T. Hillemacher

The epigenetic regulation of GATA4-dependent brain natriuretic peptide expression during alcohol withdrawal

Introduction Natriuretic peptides participate in the complex collection of metabolic effects in reaction to chronic alcohol drinking. Brain natriuretic peptide (BNP) is a specific member of this family known to be expressed in heart and brain. Objectives Having witnessed modulation of other natriuretic peptides in a longitudinal cohort of alcohol-dependent patients undergoing detoxification treatment, we were interested how BNP methylation would be altered in correlation to protein expression and major clinical markers for craving. Aim The epigenetic regulation of BNP in the context of alcoholism is unknown to this date. Methods Ninety-nine male patients were subjected to a longitudinal investigation (days 1, 7 and 14 of detoxification treatment) and compared with 101 healthy controls concerning epigenetic regulation and protein expression of BNP. Results Serum levels of BNP are significantly decreasing during withdrawal. Global OCDS scores are decreasing significantly. Focusing on the two CpGs that are between GATA transcription factor binding sites, detailed statistical analysis reveals a reversely proportional methylation pattern, significantly increasing with ongoing detoxification and thereby supporting the observed serum level changes, accordingly. With BNP expression being GATA4-dependent, we observed a correlation of GATA4 binding site methylation and protein expression during alcohol withdrawal. Conclusion Without the functional knowledge about the crucial regulation of BNP expression via the GATA transcription factor, it would have been easy to take the mean results of the global CpG data and propose a direct relationship between methylation and expression. Thus, these findings are also a voice for functionally and mechanistically approved results.

Auf dem Weg zu biologisch definierten Subtypen

Depressive Störungen sind heterogene Erkrankungen mit sehr unterschiedlichen Symptomkonstellationen. Bislang konnten neben den bekannten Einteilungen nach Schweregrad und Verlaufsform kaum therapierelevante Subtypen der Depression definiert werden oder Studienergebnisse zu einzelnen vorgeschlagenen Subtypen wie etwa der atypischen Depression widersprechen sich.

Alkoholabhängigkeit und Epigenetik

In the last years neurobiological investigations have lead to new insights in the pathophysiological mechanisms underlying addictive behaviour, particularly alcohol dependence. This included results regarding specific changes in the epigenetic regulation, particularly alterations of DNA methylation patterns in specific candidate genes. These studies may help to bridge the gap between genetic and psychosocial/clinical research.

P01-125 - Alcohol-related absence from work and hospital treatment are associated with higher mortality and permanent disability among workers

Aims It was the aim of this study to estimate effects of alcohol abuse on early retirement and premature death in the working population with special emphasis on alcohol related absenteeism from work and inpatient treatment. Methods Sample consisted of 125.019 resp. 128.001 health insurance clients up to age 58 resp. 74 were used. Mean follow-up period was 6.4 years. Excess risks were calculated with Cox regression models adjusted for age, gender, education and job classification. Results Both alcohol-related absenteeism from work (without inpatient treatment) and detoxification treatment were associated with higher risks of early retirement (RR 2.59, CI 2.21–3.04, pxa0 Further analysis showed higher risks of early retirement for males. Females who sought inpatient treatment for alcohol abuse/addiction had the highest risk of premature death (RR 7.75, CI 5.61–10.68, pxa0 Conclusions The detrimental effect of alcoholism on life expectancy and capacity to work is considerable after absenteeism from work, psychiatric treatment and all-cause inpatient treatment. While female patients in detoxification wards are a minority, they may be more strongly affected by the somatic complications of alcohol abuse. Nevertheless, strong selection biases in this subsample need to be considered and the data interpreted with caution.