Methylation of the Oxytocin, Oxytocin Receptor, and Vasopressin Gene Promoters in Tobacco Use Disorder during Cessation.

Introduction: Vasopressin (AVP) and oxytocin (OT) exert sex-specific effects on social pair bonding and stress reactions while also influencing craving in substance use disorders. In this regard, intranasal oxytocin (OT) and AVP antagonists present potential treatments for tobacco use disorder (TUD). Since transcription of both hormones is also regulated by gene methylation, we hypothesized sex-specific changes in methylation levels of the AVP, OT, and OT receptor (OXTR) gene during nicotine withdrawal.

Therapeutic Use of Cannabinoids in Critically Ill Patients: A Survey of Intensive Care Physicians in Germany.

In the course of the legalization of cannabis for therapeutic purposes in Germany, there has been growing interest in the medical use of cannabinoids. To date, the therapeutic potential of cannabinoids for the treatment of critically ill patients has not been explored. This study aims to understand better whether and how frequently cannabinoids have been administered to critically ill patients in recent years.

Cytosine methylation in GABA B1 receptor identifies alcohol-related changes for men in blood and brain tissues.

Aims: Alcohol use alters the reward signaling processes contributing to the development of addiction. We studied the effects of alcohol use disorder (AUD) on brain regions and blood of deceased women and men to examine sex-dependent differences in epigenetic changes associated with AUD. We investigated the effects of alcohol use on the gene promoter methylation of GABBR1 coding for GABAB receptor subunit 1 in blood and brain.

Chronic Voluntary Alcohol Consumption Alters Promoter Methylation and Expression of and .

Alcohol abuse accounts for 3.3 million deaths annually, rendering it a global health issue. Recently, fibroblast growth factor 2 (FGF-2) and its target, fibroblast growth factor receptor 1 (FGFR1), were discovered to positively regulate alcohol-drinking behaviors in mice.

Comparing DRD2 Promoter Methylation Between Blood and Brain in Alcohol Dependence.

Aims: The dopamine receptor D2 (DRD2) is substantially involved in several forms of addiction. In addition to genetic polymorphisms, epigenetic mechanisms have emerged as an important means of regulation. Previously, DRD2 hypo- and hyper-methylation have been observed in alcohol use disorder (AUD).

Dysregulated Methylation Patterns in Exon IV of the Brain-Derived Neurotrophic Factor (BDNF) Gene in Nicotine Dependence and Changes in BDNF Plasma Levels During Smoking Cessation.

Introduction: Several studies reported dysregulated protein levels of brain-derived neurotrophic factor (BDNF) in smokers and during cessation. However, the epigenetic regulation of the BDNF gene has not yet been investigated. We measured the plasma levels of BDNF and the epigenetic regulation of exon IV of the BDNF gene in smokers compared to healthy controls over a cessation period of 14 days.

Neurohumoral Profiles and Childhood Adversity of Patients with Multisomatoform Disorder and Pain as the Leading Bodily Symptom.

Objective: Patients suffering from chronic pain often present with multifactorial underlying conditions, sometimes without concrete pathological physical findings. Functional somatic syndromes (FSS) and somatoform disorders show a high prevalence of 8-20% and are often associated with adverse childhood experiences (ACE) and chronic stress. As many different FSS have overlapping symptoms, the concept of multisomatoform disorder (MSD) has been introduced as an encompassing concept.

Leptin promoter methylation in female patients with painful multisomatoform disorder and chronic widespread pain.

Background: Different functional somatic syndromes (FSS), fibromyalgia (FMS) and other unexplained painful conditions share many common clinical traits and are characterized by troubling and functionally disabling somatic symptoms. Chronic pain is most frequently reported and at the center of patients' level of disease burden. The construct of multisomatoform disorder (MSD) allows to subsume severely impaired patients suffering from FSS, FMS and other unexplained painful conditions to be examined for common underlying processes.

Sudden infant death syndrome revisited: serotonin transporter gene, polymorphisms and promoter methylation.

Background: Based on findings in the brain stems of SIDS victims, the serotonin transporter (5-HTT) gene has been discussed to be associated with SIDS.

