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Biomedical subjects

G A Wiesbeck

Publications and source records attributed to G A Wiesbeck.

At least 19 recordsLinked to original sources
PubMed2005

[Psychosocial stress and alcohol consumption: interrelations, consequences and interventions].

BACKGROUND: Psychosocial stress can not only be considered as a result of chronic alcohol abuse, but also as a cause of high alcohol consumption and it maintains as a distress syndrome the subsequent course of the alcohol use disorder. METHODS: This review summarises empirical research results concerning the interrelations between psychosocial stress and alcohol consumption. The effects of psychosocial stress are regarded as an ideal-typical process leading to an increased alcohol intake and later to chronic alcohol abuse, often ending in alcohol dependence. The aim of the study is to demonstrate the relevance of stress and distress for diagnostics and therapy of alcohol- related disorders. RESULTS: At the starting point of high alcohol consumption psychological relief due to the stress-reducing effects of alcohol is often assumed. A vicious circle begins, perpetuating psychosocial distress and reinforcing the anxious or depressive symptoms related to emerging distress syndromes. Associated frequent comorbidities during the progression are other substance- related disorders, anxiety and affective disorders. Following alcohol dependence severe somatic and psychosocial consequences have to be anticipated. CONCLUSIONS: Psychosocial stress, distress and psychological effects can be understood as an important psychopathological developmental process of prolonged alcoholism. Symptoms of distress may be a first relevant evidence of high and hazardous alcohol consumption. Alcoholic patients should be motivated early to attend psychiatric and psychotherapeutic treatments to improve their chances for a positive development. Positive results can be achieved with stress management programs in alcohol dependent patients. These interventions appear to have comparable effects to other treatments.

Alcoholism↗
PubMed2003

Dopamine D2 (DAD2) and dopamine D3 (DAD3) receptor gene polymorphisms and treatment outcome in alcohol dependence.

The dopaminergic system is critically involved in reward mechanisms mediating the reinforcing effects of alcohol. The intention of this study was to investigate the genotypic frequencies of the -141C Ins/Del polymorphism of the DAD2 receptor gene as well as the Bal I polymorphism of the DAD3 receptor and their potential association with treatment outcome in alcoholism. Therefore, individuals suffering from primary alcohol dependence were clinically and genetically characterized and followed prospectively over a period of one year after inpatient treatment. No association was found between DAD2 or DAD3 receptor gene variants and treatment outcome as reflected by abstinence/relapse after one year. Taking into account potential stratification effects, such as family history, gender, age of onset, or severity of the disease an association with DAD2 or DAD3 gene variants could neither be found. In conclusion, we found no evidence that the DAD2 or DAD3 gene variants investigated have a major influence on treatment outcome in primary alcohol dependence.

Adult↗
PubMed2003

Gender-related differences in pharmacological relapse prevention with flupenthixol decanoate in detoxified alcoholics.

A study recently finished by our research group elucidated the effectiveness of flupenthixol decanoate (FLX) in maintaining abstinence in detoxified alcoholics. Flupenthixol decanoate is an established antipsychotic drug, which is well known for its mild antidepressant and anxiolytic activity as well as for its minimal sedation at low doses. It blocks dopamine binding at a number of receptor subtypes, primarily at D-1, D-2, D-3 and with less affinity at D4-receptors. It also affects serotonin binding at 5-HT2A and 5-HT2C receptors. In a double-blind placebo-controlled multicenter trial, 77 women and 204 men suffering from moderate or severe DSM-II-R alcohol dependence were randomly assigned to either 10 mg FLX or placebo both injected every second week over a period of 24 weeks (treatment phase) succeeded by a medication-free 24-weeks follow-up period. In the overall analysis the number of patients relapsed after 24 weeks of treatment (=main criterion of efficacy) was significantly higher in the FLX treated group (85.2%) than under placebo (65.5%). However, when differentiating this result according to sex the analysis revealed a gender-related discrepancy: while male patients had an almost 4-fold higher risk to relapse under FLX than under placebo (OR=3.95) this risk was barely elevated for female patients (OR=1.51). A significantly negative outcome due to FLX treatment was restricted to male alcoholics solely. In conclusion, gender-related differences to pharmacological relapse prevention with FLX have probably contributed to a better treatment outcome in women than in men.

Adult↗
PubMed2003

The candidate gene approach in alcoholism: are there gender-specific differences?

