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Epigenetic perspective on the role of brain-derived neurotrophic factor in burnout.

ABSTRACT: Brain-derived neurotrophic factor (BDNF) plays a potential role in the neurobiology of burnout, but there are no studies investigating the underlying genetic and epigenetic mechanisms. Our aim is to further explore the role of BDNF in burnout, by focusing on the Val66Met polymorphism and methylation patterns of the BDNF gene and serum BDNF (sBDNF) protein expression. We conducted a cross-sectional study by recruiting 129 individuals (59 with burnout and 70 healthy controls). Participants underwent a clinical interview, psychological assessment and blood sample collection. Polymorphism and DNA methylation were measured on DNA from whole blood, using pyrosequencing and sBDNF levels were measured using ELISA. We found significantly increased methylation of promoter I and IV in the burnout group, which also correlated with burnout symptoms. In addition, DNA methylation of promoter I had a significant negative effect on sBDNF. For DNA methylation of exon IX, we did not find a significant difference between the groups, nor associations with sBDNF. The Val66Met polymorphism neither differed between groups, nor was it associated with sBDNF levels. Finally, we did not observe differences in sBDNF level between the groups. Interestingly, we observed a significant negative association between depressive symptoms and sBDNF levels. The current study is the first to show that BDNF DNA methylation changes might play an important role in downregulation of the BDNF protein levels in burnout. The presence of depressive symptoms might have an additional impact on these changes.

SUBMITTER: Bakusic J

PROVIDER: S-EPMC7573604 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Epigenetic perspective on the role of brain-derived neurotrophic factor in burnout.

Bakusic Jelena J Ghosh Manosij M Polli Andrea A Bekaert Bram B Schaufeli Wilmar W Claes Stephan S Godderis Lode L

Translational psychiatry 20201019 1

Brain-derived neurotrophic factor (BDNF) plays a potential role in the neurobiology of burnout, but there are no studies investigating the underlying genetic and epigenetic mechanisms. Our aim is to further explore the role of BDNF in burnout, by focusing on the Val66Met polymorphism and methylation patterns of the BDNF gene and serum BDNF (sBDNF) protein expression. We conducted a cross-sectional study by recruiting 129 individuals (59 with burnout and 70 healthy controls). Participants underwe ...[more]

PMID: 33077716

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Project description:Several studies have implied a role of brain-derived neurotrophic factor (BDNF) in abdominal pain modulation in irritable bowel syndrome (IBS). The aim of this study was to establish BDNF protein expression in human colonic biopsies and to show variation in IBS compared to controls. BDNF protein and mRNA levels were correlated with IBS symptom severity based on the IBS-symptom severity score (IBS-SSS). Biopsies from the descending colon and IBS-SSS were obtained from 10 controls and 20 IBS patients. Total protein of biopsies was extracted and assessed by ELISA and Western Blot. Total mRNA was extracted and gene expression measured by nCounter analysis. In IBS patients, symptom severity scores ranged from 124 to 486 (mean ± sem: 314.2 ± 21.2, >300 represents severe IBS) while controls ranged from 0 to 72 (mean ± sem: 27.7 ± 9.0, <75 represents healthy subjects, p < 0.001). IBS patients reported significantly more food malabsorption, former abdominal surgery and psychiatric comorbidities. BDNF protein was present in all samples and did not differ between IBS and controls or sex. Subgroup analysis showed that female IBS patients expressed significantly more BDNF mRNA compared to male patients (p < 0.05) and male IBS-D patients had higher IBS symptom severity scores and lower BDNF mRNA and protein levels compared to male controls (p < 0.05). Scatter plot showed a significant negative correlation between IBS-SSS and BDNF mRNA levels in the cohort of male IBS-D patients and their male controls (p < 0.05). We detected a high proportion of gastrointestinal surgery in IBS patients and confirmed food intolerances and psychiatric diseases as common comorbidities. Although in a small sample, we demonstrated that BDNF is detectable in human descending colon, with higher BDNF mRNA levels in female IBS patients compared to males and lower mRNA and protein levels in male IBS-D patients compared to male controls. Further research should be directed toward subgroups of IBS since their etiologies might be different.

Project description:Major depressive disorder (MDD) affects millions of people worldwide and is a leading cause of disability. Several theories have been proposed to explain its pathological mechanisms, and the "neurotrophin hypothesis of depression" involves one of the most relevant pathways. Brain-derived neurotrophic factor (BDNF) is an important neurotrophin, and it has been extensively investigated in both experimental models and clinical studies of MDD. Robust empirical findings have indicated an association between increased BDNF gene expression and peripheral concentration with improved neuronal plasticity and neurogenesis. Additionally, several studies have indicated the blunt expression of BDNF in carriers of the Val66Met gene polymorphism and lower blood BDNF (serum or plasma) levels in depressed individuals. Clinical trials have yielded mixed results with different treatment options, peripheral blood BDNF measurement techniques, and time of observation. Previous meta-analyses of MDD treatment have indicated that antidepressants and electroconvulsive therapy showed higher levels of blood BDNF after treatment but not with physical exercise, psychotherapy, or direct current stimulation. Moreover, the rapid-acting antidepressant ketamine has presented an early increase in blood BDNF concentration. Although evidence has pointed to increased levels of BDNF after antidepressant therapy, several factors, such as heterogeneous results, low sample size, publication bias, and different BDNF measurements (serum or plasma), pose a challenge in the interpretation of the relation between peripheral blood BDNF and MDD. These potential gaps in the literature have not been properly addressed in previous narrative reviews. In this review, current evidence regarding BDNF function, genetics and epigenetics, expression, and results from clinical trials is summarized, putting the literature into a translational perspective on MDD. In general, blood BDNF cannot be recommended for use as a biomarker in clinical practice. Moreover, future studies should expand the evidence with larger samples, use the serum or serum: whole blood concentration of BDNF as a more accurate measure of peripheral BDNF, and compare its change upon different treatment modalities of MDD.

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Epigenetic perspective on the role of brain-derived neurotrophic factor in burnout.

Publications

Epigenetic perspective on the role of brain-derived neurotrophic factor in burnout.

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