalize treatment for depression.


2021 ◽  
Vol 12 ◽  
Author(s):  
Xiang Gao ◽  
Zuoli Sun ◽  
Guangwei Ma ◽  
Yuhong Li ◽  
Min Liu ◽  
...  

Background: Recent literature suggests that α-Klotho, a widely recognized anti-aging protein, is involved in longevity as well as in many diseases, including Alzheimer's disease, and depression. Although the Klotho gene encodes α-Klotho, a single transmembrane protein with intracellular and extracellular domains, the relationship between Klotho gene polymorphism and circulating α-Klotho levels in patients with major depressive disorder (MDD) is not clear.Methods: A total of 144 MDD patients and 112 age-matched healthy controls were included in this study. The Klotho genetic polymorphisms (rs9536314, rs9527025, and rs9315202) and plasma α-Klotho levels were measured by PCR and ELISA, respectively. The severity of depressive symptoms was estimated using the Hamilton Depression Scale (HAMD).Results: We found a significantly lower level of plasma α-Klotho in the MDD patients than in controls. Among them, only elderly MDD patients (first episode) showed significantly lower α-Klotho levels than the age-matched controls, while elderly recurrent and young MDD patients showed no difference in plasma α-Klotho levels from age-matched controls. The young MDD group showed a significantly earlier onset age, higher plasma α-Klotho levels, and lower HAMD scores than those in the elderly MDD group. While the plasma α-Klotho levels were higher in rs9315202 T alleles carrier regardless age or sex, the rs9315202 T allele was negatively correlated with disease severity only in the elderly MDD patients.Conclusion: The results of our study showed that only elderly MDD patients showed a decrease in plasma α-Klotho levels along with an increase in disease severity as well as an association with the number of rs9315202 T alleles, and not young MDD patients compared to age-matched controls. Our data suggest that circulating α-Klotho levels combined with Klotho genetic polymorphisms are important in elderly MDD patients, particularly carriers of the Klotho gene rs9315202 T allele.


Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Rico Krämer ◽  
Stephan Köhler

Abstract Background Patients with mild to moderate depressive symptoms can have limited access to regular treatment; to ensure appropriate care, low-threshold treatment is needed. Effective online interventions could increase the supply of low-threshold treatment. Further research is needed to evaluate the effectiveness of online interventions. This study aims to evaluate the online-based self-help programme “Selfapy” on a sample of depressive subjects and compares the impact of the programme’s unaccompanied version with its therapeutic accompanied version. Methods A sample of 400 subjects that have a mild to severe depressive episode (Becks Depression Inventory - II and Hamilton Depression Scale) will be used. Subjects are randomly assigned to immediate access to an unaccompanied course (no support from psychologist via weekly phone calls), immediate access to an accompanied course (support from a psychologist via weekly phone calls) or a waiting list control group (access to the intervention after 24 weeks). The intervention will last for a period of 12 weeks. Depressive symptoms as a primary parameter, as well as various secondary parameters, such as life satisfaction, therapeutic relationships, social activation, self-esteem, attitudes towards Internet interventions and drop-out rates, are recorded at four different points in time: at baseline (T1), 6 weeks after the start of the intervention (T2), 12 weeks after the start of the intervention (T3) and 3 months after completion of the treatment follow-up (T4). Conclusion This randomized and controlled, blinded study will make use of a “dismantled” approach to adequately compare the accompanied and unaccompanied versions of the intervention. Positive and meaningful results are expected that could influence the acceptance and implementation of online interventions. Trial registration German Clinical Trials Register DRKS00017191. Registered on 14 June 2019


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1114.2-1114
Author(s):  
M. Letaeva ◽  
M. Koroleva ◽  
J. Averkieva ◽  
O. Malyshenko ◽  
T. Raskina