It is well established that genetic factors play a major role in the development of alcoholism in both sexes. Several twin studies demonstrated a nearly equally high magnitude of genetic influence for men and women. However, the genetic sources of vulnerability are supposed to only partially overlap in men and women. Therefore, we evaluated the gender-specific effects of two single nucleotide polymorphisms affecting dopaminergic neurotransmission (dopamine D2 receptor: -141C Ins/Del polymorphism; Dopamine D3 receptor: Bal I) in our large sample of primary alcoholics. Only a gender-specific analysis of subgroups with a putatively high genetic load, e.g., family-history-positive or presence of severe withdrawal complications, revealed significant differences in allele-/genotype-frequency. Our results demonstrate that a varying sex distribution in the samples investigated might contribute to the heterogeneous results reported in association studies for candidate genes in alcoholism and, therefore, should be taken into account in future studies.

Adult↗
PubMed2003

Gender and personality in alcoholism.

The topic gender and personality in alcoholism is discussed on the background of a research project on clinical aspects of alcoholism at the University of Würzburg, Germany. The data of this study are presented in the context of two questions: Which personality differences are there between women and men dependent on alcohol, and is there a connection between these personality differences and features of the alcohol dependence? Additionally, we take a look at gender-related differences in the development of alcoholism. In a first step, gender differences in the development and the course of alcoholism are investigated. The data revealed only weak differences between female and male alcoholics when important confounding variables like age and education are taken into consideration. Secondly, the female and male alcoholics are matched according to age and education and their personality structures are compared by using several well-established and standardized self-report questionnaires. No serious gender differences concerning the main characteristics of alcohol dependence could be discovered. However, some remarkable personality differences between female and male alcoholics are found: women scored significantly higher on Neuroticism and Harm-Avoidance while men reached significantly higher scores on Venturesomeness and Sensation-Seeking. In order to detect a possible connection between alcoholism and gender-related personality differences, both males and females are subdivided into two groups using the scores of Neuroticism, Harm-Avoidance, Venturesomeness and Sensation-Seeking, respectively. We have found no indication for a gender-specific relevance of personality differences between female and male alcoholics with regard to Harm-Avoidance, Venturesomeness or Sensation-Seeking. However, differences in Neuroticism have revealed a greater relevance in alcohol-dependent women than in men.

Adolescent↗
PubMed2001

Neuroendocrine responses to fenfluramine and its relationship to personality in alcoholism.

This study investigates the relationship between personality and serotonergic reactivity in alcohol dependence. Personality characteristics were assessed according to the Temperament and Character model of Cloninger, the five-factor model of McCrae and Costa, Zuckerman's Sensation Seeking as well as Eysenck's impulsiveness/venturesomeness. Placebo-controlled prolactin response to the serotonin (5-HT) reuptake inhibitor/releaser fenfluramine served as an indicator for the reactivity of serotonergic neurotransmission. Forty abstinent alcohol-dependent men were subdivided into high and low prolactin responders according to their level of neuroendocrine response. High responders were characterized by decreased harm avoidance while their extraversion and venturesomeness scores were increased in comparison to low responders. The data demonstrates that harm avoidance on the one hand and extraversion/venturesomeness on the other are inversely correlated to serotonergic neurotransmission. These results support a specific relationship between personality traits and the serotonergic system.

Adult↗
PubMed2001

Pharmacological relapse prevention in alcohol dependence: from animal models to clinical trials.

This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The chairs were Jobst August-Ludwig Boening and Otto Michel Lesch. The presentations were (1) Pharmacological validation of a new animal model of alcoholism, by Rainer Spanagel; (2) Persisting loss of control as main criterion for alcohol addiction in rats and mice, by Jochen Wolffgramm; (3) Role of NMDA receptor subunits associated with protein kinase C in the prevention of alcohol dependence, by Minoru Narita; (4) Long-term follow up of continued naltrexone treatment, by David Sinclair; (5) Pharmacological treatment trials with dopaminergic and serotonergic substances: Myths or facts? by Gerhard A. Wiesbeck; and (6) Methodology and behavioral therapy of the U.S. acamprosate study, by Barbara J. Mason.

Acamprosate↗
PubMed2000

Craving for alcohol and dopamine receptor sensitivity in alcohol-dependent men and control subjects.

