Suchergebnisse

<i>Aims:</i> Alcohol withdrawal seizures (AWS) are among the most important possible complications during the detoxification treatment of alcohol-dependent patients. Pharmacological therapy is often used during detoxification, but can cause dangerous side effects [Eur Addict Res 2010;16:179–184]. In separate studies several biological markers have been described as being associated with AWS risk. We investigated the role of homocysteine (HCT), carbohydrate-deficient transferrin (CDT) and prolactin (PRL) as biological markers for the risk of developing AWS. <i>Methods:</i> The present study included 189 alcohol-dependent patients of whom 51 had a history of AWS. We investigated the HCT, CDT and PRL levels of all patients and calculated sensitivity and specificity. Bayes' theorem was used to calculate positive (PPV) and negative (NPV) predictive values. <i>Results:</i> The highest combined sensitivity and specificity for %CDT was reached at a plasma cutoff value of 3.75%. The combination of HCT at a cutoff value of 23.9 µmol/l and %CDT at a cutoff value of 3.75% showed the best predictive values (sensitivity 47.1%, specificity 88.4%, PPV 0.504, NPV 0.870). <i>Conclusion:</i> A combined assessment of HCT and CDT levels can be a useful method to identify patients at a higher risk of AWS, which may lead to a more individualized therapy.

<b><i>Aims:</i></b> 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. <b><i>Methods:</i></b> We compared the serum levels of ACTH, cortisol, MSH, and END in 15 opioid-dependent patients. All participants received treatment with diamorphine and were observed at 5 timepoints before and after injection. We split the cohort into 2 subgroups concerning childhood trauma measured by the Childhood Trauma Questionnaire. <b><i>Results:</i></b> Splitting in 2 subgroups for mild (5) and severe trauma (10), we found that while both groups show a significant reduction of ACTH and cortisol levels over time, slopes display different progressions over time for cortisol (<i>F</i>[1.6] = 9.38, <i>p</i> = 0.02), while remaining identical for ACTH (<i>F</i>[1.6] = 1.69, <i>p</i> = 0.24). Also, levels of both MSH and END were significantly lower in severely traumatized patients. <b><i>Conclusions:</i></b> For the first time, we present a detailed representation of stress- and addiction-related proteins for the first 5 h after diamorphine application, demonstrating the interrelationship between stress hormones and childhood trauma as well as its potential effects on the progression of addictions such as opioid dependence.

Zusammenfassung. Ziel der Studie: Untersucht wurden die Einstellungen gegenüber Menschen mit Alkoholabhängigkeit und die Akzeptanz neurobiologischer sowie sozialer Krankheitsursachen. Methodik: Mit einem 75-Item Fragebogen wurden die Ansichten von 254 Teilnehmern erfragt und die Einstellungen gegenüber alkoholabhängigen Patienten von Betroffenen und gesunden Menschen verglichen. Die betroffenen alkoholabhängigen Patienten (n = 122) wurden während einer stationären qualifizierten Entzugsbehandlung befragt, nachdem der körperliche Entzug vorüber war. In den Vergleichsgruppen wurden medizinisches Personal (n = 70) sowie Studierende (n = 62) ohne medizinisches Hintergrundwissen befragt. Ergebnisse: Zwischen den Betroffenen und dem medizinischen Personal fanden wir keine Unterschiede bezüglich der Zuschreibung neurobiologischer Faktoren als Ursachen der Alkoholabhängigkeit. Studierende hielten neurobiologische Faktoren für weniger ursächlich für Alkoholabhängigkeit als Betroffenen und als medizinisches Personal. Bezüglich der sozialen Faktoren als Ursachen der Alkoholabhängigkeit ergaben sich keine signifikanten Unterschiede zwischen den drei Gruppen. Die Betroffenen bewerteten die Charaktereigenschaften alkoholabhängiger Patienten insgesamt positiver als das medizinische Personal und die Studierenden.Schlussfolgerung: Betroffene berichten positivere Einstellungen gegenüber Menschen die an einer Alkoholabhängigkeit leiden, als medizinisches Personal und als Studierende.

Disturbances of volume-regulating peptides like vasopressin (AVP) and atrial natriuretic peptide (ANP) have been described in early abstinent alcohol-dependent patients. In a longitudinal approach, we investigated whether changes in AVP and ANP serum levels correlated to cytosine-phosphatidyl-guanine (CpG) methylation of the respective gene promoters on days 1, 7 and 14 of alcohol withdrawal. We analyzed the blood samples of 99 patients suffering from alcohol dependence alongside age- and BMI-matched controls. Concerning AVP promoter methylation, we observed an interaction between time of measurement and CpG loci with CpG 2 showing a significant increase in methylation from day 1 to 14. Serum levels of AVP were significantly decreased in the patient group. Compared to healthy controls, promoter-related DNA methylation of the ANP promoter was significantly reduced on days 7 and 14. Moreover, we detected a significant interaction between CpG position and group. In both cases the difference was mainly observed at CpG 1. The present study shows significant changes in the methylation status of individual CpG sites of AVP and ANP. Observing respective alterations of AVP serum protein levels in alcohol-dependent patients during detoxification treatment, we consider methylation as a possible mode of regulation for these proteins during alcohol detoxification.

