Promoter Methylation of LEP and LEPR before and after Bariatric Surgery: A Cross-Sectional Study.

INTRODUCTION: DNA methylation constitutes one important epigenetic mechanism that regulates gene expression in human cells. With regard to obesity, bariatric surgery-induced weight loss has been associated with promoter methylation changes in several genes. Hyperleptinemia is a characteristic feature of obesity. The underlying regulating mechanisms have not yet been completely elucidated. METHODS: We investigated the methylation of the promoters of the leptin gene (LEP) and the leptin receptor gene (LEPR) as well as leptin expression in pre- and postbariatric surgery patients using a comparative cross-sectional design. RESULTS: Our results revealed significantly higher LEP promoter methylation patterns in prebariatric surgery patients compared to postoperatively. DNA methylation of the LEPR promoter was significantly higher in the postoperative group. Moreover, we found significantly higher leptin serum levels in patients before the bariatric surgery than afterwards. DISCUSSION: These findings strengthen the suggestion that there is an association between LEP expression and LEP methylation in obesity. We suggest that the epigenetic profile of LEP might be influenced by leptin serum levels in the form of a regulating feedback mechanism.

DNA-methylation of the dopamin receptor 2 gene is altered during alcohol withdrawal.

The dopaminergic neurotransmission is known to be of crucial importance in addictive behavior. Epigenetic regulation like methylation of DNA influences the function of dopaminergic transmission. The present study investigated alterations of DNA methylation in the dopamine D2 receptor (DRD2)-gene in patients suffering from alcohol dependence. The study sample consists of 99 alcohol dependent males admitted for alcohol withdrawal treatment and a control group of 33 healthy participants. Blood samples underwent bisulfite sequencing to determine levels of DNA-methylation of the promoter region of the DRD2 gene. Mixed linear modeling was used to test differences between patients and controls, course of methylation during detoxification. While DRD2-gene methylation did not differ significantly between patients and controls, we found a significant increase of DRD2-gene methylation during alcohol withdrawal/early abstinence. Craving, measured with the Obsessive Compulsive Drinking Scale (OCDS), was significantly associated with DRD2-gene methylation. Furthermore, smoking significantly influenced DRD2-gene methylation in both, patients and controls. As in other types of addictive disorders, DRD2-gene methylation is altered during alcohol withdrawal/early abstinence. The findings regarding an association with alcohol craving and tobacco consumption point towards a crucial role of DRD2-gene methylation in the neurobiology of addictive behavior.

Microstructural abnormalities of the posterior thalamic radiation and the mediodorsal thalamic nuclei in females with anorexia nervosa--a voxel based diffusion tensor imaging (DTI) study.

Gray matter abnormalities have been found in anorexia nervosa (AN) in several brain regions. However, little is known about white matter abnormalities under the condition of AN. To comprehensively assess the microstructural integrity of white matter pathways in women with anorexia nervosa, we performed voxel-based Diffusion Tensor Imaging (DTI). 21 women with AN according to DSM-IV criteria (9 of them recovered) and 20 female age-matched healthy control subjects were enrolled in the study. The patients had a mean body mass index of 17.2 kg/m(2) (controls: 19.6 kg/m(2)). High resolution T1 images (MP-RAGE) and DTI were performed on a 3 T Siemens-scanner. Images were pre-processed and analyzed using a modified protocol for DTI in SPM2. Fractional anisotropy (FA) maps were compared using t-tests (p < 0.05, corrected). Compared with controls, AN patients showed bilateral reductions of FA maps in the posterior thalamic radiation which includes the optic radiation, and the left mediodorsal thalamus. Our study is limited by the small sample size and its cross-sectional design. A longitudinal design with the same individuals assessed when acutely ill and recovered is warranted for future studies. For the first time, the findings of our DTI study identified disturbances of associational and commissural fibers in the bilateral occipitotemporal white matter. The results help narrowing the prevailing biological models of AN by suggesting that body image distortion is related to microstructural alterations of white matter tracts connecting the extrastriate visual cortex with other brain regions involved in body perception.