Detoxified alcohol-dependent men and control subjects were repetitively exposed by sight and smell to either a neutral cue (tea) or an alcohol-related cue (their favourite alcoholic beverage) to provoke a maximum craving response. Additionally, their dopamine receptor sensitivity was evaluated by measuring growth hormone (HGH) response to stimulation with the dopamine receptor agonist apomorphine (APO). It was hypothesized that the subjects' desire to drink (craving) is related to their dopaminergic activity. In both groups, craving increased in the presence of the alcohol stimulus with significantly higher craving scores in alcoholics than in controls. However, in none of the groups and at no cue exposure did the craving response correlate with the individuals' dopaminergic activity as reflected by HGH release. Therefore, this study cannot add support to the hypothesis that craving for alcohol is associated with dopamine receptor sensitivity in abstinent alcoholics or healthy control subjects.

Adult↗
PubMed2000

Genome polymorphism and alcoholism.

Different gene variants have been identified as risk or protective factors in alcoholism. The genes coding for dopamine receptors, serotonin transporters, and dehydrogenases represent susceptibility loci for addictive behaviour. However, alcoholism represents a complex psychiatric symptomatology which is caused by multiple factors, both genetic and environmental. Furthermore, there are probably different subtypes of alcoholism each with a distinct pathophysiology, and thus a different genetic background. Genetic research can help to identify such subtypes, which may require different therapeutic approaches. However, gene polymorphisms are not only responsible for a predisposition to alcoholism, but also for personality traits which influence the likelihood of developing addictive behaviour. Moreover, genetic polymorphisms are probably involved in the way an individual responds to treatment. Also, the severity of secondary diseases resulting from chronic alcohol uptake may depend on the genetic makeup of an individual. New treatment strategies focusing on genes contributing towards drug and alcohol dependence (such as gene therapy) are already under examination in animal models. However, further research is required before these developments will considerably change today's clinical handling of alcoholism.

Alcoholism↗
PubMed2000

Event-related potentials and cue-reactivity in alcoholism.

BACKGROUND: Relapse is a major problem in the treatment of addictive behaviors. Conditioning models of alcohol addiction suggest that stimuli associated with previous drug use (cues) may initiate relapse in a definite group of alcoholics. Event-related potentials (ERPs) might be useful to reveal the brain functional substrates of cue-reactivity. METHODS: In a preliminary investigation, 11 alcohol-dependent patients who did not take part in the electrophysiological study completed a structured interview to rate 80 words as to the degree of relatedness to alcohol. Based on these results, cue-reactivity for 15 alcohol-related and 15 unrelated word cues, each repeated eight times, was investigated in 19 alcohol-dependent men (44.2 +/- 8.5 years) and 19 healthy control men (42.5 +/- 12.5 years). RESULTS: A cue-reactivity that consisted of significantly higher amplitudes in the ERPs after alcohol-related words compared with unrelated words was found in alcohol-dependent patients, but not in controls, at the electrode location Pz [F(1,36) = 5.2,p < 0.05]. CONCLUSIONS: Consistent with the hypothesis, only alcohol-dependent patients were characterized by signs of increased cerebral activity associated with alcohol-related compared with unrelated cues. Therefore, the results support the concept of cue-reactivity in alcoholism based on a neurobiological measurement. Future investigations will show whether this cue-reactivity can be applied to assess the risk of relapse in individual alcohol-dependent patients.

Adult↗
PubMed1999

[Temperament- and character traits as well as trait patterns in alcoholic men and controls].

This study is on the personality of alcoholics, an empirical investigation based on Cloninger's biopsychological temperament- and character-traits. His Temperament and Character Inventory (TCI) was applied to 94 detoxified men suffering from primary alcohol dependence as well as to controls matched for sex and sociodemographic data. The following questions were the matter of interest: (1) Do alcoholics and controls differ in their personality as reflected by the TCI and (2) are there indicators based on personality with potential relevance for differential therapies? A multiple univariate statistical comparison yielded significant differences between alcoholics and controls on only 2 subscales (Sentimentality, Resourcefulness). A multivariate analysis of the TCI temperament traits using two-sample configural frequency analysis revealed no statistically significant difference between the two groups. Temperament patterns associated with Cloninger's Type-I/Type-II alcoholics could not be demonstrated. Analyzing the temperament and character traits of the alcohol dependent subjects with a log-linear model revealed two bivariate temperament-/character classifications on the scales "Harm Avoidance" and "Self-Directedness" as well as "Reward Dependence" and "Self Transcendence"-both making it possible to define subgroups which may be relevant for different therapeutical approaches. Taken together, the results of this study suggest that it may be useful to closer investigate the personality of alcoholics even if it is not principally different from that of control subjects.

Adult↗
PubMed1999

Dopamine D3 receptor gene polymorphism and alcohol dependence: relation to personality rating.