Preclinical study results suggest that neurotrophic peptides like nerve growth factor (NGF) and vascular endothelial growth factor A (VEGF-A) may be associated with symptoms of addictive behavior like withdrawal symptoms and rewarding effects. We investigated alterations in NGF and VEGF-A serum levels in opiate-dependent patients (25 male patients), who received diamorphine (DAM, heroin) treatment within a structured opiate maintenance program, and compared the results with the NGF and VEGF-A serum levels of healthy controls (23 male controls). NGF and VEGF-A serum levels were assessed before and after DAM administration twice a day (in the morning (16 h after last application – t1) and in the afternoon (7 h after last application – t3)) in order to detect a possible immediate or summative (in the afternoon) heroin effect on these two neuropeptides. Moreover, we investigated possible associations between the serum levels of these neurotrophic growth factors and psychometric dimensions of addictive behavior, e.g. craving, withdrawal, depression. Whereas there was no direct effect of DAM application on the serum levels of both neurotrophic growth factors neither in the morning nor in the afternoon, the NGF serum levels of the patient group were found to be significantly increased at all four time points of investigation compared with the healthy controls. In contrast, VEGF-A serum levels did not differ significantly in the patient and control groups. We found a significant positive association between the NGF serum levels and several items of the short opiate withdrawal scale as well as a negative association between self-reported mood (measured by visual analogue scale) and mood before heroin application (in the morning as in the afternoon). Moreover, we found a significant positive association between the NGF serum levels (t1 and t3) and the self-reported craving for methadone. In contrast, we found a negative association between the VEGF-A serum levels and avoidance, anxiety, suicide intentions of the SCL-90 as well as a positive association between the VEGF-A serum levels and the subscales of the heroin craving questionnaire measuring the rewarding effects of heroin. In conclusion, the results of this pilot study show that there might be an association between symptoms of opiate dependence and withdrawal and serum levels of VEGF-A and NGF.

<b><i>Aims:</i></b> 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. <b><i>Methods:</i></b> We compared methylation levels of opioid-dependent patients receiving treatment with diamorphine (<i>n</i> = 28) or levomethadone (<i>n</i> = 54) and similar levels in a healthy control group (<i>n</i> = 72). <b><i>Results:</i></b> 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]; <i>p</i> &#x3c; 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]; <i>p</i> = 0.03), cluster II ([EMM] [SE]: 0.133 [0.013] vs. 0.187 [0.014]; <i>p</i> &#x3c; 0.001) and cluster III ([EMM] [SE]: 0.190 [0.014] vs. 0.128 [0.016]; <i>p</i> &#x3c; 0.001). <b><i>Conclusions:</i></b> 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.

Acetaldehyde, the carcinogenic metabolite of ethanol known to provoke aversive symptoms of alcohol consumption, is predominantly eliminated by aldehyde dehydrogenase 2 (ALDH2). Reduced ALDH2 activity correlates with low alcohol tolerance and low risk for alcohol dependence. The ALDH2 promoter polymorphism rs886205 (A>G) is associated with decreased promoter activity, but a molecular mechanism and allele-dependent ALDH2 protein expression has not been described yet. On the basis of allele-dependent epigenetic effects, we analyzed the rs886205 genotype, methylation rates of cytosine-phosphatidyl-guanine (CpG)-sites within a regulatory promoter region and ALDH2 protein levels in 82 alcohol-dependent patients during a 2-week withdrawal and compared them to 34 matched controls. Patients without the G-allele of rs886205 showed higher methylation of the promoter region than controls and readily adapted epigenetically as well as on protein level during withdrawal, while patients with the G-allele displayed retarded methylation readjustment and no change in ALDH2 protein levels. Our data provide novel insights into an unknown genetic-epigenetic interaction, revealing impaired ALDH2 protein expression in patients with the G-allele of rs886205. Additionally, we checked for an association between rs886205 and protection against alcohol dependence and found a trend association between the G-allele and protection against alcohol dependence that needs replication in a larger Caucasian cohort.

Zusammenfassung. Hintergrund: Stigmatisierung schadet den Betroffenen und verstärkt Suchtprobleme. Sie ist ein Hindernis auf dem Weg zur Hilfe, führt zu schlechterer Behandlung und vergrößert die sozialen und gesundheitlichen Folgen einer Suchtkrankheit. Das gilt sowohl für die individuellen Folgen als auch für die gesellschaftlichen einschließlich der öffentlichen Gesundheitskosten. Zudem ist Stigmatisierung ein ethisches Problem, weil sie eine bestimmte Gruppe benachteiligt und die Menschenwürde der Betroffenen angreift. Ein stigmafreier Umgang mit Suchtkrankheiten ist möglich. Entstigmatisierung bedeutet, bessere Lösungen für Suchtprobleme zu finden und verfügbar zu machen. Nicht Abwertung, Ausgrenzung und Disziplinierung, sondern Wertschätzung und Befähigung (Empowerment) müssen im Zentrum von Prävention, Behandlung sowie dem alltäglichen Umgang mit Suchtkrankheiten stehen.