Methods: In the largest study to date, we investigated the promoter length (5-HTTLPR) and intron 2 VNTR polymorphisms in 274 cases and 264 controls and the Ile425Val polymorphism in 65 cases and 64 controls. Moreover, the methylation of the internal promoter region was investigated in 35 cases and 14 controls.

Differences in the promoter methylation of atrial natriuretic peptide and vasopressin in alcohol use disorder. A longitudinal case-control-study during withdrawal therapy.

Background: Both atrial natriuretic peptide (ANP) and vasopressin (VP) influence alcohol intake and withdrawal as well as craving and are also regulated by epigenetic factors. Disturbances in expression and promoter methylation status have been described in patients suffering from alcohol use disorder and alcohol withdrawal therapy.

Objectives: In this study, we wanted to map the progression of cytosine-phosphatidyl-guanine (CpG) methylation of the respective gene promoter of ANP and VP immediately after starting alcohol withdrawal therapy when compared with healthy controls METHODS: We recruited 34 males suffering from alcohol addiction or harmful use alongside 43 healthy male controls.

Epigenetic Regulation of Neural Transmission after Cerebellar Fastigial Nucleus Lesions in Juvenile Rats.

Structural and functional abnormalities in the cerebellar midline region, including the fastigial nucleus, have been reported in neuropsychiatric disorders, also comprising the cerebellar cognitive affecting syndrome. In rats, early fastigial lesions reduce social interaction during development and lead to cognitive and emotional deficits in adults, accompanied by compromised neuronal network activity. Since epigenetic mechanisms are implicated in the etiology of neuropsychiatric disorders, we investigated whether fastigial nucleus lesions in juvenile rats would impact epigenetic regulation of neural transmission.

Trauma Severity in Early Childhood Correlates with Stress and Satiety Hormone Levels in a Pilot Cohort Receiving Diamorphine Maintenance Treatment.

Aims: Childhood trauma is of importance for the manifestation of substance-related disorders and maintenance of hypothalamic-pituitary-adrenal (HPA)-axis disorders. Since stress plays a crucial role in opioid compliance and craving, we investigated the immediate effects of diacetylmorphine application on the HPA axis. In particular, adrenocorticotropic hormone (ACTH) and cortisol secretion, as well as satiety regulating proopiomelanocortin peptides α-melanocyte-stimulating hormone (MSH) and β-endorphin (END) in a cohort of opioid-dependent patients in diamorphine maintenance treatment concerning the clinical severity of their childhood trauma.

Transient receptor potential ankyrin 1 promoter methylation and peripheral pain sensitivity in Crohn's disease.

Background: Crohn's disease is a chronic inflammatory disorder of the gastrointestinal tract associated with abdominal pain and diarrhea. Pain caused by Crohn's disease likely involves neurogenic inflammation which seems to involve the ion channel transient receptor potential ankyrin 1 (TRPA1). Since the promoter methylation of TRPA1 was shown to influence pain sensitivity, we asked if the expression of TRPA1 is dysregulated in patients suffering from Crohn's disease.

Alcohol consumption alters Gdnf promoter methylation and expression in rats.

Alcohol use disorder is one of the most disabling diseases worldwide. Glial-cell derived neurotrophic factor (Gdnf) shows promising results concerning the inhibition of alcohol consumption in rodent models. We investigated the epigenetic regulation of Gdnf following ethanol consumption and withdrawal in a rat model.

Fluoxetine induces glucose uptake and modifies glucose transporter palmitoylation in human peripheral blood mononuclear cells.

In line with the monoamine hypothesis of major depressive disorder (MDD), the clinical efficacy of the selective serotonin reuptake inhibitor fluoxetine has classically been ascribed to central serotonin enhancing properties. Current research described disturbances in brain energy metabolism in MDD. Additionally, fluoxetine showed beneficial effects in neuropsychiatric disorders associated with central energy imbalance.

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.

Childhood traumatization is associated with differences in TRPA1 promoter methylation in female patients with multisomatoform disorder with pain as the leading bodily symptom.

