A study of TNF-α, TGF-β, IL-10, IL-6, and IFN-γ gene polymorphisms in patients with depression

Mihailova, Snezhina; Ivanova-Genova, Elena; Lukanov, Tzvetelin; Stoyanova, В.; Milanova, Vihra; Naumova, Elissaveta

doi:10.1016/j.jneuroim.2016.03.005

Cited by 46 publications

(27 citation statements)

References 43 publications

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“…The resultant relative quantification data indicated a significantly higher level of IL-1β expression in depressed patients compared to healthy controls, suggesting a mildly altered immune activation in the MDD group. However, the present study did not replicate previous findings that have indicated increased gene expression or involvement of IL-6 , IFN-γ , or TNF-α in depression [ 42 , 43 ].…”

Section: Discussioncontrasting

confidence: 99%

Diurnal Hypothalamic-Pituitary-Adrenal Axis Measures and Inflammatory Marker Correlates in Major Depressive Disorder

Doolin

Farrell

Tozzi

et al. 2017

IJMS

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Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and inflammatory systems is a consistent finding in patients with Major Depressive Disorder (MDD). Cortisol is often assessed by measurement of the cortisol awakening response (CAR) and/or diurnal cortisol levels. Some methods of cortisol measurement overestimate cortisol concentration due to detection of other glucocorticoids including the relatively inert cortisone, therefore this study aimed to assess the presence of both cortisol and cortisone, and the cortisol-cortisone catalyzing enzyme 11β-hydroxysteroiddehydrogenase type 1 (11β-HSD1), in depressed patients and controls. Because the HPA axis is known to regulate the body’s immune system, relationships between measures of cytokines and cortisol were also assessed. Saliva samples were collected from 57 MDD patients and 40 healthy controls at five post-wakening time points (0, +30, +60, +720 and +750 min). Glucocorticoid concentrations were measured by liquid chromatography mass spectrometry. Whole blood mRNA expression of several inflammatory markers was measured by quantitative polymerase chain reaction. This study replicated the common finding of elevated morning cortisol and reduced CAR reactivity in MDD and found no differences in cortisone or 11β-HSD1 mRNA measures. There was a negative association between interleukin 1-β (IL-1β) mRNA and morning cortisol reactivity within the depressed group, indicating that dysregulation of the HPA axis and immune system may be interconnected.

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Section: Discussioncontrasting

confidence: 99%

Diurnal Hypothalamic-Pituitary-Adrenal Axis Measures and Inflammatory Marker Correlates in Major Depressive Disorder

Doolin

Farrell

Tozzi

et al. 2017

IJMS

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“…The TGF-β1 itself was first implicated in the pathogenesis of depression when Myint and colleagues 39 found significantly lower levels of this protein in the blood of patients diagnosed with MDD than in the control group. Since then numerous studies have confirmed the connection between MDD and TGF-β 40 – 43 . Studies were able to associate low levels of TGF-β1 with MDD but they have failed to associate TGF-β with suicidal behaviour.…”

Section: Resultsmentioning

confidence: 97%

High-Coverage Whole-Exome Sequencing Identifies Candidate Genes for Suicide in Victims with Major Depressive Disorder

Tombácz

Maróti

Kalmár

et al. 2017

Sci Rep

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We carried out whole-exome ultra-high throughput sequencing in brain samples of suicide victims who had suffered from major depressive disorder and control subjects who had died from other causes. This study aimed to reveal the selective accumulation of rare variants in the coding and the UTR sequences within the genes of suicide victims. We also analysed the potential effect of STR and CNV variations, as well as the infection of the brain with neurovirulent viruses in this behavioural disorder. As a result, we have identified several candidate genes, among others three calcium channel genes that may potentially contribute to completed suicide. We also explored the potential implication of the TGF-β signalling pathway in the pathogenesis of suicidal behaviour. To our best knowledge, this is the first study that uses whole-exome sequencing for the investigation of suicide.

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“…It was found that other SNPs of TGFB1 could be associated with MDD. In the case of rs1800470 (codon 10), genotype T/T is significantly more frequently distributed in depressed patients (Mihailova et al, 2016). Moreover, another study revealed that C/C genotype of the same SNP is positively correlated with higher risk of depression development and more severe episodes of the disease (Caraci et al, 2012).…”

Section: Discussionmentioning

confidence: 98%

Novel association between TGFA, TGFB1, IRF1, PTGS2 and IKBKB single-nucleotide polymorphisms and occurrence, severity and treatment response of major depressive disorder

Białek

Czarny

Watała

et al. 2020

PeerJ

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Background Activation of the immune system might affect the severity of depressive episodes as well as response to the antidepressant treatment. The purpose of this study was to investigate whether the occurrence of variant alleles of analyzed SNPs are involved in prevalence and progression of depression. Moreover, selected genes and SNPs have not been investigated in context of the disease severity and treatment. Therefore, six polymorphisms were selected: g.41354391A>G-TGFB1 (rs1800469), g.132484229C>A-IRF (rs2070729), g.186643058A>G-PTGS2 (rs5275), g.186640617C>T-PTGS2 (rs4648308), g.70677994G>A-TGFA (rs2166975) and g.42140549G>T–IKBKB (rs5029748). Methods A total of 360 (180 patients and 180 controls) DNA samples were genotyped using TaqMan probes. Results We observed that A/G of the rs2166975 TGFA, A/C of rs2070729 IRF1 and G/T of rs5029748 IKBKB were associated with an increased risk of depression development while the T/T of rs5029748 IKBKB, T/T of rs4648308 PTGS2 and G/G of rs2166975 TGFA reduced this risk. We also stratified the study group according to gender and found that genotype A/G and allele G of the rs2166975 TGFA, G/T of rs5029748 IKBKB as well as C allele of rs4648308 PTGS2, homozygote A/A and allele A of rs5275 PTGS2 were associated with increased risk of depression development in men while homozygote G/G of rs5275 PTGS2 decreased this risk. Moreover, C/T of rs4648308 PTGS2 and A/G of rs5275 PTGS2 was positively correlated with the risk of the disease occurrence in women. Furthermore, a gene–gene analysis revealed a link between studied polymorphisms and depression. In addition, A/A of rs1800469 TGFB1 was associated with earlier age of onset of the disease while G/G of this SNP increased severity of the depressive episode. Interestingly, A/C of rs2070729 IRF1 and T/T of rs5029748 IKBKB may modulate the effectiveness of selective serotonin reuptake inhibitors therapy. In conclusion, studied SNPs may modulate the risk of occurrence, age of onset, severity of the disease and response to the antidepressant treatment.

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A study of TNF-α, TGF-β, IL-10, IL-6, and IFN-γ gene polymorphisms in patients with depression

Cited by 46 publications

References 43 publications

Diurnal Hypothalamic-Pituitary-Adrenal Axis Measures and Inflammatory Marker Correlates in Major Depressive Disorder

Diurnal Hypothalamic-Pituitary-Adrenal Axis Measures and Inflammatory Marker Correlates in Major Depressive Disorder

High-Coverage Whole-Exome Sequencing Identifies Candidate Genes for Suicide in Victims with Major Depressive Disorder

Novel association between TGFA, TGFB1, IRF1, PTGS2 and IKBKB single-nucleotide polymorphisms and occurrence, severity and treatment response of major depressive disorder

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