Hereditary dopaminergic mechanisms have been implicated in the aetiology of alcoholism. For this study, the distribution of a dopamine D3 receptor gene polymorphism (Ball) has been investigated in patients suffering from alcohol dependence, and compared with non-dependent controls. The allele A1 occurred significantly more frequently among patients compared to controls. Patients with the genotype A1/A2 showed significantly higher novelty seeking (NS) scores in the tridimensional personality questionnaire (TPQ) than patients with the genotype A1/A1. The distribution of patients with high and low NS scores in heterozygotes (A1/A2) did not follow a random distribution. There were significantly more individuals with higher NS scores, and fewer individuals with lower NS scores than expected. The results of this study support the hypothesis of a genetically determined involvement of the dopaminergic system in alcohol dependence. This is probably related to the modulation of personality traits. The observed effects are relatively small, but statistically significant. Thus, the genetics of the dopaminergic neurotransmitter system alone cannot explain the aetiopathogenesis of alcoholism.

Adult↗
PubMed1999

Ritanserin in relapse prevention in abstinent alcoholics: results from a placebo-controlled double-blind international multicenter trial. Ritanserin in Alcoholism Work Group.

Ritanserin, a long-acting specific 5-HT2 receptor antagonist, revealed promising effects on alcohol intake behavior in both animal and preliminary human studies. To test its effectiveness in alcohol dependence this phase III clinical trial was initiated. In a placebo-controlled, randomized, double-blind international multicenter study 493 patients with moderate or severe alcohol dependence (DSM-III-R) were treated with three doses of ritanserin 2.5 mg/day (n = 122), 5 mg/day (n = 123), 10 mg/day (n = 126), or placebo (n = 122) over a period of 6 months. Ritanserin was well tolerated. The most frequent adverse experiences were headache and insomnia. A small increase in weight in the ritanserin-treated patients was observed. There were no significant differences between any dose of ritanserin and placebo in the relapse-rate, the time to relapse, craving for alcohol, or quantity and frequency of drinking after relapse. So far, neither ritanserin nor any other serotonergic medication has shown its specific effectiveness in relapse prevention in alcohol dependence.

Adult↗
PubMed1998

Growth hormone response to placebo, apomorphine and growth hormone releasing hormone in abstinent alcoholics and control subjects.

Abstinent alcoholics and control subjects were challenged with placebo (saline), growth hormone releasing hormone (GHRH) and apomorphine (APO). While both groups did not differ in their growth hormone response (HGH) to placebo and GHRH, the alcoholics revealed a significant lower HGH response to dopamine receptor stimulation with APO. These findings provide no evidence that in abstinent alcoholics HGH blunting after dopamine receptor stimulation could be related to an alteration at the pituitary level but they give neuroendocrinological support to the hypothesis of a lower dopamine receptor sensitivity in abstinent alcoholics.

Adult↗
PubMed1997

Time course of manganese superoxide dismutase concentrations in serum of alcohol-dependent patients during abstinence.

Mean manganese superoxide dismutase (Mn-SOD) concentrations in the serum of patients suffering from alcohol dependence is almost twice as high as in serum of non-dependent controls. In order to investigate the time course of this parameter during abstinence, we determined it at different time points. Patients had mean Mn-SOD serum concentrations (+/-S.D.) of 150.4 +/- 76.3, 121.1 +/- 40.7, 94.6 +/- 37.8 micrograms/ml at 1, 10 and 40 days after abstinence compared to 76.3 +/- 16.9 micrograms/ml as mean Mn-SOD value in the control group. Although the Mn-SOD concentration tended to normalise during abstinence, the differences between index and control group remained significant up to the last measurement at day 40.

Adult↗
PubMed1997

Oxidative-stress associated parameters (lactoferrin, superoxide dismutases) in serum of patients with Alzheimer's disease.

In this case/control study, serum levels of oxidative stress related parameters such as Fe-binding lactoferrin (LTF), Mn- and Zn,Cu-superoxide dismutase (SOD) were determined by enzyme linked immunoassays in patients suffering from the Alzheimer's dementia as well as in non-demented controls. The Mn-SOD concentration was significantly (P<0.05, U-test) reduced in patients suffering from Alzheimer's disease if compared to non-demented controls. The other parameters investigated did not differ significantly between both groups. Our findings give evidence for the hypothesis of a disturbed free radical metabolism in Alzheimer's disease. The specificity of these results remains to be clarified. Further studies are needed to elucidate the relevance of oxidative stress in the etiopathogenesis of the Alzheimer's disease.

Aged↗