Increased levels of adiponectin and resistin in alcohol dependence--possible link to craving.

Recent studies suggested a role of appetite regulating peptides like leptin and ghrelin in alcohol dependence and particularly in the neurobiology of alcohol craving. Aim of the present study was to investigate alterations of the adipocytokines adiponectin and resistin in alcohol-dependent patients. We analyzed a sample of 88 patients at admission for alcohol detoxification and after 1 week of withdrawal treatment in comparison to 89 healthy controls. Adiponectin and resistin serum levels were measured using commercial ELISA kits. The extent of alcohol craving was obtained using the Obsessive Compulsive Drinking Scale (OCDS). Adiponectin and resistin serum levels were significantly elevated in patients with alcohol dependence at both dates (admission and after 1 week of treatment) compared to healthy controls. Adiponectin decreased significantly during the course of withdrawal (T=3.44, p=0.001) while resistin serum levels showed a slight increase (T=-1.83, p=0.071). In a multivariate approach the extent of alcohol craving was significantly associated with adiponectin but not with resistin serum levels in male patients (Beta=-0.255, p=0.025). Results for female patients were not significant. Our findings provide first evidence for an alteration of the adipocytokines adiponectin and resistin during alcohol withdrawal. Furthermore, adiponectin may be involved in the neurobiology of alcohol craving, possibly via its effects on the hypothalamic circuits.

Role of appetite-regulating peptides in alcohol craving: an analysis in respect to subtypes and different consumption patterns in alcoholism.

BACKGROUND: A role of appetite-regulating peptides like leptin and ghrelin in the neurobiology of alcohol craving has been proposed by several studies. Aim of this analysis was to search for differences regarding an association between these peptides and alcohol craving with respect to different subtypes and beverage consumption patterns in patients with alcohol dependence. METHODS: We analyzed a sample of 188 patients at admission for alcohol detoxification regarding leptin and ghrelin (n=117) serum levels. Craving was measured using the Obsessive Compulsive Drinking Scale (OCDS). Patients were classified according to Lesch's typology of alcohol dependence and according to their preferred type of alcoholic beverage (beer, wine, spirits). RESULTS: Using general linear models to analyze a possible interaction between subtypes and leptin/ghrelin levels with respect to craving, we found a significant positive association for leptin in patients of Lesch's types 1 and 2, and in patients consuming beer or wine. Ghrelin levels showed a significant trend regarding an association with craving in patients of Lesch's type 1. In the other subgroups we found no significant results. CONCLUSIONS: Our findings show that appetite-regulating peptides may be of special importance regarding alcohol craving in subtypes of patients. This may explicate at least in part previous contradictory findings.

Nicotine dependence is associated with compulsive alcohol craving.

AIMS: To investigate a possible association of nicotine dependence and alcohol craving. DESIGN: A prospective cross-sectional study on patients diagnosed with alcohol dependence. SETTING: Detoxification unit of a regional psychiatric hospital. PARTICIPANTS: A total of 127 smoking male patients were included in the study at admission for detoxification from alcohol. MEASUREMENTS: The Fagerström Test for Nicotine Dependence (FTND) was used to assess the severity of nicotine dependence while the Obsessive Compulsive Craving Scale (OCDS) was used to measure alcohol craving. The OCDS was assessed at admission and after 7 days of withdrawal treatment, distinguishing the total score, the obsessive and the compulsive subscale. FINDINGS: Spearman's correlation revealed a significant association between the extent of alcohol craving and the FTND score (day 0, n = 127: OCDS total score r = 0.238, P = 0.007; OCDS compulsive score r = 0.280, P = 0.001; day 7; n = 94: OCDS total score r = 0.212, P = 0.040; OCDS compulsive score r = 0.225, P = 0.029). CONCLUSIONS: The severity of nicotine dependence is associated with higher craving in alcohol-dependent patients. These results point towards shared pathophysiological mechanisms in alcohol craving and nicotine addiction.