Objectives:to assess the frequency of occurrence of the anxiety-depressive spectrum in patients with rheumatoid arthritis and ankylosing spondylitis.Methods:A survey was conducted of 44 patients aged from 21 to 57 years (average age - 42.3 ± 6.7 years), who were treated at GAUZ KO OKGVV. All patients had a verified diagnosis of RA and AS according to the ACR criteria and received treatment with basic drugs. The control group consisted of 40 people comparable in age and sex, without concomitant pathology of RA and AS.The depression screening card, the subjective well-being scale, and the hospital anxiety and depression scale (HADS) were used to assess and detect anxiety-depressive syndrome. The assessment of the condition is carried out over the last 2 weeks, which corresponds to the temporary diagnostic criterion for depression.The Depression Screening Scale is a 35-item self-questionnaire that assesses 7 categories of signs: sleep and appetite disorders, anxiety, emotional instability, cognitive impairment, loss of self, guilt, and suicidal tendencies. A total score of 65 and above indicates a high likelihood of depression.The Subjective Well-Being Scale is a psychodiagnostic screening tool for measuring the emotional component of subjective well-being or emotional comfort.Hospital Anxiety and Depression Scale Zigmond A.S., Snaith R.P. was developed for the primary detection of depression and anxiety in a general medical practice. The HADS scale consists of 14 statements with 4 possible answers and includes two parts: anxiety and depression. The sum of points of 8 or more is regarded as “subclinically expressed anxiety / depression”, 11 or more points - “clinically expressed anxiety / depression”.Results:According to the results of the depression screening questionnaire, 34 (77.3%) patients with RA and AS showed signs of depression, while in the control group only 6 (15%) patients tested positive for the presence of depressive disorders. According to the data obtained when assessing the scale of well-being in the main group, 26 (59.1%) patients showed signs of emotional discomfort (the indicator was 80% or more), in the control group - in 6 (15%). Using the hospital scale of anxiety and depression HADS, anxiety-depressive syndrome was detected in 36 (81.8%) patients with RA and AS: 16 (44.4%) patients had anxiety, 20 (55.6%) - depression, of them, subclinically expressed anxiety and depression were observed in 10 (27.7%) and 12 (33.3%) people, respectively. Anxiety-depressive syndrome in the control group, according to the HADS questionnaire, was detected only in 8 (20%) patients, of whom 4 (10%) patients had subclinical anxiety and 4 (10%) had signs of depression. No clinically pronounced anxiety and depression were registered in the control group.Conclusion:In most patients with rheumatoid arthritis and ankylosing spondylitis, anxiety-depressive disorders have been identified, which can directly affect both the course of the disease itself and the development of various complications. Timely diagnosis of mental disorders and close cooperation of rheumatologists, psychiatrists and psychologists in the selection of adequate therapy can improve the course and prognosis of the disease.Disclosure of Interests:None declared


Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Anyu Zhou ◽  
Ning Jinag ◽  
Marco Denegri ◽  
An Xie ◽  
Guangbin Shi ◽  
...  

Objectives: To discover the role of altered gene expression regulation in Brugada Syndrome (BrS) and to find biomarkers for BrS diagnosis. Methods: Twenty-five control patients (Control), 25 BrS patients without SCN5A mutation (SCN5A(-)) and 20 BrS patients with SCN5A mutation (SCN5A(+)) were included in this study. Specified gene expression of white blood cells (WBC) were measured by RT-qPCR using TaqMan® Gene Expression assay. Results: MEF2C and MESP1 are the two major cardiac specific transcription factors expressed in WBC. The mRNA expression levels of SCN5A, MEF2C and HuR, one of mRNA stabilizers, were decreased in the SCN5A (+) group (P=0.047, 0.02, 0.000 vs. control group, respectively). The mRNA expression of MESP1 in WBCs was significantly lower in both SCN5A(-) (P=0.012 vs. control) and SCN5A(+) (P=0.000 vs. control) groups. There was no difference between the two BrS groups in MESP1 expression (P=0.215). The area under the Receiver Operating Characteristics (ROC) analysis curve for prediction of BrS using MESP1 levels was 0.775 (95% CI 0.668, 0.882, asymptotic Sig.=0.000). At the optimal cutoff, the corresponding maximum sensitivity and specificity were 0.62 (95% CI: 0.47, 0.76) and 0.88 (0.69, 0.97), respectively. The diagnostic odds ratio (DOR) of MESP1 for BrS diagnosis was 11.96 (95% CI: 5.79, 24.73). The assessment of the mRNA levels in blood SCN5A, MEF2C and HuR were useful for predicting BrS patients with an SCN5A mutation. The area under the ROC analysis curve for prediction of BrS with an SCN5A mutation using SCN5A, MEF2C and HuR mRNA levels in WBCs was 0.847 (95% CI 0.752, 0.942, asymptotic Sig.=0.000), 0.685 (95% CI 0.542, 0.828, asymptotic Sig.=0.016) and 0.777 (95% CI 0.652, 0.902, asymptotic Sig.=0.000), respectively. At the optimal cutoff, the DOR of SCN5A, MEF2C and HuR for SCN5A(+) BrS diagnosis was 17.5 (95% CI: 8.06, 37.86), 4.9 (95% CI: 2.61, 9.17) and 23.5 (95% CI: 9.39, 58.80), respectively. Conclusions: Our results suggest that assessment of circulating MESP1 may be used as a biomarker for BrS diagnosis while decreased SCN5A, MEF2C and HuR mRNA in WBCs is associated with BrS patients with an SCN5A mutation. Our results also suggest that decreased expression of SCN5A, MEF2C, MESP1, and HuR may be pathophysiologically related to BrS.


