Do changes in the BDNF promoter methylation indicate the risk of alcohol relapse?

Heberlein, Annemarie; Büscher, Patricia; Schuster, Rilana; Neyazi, Alexandra; Lichtinghagen, Ralf; Rhein, Mathias; Kornhuber, Johannes; Bleich, Stefan; Frieling, Helge; Hillemacher, Thomas

doi:10.1016/j.euroneuro.2015.08.018

Cited by 34 publications

(22 citation statements)

References 25 publications

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“…PPM1G is a serine/threonine phosphatase, and thus it is plausible that a reduction in the levels of PPM1G in the brain is associated with hyperphosphorylation of various substrates. Finally, DNA methylation of the genes encoding nerve growth factor (NGF) and BDNF was increased and the expression level of these neurotrophic factors was decreased, in the serum of people with alcoholism 148, 149 . NGF signalling is an important contributor to normal CNS function 150 , and, as described above, BDNF has a central role in the stop pathways.…”

Section: Epigenetic Modificationsmentioning

confidence: 99%

Molecular mechanisms underlying alcohol-drinking behaviours

2016

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The main characteristic of alcohol use disorder is the consumption of large quantities of alcohol despite the negative consequences. The transition from the moderate use of alcohol to excessive, uncontrolled alcohol consumption results from neuroadaptations that cause aberrant motivational learning and memory processes. Here, we examine studies that have combined molecular and behavioural approaches in rodents to elucidate the molecular mechanisms that keep the social intake of alcohol in check, which we term ‘stop pathways’, and the neuroadaptations that underlie the transition from moderate to uncontrolled, excessive alcohol intake, which we term ‘go pathways’. We also discuss post-transcriptional, genetic and epigenetic alterations that underlie both types of pathways.

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Section: Epigenetic Modificationsmentioning

confidence: 99%

Molecular mechanisms underlying alcohol-drinking behaviours

2016

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“…Thus, the higher methylation in case of levomethadone administration may result in lower VEGF-serum levels in patients compared to the healthy control-group, which underline the role of growth factors in our previous studies; this indicates adverse effects and endogenous counter-regulating attempt of compensation [14, 20, 31]. In alcohol-dependent patients, we could also observe significantly increased mean methylation rates in the promotor region of another neurotrophine (Brain-derived neurotrophic fact [BDNF]) [28]).…”

Section: Discussionmentioning

confidence: 55%

“…By methylation of cytosines in the context of a CpG in the promotor region of a gene, expression is thought to be downregulated in most cases. Recently, we could already show several epigenetic regulations involved in addiction disorders [28-30]. …”

Section: Introductionmentioning

confidence: 99%

Epigenetic Regulation of the Promotor Region of Vascular Endothelial Growth Factor-A and Nerve Growth Factor in Opioid-Maintained Patients

et al. 2017

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Aims: The nerve growth factor (NGF) and the vascular endothelial growth factor-A (VEGF-A) may be of importance for psychiatric diseases including substance use disorders. The aim of the study was to identify differences in the regulation of both neuropeptides via the DNA-methylation status of the promotor regions of NGF and VEGF-A in different forms of maintenance therapy for opioid dependence and the related stress regulation via the hypothalamic-pituitary-adrenal axis. Methods: We compared methylation levels of opioid-dependent patients receiving treatment with diamorphine (n = 28) or levomethadone (n = 54) and similar levels in a healthy control group (n = 72). Results: There was a significantly higher methylation of VEGF-A in opioid-maintained patients with levomethadone compared to that in the control group (estimated marginal means [EMM] [SE]): 0.036 [0.003] vs. 0.020 [0.003]; p < 0.001). We performed a cluster analysis for NGF, splitting up the results in 4 clusters. We found significant changes in methylation rates of the opioid-maintained patients compared to the controls in cluster I ([EMM] [SE]: 0.064 [0.005] vs. 0.084 [0.006]; p = 0.03), cluster II ([EMM] [SE]: 0.133 [0.013] vs. 0.187 [0.014]; p < 0.001) and cluster III ([EMM] [SE]: 0.190 [0.014] vs. 0.128 [0.016]; p < 0.001). Conclusions: The results are of importance, as they indicate that long-term changes in stress regulation regulated by neurotrophines are a crucial part of the symptomatology of opioid dependence, thus influencing drug consumption and the different forms of opioid-maintenance therapies.

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“…In opioid users, no significant promoter methylation variations of BDNF gene were demonstrated compared to control group, without any history of drug abuse (Kordi-Tamandani, Tajoddini, & Salimi, 2015). In alcohol addiction, a significant decrease in BDNF promoter methylation in exon IV was observed during withdrawal, without modifications in serum BDNF levels (Heberlein et al, 2015). The difficulty with these studies can certainly come from subtle changes commonly observed in DNA methylation levels (typically <5%).…”

Section: Epigenetics In Clinicmentioning

confidence: 97%