Epigenetic modulation of BDNF gene: Differences in DNA methylation between unipolar and bipolar patients

Dell’Osso, Bernardo; D’Addario, Claudio; Palazzo, Carlotta; Benatti, Beatrice; Camuri, G.; Galimberti, Daniela; Fenoglio, Chiara; Scarpini, Elio; Francesco, Andrea Di; Maccarrone, Mauro; Altamura, A.C.

doi:10.1016/j.jad.2014.05.020

Cited by 91 publications

(55 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The CpG island of the BDNF gene upstream of exon I was found as a possible diagnostic biomarker of MDD (Fuchikami et al 2011), and higher methylation status of the BDNF promoter was associated with MDD (D 'Addario et al 2013;Carlberg et al 2014;Dell'Osso et al 2014;Januar et al 2015) and post-stroke depression ).…”

Section: Gene Methylationmentioning

confidence: 99%

Consensus paper of the WFSBP Task Force on Genetics: Genetics, epigenetics and gene expression markers of major depressive disorder and antidepressant response

Fabbri

Hosák

Mößner

et al. 2016

The World Journal of Biological Psychiatry

View full text Add to dashboard Cite

Major depressive disorder (MDD) is a heritable disease with a heavy personal and socio-economic burden. Antidepressants of different classes are prescribed to treat MDD, but reliable and reproducible markers of efficacy are not available for clinical use. Further complicating treatment, the diagnosis of MDD is not guided by objective criteria, resulting in the risk of under-or overtreatment. A number of markers of MDD and antidepressant response have been investigated at the genetic, epigenetic, gene expression and protein levels. Polymorphisms in genes involved in anti-depressant metabolism (cytochrome P450 isoenzymes), antidepressant transport (ABCB1), glucocorticoid signalling (FKBP5) and serotonin neurotransmission (SLC6A4 and HTR2A) were among those included in the first pharmacogenetic assays that have been tested for clinical applicability. The results of these investigations were encouraging when examining patient-outcome improvement. Furthermore, a nine-serum biomarker panel (including BDNF, cortisol and soluble TNF-a receptor type II) showed good sensitivity and specificity in differentiating between MDD and healthy controls. These first diagnostic and response-predictive tests for MDD provided a source of optimism for future clinical applications. However, such findings should be considered very carefully because their benefit/cost ratio and clinical indications were not clearly demonstrated. Future tests may include combinations of different types of biomarkers and be specific for MDD subtypes or pathological dimensions.

show abstract

Section: Gene Methylationmentioning

confidence: 99%

Consensus paper of the WFSBP Task Force on Genetics: Genetics, epigenetics and gene expression markers of major depressive disorder and antidepressant response

Fabbri

Hosák

Mößner

et al. 2016

The World Journal of Biological Psychiatry

View full text Add to dashboard Cite

show abstract

“…Epigenetic studies in rodents have shown that early life stress resulted in a higher DNA methylation status of BDNF in neuronal tissue (Roth et al, 2009). Moreover, results from clinical studies suggest an involvement of increased BDNF DNA methylation in the etiology of stress-related mental disorders in humans (D'Addario et al, 2012;Dell'Osso et al, 2014;Fuchikami et al, 2011;Kang et al, 2013;Keller et al, 2010;Perroud et al, 2013). Notably, Perroud et al (2013) reported early maltreatment-related changes in BDNF DNA methylation measured in peripheral blood cells.…”

Section: Introductionmentioning

confidence: 99%

Childhood maternal care is associated with DNA methylation of the genes for brain-derived neurotrophic factor (BDNF) and oxytocin receptor (OXTR) in peripheral blood cells in adult men and women

Unternäehrer

Meyer

Burkhardt

et al. 2015

Stress

156

124

View full text Add to dashboard Cite

In adults, reporting low and high maternal care in childhood, we compared DNA methylation in two stress-associated genes (two target sequences in the oxytocin receptor gene, OXTR; one in the brain-derived neurotrophic factor gene, BDNF) in peripheral whole blood, in a cross-sectional study (University of Basel, Switzerland) during 2007-2008. We recruited 89 participants scoring < 27 (n = 47, 36 women) or > 33 (n = 42, 35 women) on the maternal care subscale of the Parental Bonding Instrument (PBI) at a previous assessment of a larger group (N = 709, range PBI maternal care = 0-36, age range = 19-66 years; median 24 years). 85 participants gave blood for DNA methylation analyses (Sequenom(R) EpiTYPER, San Diego, CA) and cell count (Sysmex PocH-100i™, Kobe, Japan). Mixed model statistical analysis showed greater DNA methylation in the low versus high maternal care group, in the BDNF target sequence [Likelihood-Ratio (1) = 4.47; p = 0.035] and in one OXTR target sequence Likelihood-Ratio (1) = 4.33; p = 0.037], but not the second OXTR target sequence [Likelihood-Ratio (1) < 0.001; p = 0.995). Mediation analyses indicated that differential blood cell count did not explain associations between low maternal care and BDNF (estimate = -0.005, 95% CI = -0.025 to 0.015; p = 0.626) or OXTR DNA methylation (estimate = -0.015, 95% CI = -0.038 to 0.008; p = 0.192). Hence, low maternal care in childhood was associated with greater DNA methylation in an OXTR and a BDNF target sequence in blood cells in adulthood. Although the study has limitations (cross-sectional, a wide age range, only three target sequences in two genes studied, small effects, uncertain relevance of changes in blood cells to gene methylation in brain), the findings may indicate components of the epiphenotype from early life stress.

show abstract

“…BDNF promoter hypermethylation was found in mononuclear blood cells from MDD subjects compared to either controls or bipolar patients [29,30]. However, the opposite, hypomethylation of BDNF CpG sites including the promoter region in subjects with MDD, was found in saliva when compared to controls [31].…”

Section: Epigenetic Markersmentioning

confidence: 90%

The Promise of Biomarkers in Diagnosing Major Depression in Primary Care: the Present and Future

Redei¹,

Mehta²

2015

Curr Psychiatry Rep

View full text Add to dashboard Cite

Major depressive disorder (MDD) is the most prevalent psychiatric disorder, but it can be underdiagnosed or misdiagnosed. Most people with depression are seen in primary care settings, where there are limited resources to diagnose and treat the patient. There is a lack of clinically validated objective laboratory-based diagnostic tests to diagnose MDD; however, it is clear that these tests could greatly improve the correct and timely diagnosis. This review aims to give a cross-sectional view of current efforts of DNA methylomic, transcriptomic, and proteomic approaches to identify biomarkers. We outline our view of the biomarker developmental steps from discovery to clinical application. We then propose that better cooperation will lead us closer to the common goal of identifying biological biomarkers for major depression. "The important thing is not to stop questioning. Curiosity has its own reason for existing." Albert Einstein.

show abstract

Epigenetic modulation of BDNF gene: Differences in DNA methylation between unipolar and bipolar patients

Cited by 91 publications

References 19 publications

Consensus paper of the WFSBP Task Force on Genetics: Genetics, epigenetics and gene expression markers of major depressive disorder and antidepressant response

Consensus paper of the WFSBP Task Force on Genetics: Genetics, epigenetics and gene expression markers of major depressive disorder and antidepressant response

Childhood maternal care is associated with DNA methylation of the genes for brain-derived neurotrophic factor (BDNF) and oxytocin receptor (OXTR) in peripheral blood cells in adult men and women

The Promise of Biomarkers in Diagnosing Major Depression in Primary Care: the Present and Future

Contact Info

Product

Resources

About