2022 ◽  
Author(s):  
Laura Robrahn ◽  
Aline Dupont ◽  
Sandra Jumpertz ◽  
Kaiyi Zhang ◽  
Christian H. Holland ◽  
...  

The hypoxia-inducible transcription factor 1 (HIF-1) has been shown to enhance microbial killing and to ameliorate the course of bacterial infections. While the impact of HIF-1 on inflammatory diseases of the gut has been studied intensively, its function in bacterial infections of the gastrointestinal tract remains largely elusive. With the help of a publicly available gene expression data set, we could infer significant activation of HIF-1 after oral infection of mice with Salmonella Typhimurium. Immunohistochemistry and western blot analysis confirmed marked HIF-1α protein stabilization, especially in the intestinal epithelium. This prompted us to analyze conditional Hif1a -deficient mice to examine cell type-specific functions of HIF-1 in this model. Our results demonstrate enhanced non-canonical induction of HIF-1 activity upon Salmonella infection in the intestinal epithelium as well as in macrophages. Surprisingly, Hif1a deletion in intestinal epithelial cells did not impact on inflammatory gene expression, bacterial spread or disease outcome. In contrast, Hif1a deletion in myeloid cells enhanced intestinal Cxcl2 expression and reduced the cecal Salmonella load. In vitro , HIF-1α-deficient macrophages showed an overall impaired transcription of mRNA encoding pro-inflammatory factors, however, intracellular survival of Salmonella was not impacted by HIF-1α deficiency.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
H R Helmi ◽  
A P Sunjaya ◽  
D Limanan ◽  
A R Prijanti ◽  
S W A Jusman ◽  
...  