Background: The construct of multisomatoform disorder (MSD) is a common point of reference for patients in different somatic and psychosomatic specialties and therefore useful in studying large well-characterized cohorts of a prototype of a somatoform disorder and in parallel as a functional somatic syndrome (FSS). This disorder is characterized by distressing and functionally disabling somatic symptoms with chronic pain as the most frequent and clinically relevant complaint. Pain is perceived by nociceptive nerve fibers and transferred through the generation of action potentials by different receptor molecules known to determine pain sensitivity in pathophysiological processes.

Alcohol Withdrawal and Proopiomelanocortin Neuropeptides in an Animal Model of Alcohol Dependence.

Background: Alcohol is one of the leading threats to health worldwide. Craving for alcohol makes abstinence a difficult challenge by maintaining alcohol dependence. Many studies suppose the hypothalamic-pituitary-adrenal axis, especially the proopiomelanocortin (POMC)-derived neuropeptides, to mediate craving during withdrawal in alcohol dependence.

DNA Methylation of the Leptin Gene Promoter is Altered by Chronic Alcohol Exposure in an Animal Model for Alcohol Dependence.

Appetite-regulating peptides, such as leptin, are linked to craving and have been in the focus of alcohol dependence research for years. The objective of our study was to investigate the dynamics of leptin gene promoter methylation during alcohol withdrawal and specific treatment in a rodent (rat) model for alcohol dependence. DNA methylation was measured using direct bisulfite sequencing at 0 h, 24 h, and 6 days of alcohol withdrawal as well as after treatment with alpha-melanocyte-stimulating hormone (alpha-MSH), Beta-Endorphin, or saline.

Smoking-induced changes in leptin serum levels and c/EBPalpha-related methylation status of the leptin core promotor during smoking cessation.

Previous studies have provided evidence of an association between serum leptin levels and smoking as well as craving during smoking cessation. As promoter methylation also regulates leptin expression, we investigated the leptin gene promoter region of smokers before and after smoking cessation. Since leptin's core promoter region contains an essential c/EBPalpha transcription binding site, we narrowed our investigation to C-300 (-300 base pairs from the transcription start site) of that binding site.

Desacylghrelin but not acylghrelin is reduced during smoking cessation.

This study focused on the acetylation status of ghrelin examining acyl- and desacylghrelin and its effect on craving during 14 days of smoking abstinence. This is the first study demonstrating changes in desacylghrelin plasma levels in smokers compared to non-smokers while there was no difference of acylated ghrelin. Future studies should specifically refer to plasma ghrelin as either desacyl- or acylghrelin since both have different effects on tobacco-seeking behavior and the underlying physiology.

Epigenetic alterations of the POMC promoter in tobacco dependence.

Impaired regulation of the hypothalamic-pituitary-adrenal (HPA) axis is substantially involved in several psychiatric disorders. Smoking interferes with HPA axis by activating proopiomelanocortin (POMC) neurons and thus stimulating the expression of POMC. The POMC transcript is processed into several peptide hormones, such as adrenocorticotropic hormone (ACTH) and alpha-melanocyte-stimulating hormone (alpha-MSH), that play a role in stress response and weight control.

Epigenetic Effects of Intravenous Diacetylmorphine on the Methylation of POMC and NR3C1.

The administration of diacetylmorphine (DAM) reduces the activation of the hypothalamic-pituitary-adrenal (HPA) axis in opioid-maintained patients. However, the epigenetic effects of DAM on addiction-related genes have not been investigated yet. In a randomized controlled study, we examined the immediate effects of intravenous DAM versus placebo on the promoter methylation of the POMC (pro- opiomelanocortin) and NR3C1 (glucocorticoid receptor 1) genes.

P11 promoter methylation predicts the antidepressant effect of electroconvulsive therapy.

Although electroconvulsive therapy (ECT) is among the most effective treatment options for pharmacoresistant major depressive disorder (MDD), some patients still remain refractory to standard ECT practise. Thus, there is a need for markers reliably predicting ECT non/response. In our study, we have taken a novel translational approach for discovering potential biomarkers for the prediction of ECT response.