Abstract Background Apelin, an adipokine peptide and its receptor has recently emerged as a key signaling pathway in maintaining cardiac performance at chronic pressure loads. Apelin has been linked to ventricular dysfunction and therefore maybe of pathophysiologic relevance as a candidate biomarker in HF patients. Purpose This study aims to investigate Apelin-13 gene expression and level, and Apelin receptor (APJ) level in a rat model of heart failure induced by chronic systemic hypoxia and their correlation to BNP-45 gene expression and level, the current gold standard biomarker for heart failure, and to cardiac histopathologic changes. The effect of chronic systemic hypoxia on cardiac hypertrophy, remodeling and heart failure parameters is also of interest. Methods Twenty-eight male Sprague-Dawley rats (8–12 weeks of age) were placed in special hypoxic chambers divided into 7 groups – a control group provided with normoxia (atmospheric O2 levels) and 6 exposure groups exposed to hypoxia (8% O2) for 6 hours, 1, 3, 5, 7 and 14 days respectively prior to measurement. Changes in the expression of Apelin and BNP-45 were measured using quantitative real-time PCR, whereas changes in Apelin-13, APJ and BNP-45 levels were measured using ELISA. Histopathology staining using Hematoxylin and Eosin was performed on cardiac tissues post-termination. Results Compared to control, BNP-45 mRNA expression in the hypoxic heart was only significantly different in day 14, whereas, Apelin mRNA expression had showed significantly higher values starting from day 7 onward. This is in line with the evidence of cardiac hypertrophy based on histopathologic examination present from day 7 onwards. BNP-45 and Apelin-13 levels were significantly higher compared to control from day 5 onwards with a peak on day 7. Although significantly higher than control, Apelin-13 and BNP-45 level decreases in day 14 as compared to day 7. Mean APJ levels showed a similar profile with Apelin-13 and BNP-45 levels with a peak in day 7 (4.619 ng/mL). The cardiac Apelin-13 level shows strong significant correlation with BNP-45 levels (r 0.823, p-value 0.0001). There was also a strong significant correlation between APJ receptor levels with Apelin-13 (r 0.9029, p-value 0.001) and BNP-45 (r 0.9062, p-value 0.0009) levels. Apelin-13, APJ and BNP-45 levels also showed strong significant positive correlation to the duration of hypoxia exposure. Conclusion Chronic (≥5 days) and not acute systemic hypoxia in an experimental rat model leads to increase in Apelin-13, APJ and BNP-45 levels. Apelin-13 and BNP-45 were found to significantly increase from 5 days onwards. Apelin mRNA expression was found to show significant increase earlier compared to BNP-45 mRNA expression. Hence, Apelin may serve as a new candidate biomarker for detection of HF due to oxidative stress compared to BNP-45. Exposure to chronic systemic hypoxia can serve as an easily replicable rat model for heart failure. Acknowledgement/Funding Department of Biochemistry and Molecular Biology, Faculty of Medicine, Tarumanagara University, Jakarta, Indonesia


2020 ◽  
Vol 11 (4) ◽  
pp. 908-927
Author(s):  
Susan C Campisi ◽  
Clare Zasowski ◽  
Shailja Shah ◽  
Ashka Shah ◽  
Glyneva Bradley-Ridout ◽  
...  

ABSTRACT There is some evidence indicating that nutrition may have the ability to prevent, treat, and/or influence the severity of depression. The aims of this evidence gap map (EGM) are to provide an overview and to determine evidence gaps in the existing research on micronutrients and their impact on depression among children and adolescents. We conducted a comprehensive search in multiple databases of primary and secondary literature assessing the impact of micronutrients on depression-related outcomes such as unipolar depression, major depressive disorders, dysthymia, acute depression, and mood disorders. Abstracts and full-text articles were dual-screened based on predefined eligibility criteria. A total of 30 primary research publications were included in the EGM. About 47% of included studies focused on late adolescents (15–19 y), ∼40% on early adolescents (10–14 y), and ∼13% on children aged 6–9 y. Among the included studies, 8 studies examined a single micronutrient intervention and 22 studies examined micronutrient concentrations (either intake or serum), and their impact on depression. The most frequently studied micronutrients were vitamin D (n = 8), zinc (n = 8), iron (n = 6), folate (n = 7), and vitamin B-12 (n = 5). More longitudinal studies and trials are needed to determine the role of micronutrients in the etiology and treatment of depression among children and adolescents.


1997 ◽  
Vol 85 (3) ◽  
pp. 811-818 ◽  
Author(s):  
Isao Fukunishi ◽  
Takayuki Aoki ◽  
Takashi Hosaka

This study examined correlations of social support with rated mood states, including depression, for 47 patients with cerebrovascular disease during the chronic poststroke period. After the Structured Clinical Interview for DSM-III–R, four psychological measures, the Zung Self-depression Scale, the Hamilton Depression Scale, Profile of Mood States, and Social Support Scale, were administered. The patients with cerebrovascular disease exhibited significantly more psychiatric disorders, including depression, and had poorer social support than healthy controls. The severity of depression was significantly related to poor social support and particularly to the presence of social support rather than just the perception of poor social support. Depressed patients may also rate their support as poor because they are depressed. For some patients with cerebrovascular disease during the chronic poststroke period, depression may be related to low social support.


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