[Psychosocial Treatment of Addictive Disorders--An Overview of Psychotherapeutic Options and their Efficacy]. / Psychosoziale Behandlungen bei Suchterkrankungen--Suchtspezifische Psychotherapieformen und ihre Wirksamkeit.

Addictive disorders are chronic relapsing conditions marked by compulsive and often uncontrolled use of psychotropic substances or stimuli. In this review, we present and discuss the current specific psychosocial interventions for addictive disorders and their effectiveness. In particular cognitive behavioral therapy, motivational interviewing, relapse prevention, the community reinforcement approach, and contingency management were found to be effective. For these psychotherapeutic treatments, mostly moderate effect sizes have been found. Their effectiveness seems to be highest in cannabis dependence. Empirical evidence for dependence on "hard" drugs is largest for contingency management, while for alcohol dependence motivational interviewing and the community reinforcement approach show the largest effect sizes. Presumably, combinations of different approaches as well as online interventions will bring further progress in the psychosocial treatment of addictive disorders in the future.

[Alcohol and violence: a current review]. / Alkohol und Gewalt: Eine aktuelle Übersicht.

Violent behaviour under the influence of alcohol is a long-known phenomenon and causes great suffering in affected persons and enormous costs for society. While earlier studies considered alcohol-associated violence primarily to be due to alcohol's disinhibiting effects, recent scientific studies show a complex interaction of various bio-psycho-social factors. Including recent study results, the following review presents current data on the epidemiology of alcohol-associated violence, discusses possible contributing factors and causes, and possible resulting therapeutic implications. Based on these results, populations at risk such as binge drinkers, young adults and individuals with substance use disorders and comorbid psychiatric disorders can be identified, who often display a high burden of problems and therefore need a close network of medical, psychiatric and social services.

Tobacco smoking and depression--results from the WHO/ISBRA study.

AIMS: To elucidate the relationship between tobacco smoking and depression, and to estimate the impact of other substance dependencies. DESIGN: Cross-sectional. PARTICIPANTS: A total of 1,849 men and women were interviewed face-to-face using a validated structured questionnaire. According to their tobacco smoking behavior, participants were grouped into never smokers, ex-smokers and current smokers. MEASUREMENTS: Data were generated through the WHO/ISBRA study, an international multicenter study with a cross-sectional design. A standardized questionnaire was administered face-to-face by trained interviewers. Logistic regression analysis was used to predict depression. RESULTS: There was a significant difference across the 3 smoking groups in the number of subjects who had major depression (DSM-IV) during their lifetime. The highest rate of depressives was found in current smokers (23.7%), the lowest rate in never smokers (6.2%), while the rate of those who had quit smoking (14.6%) was between both. In a logistic regression analysis, alcohol dependence (both current and during lifetime) as well as cocaine dependence were significant predictors of depression. However, the association between smoking and depression still remained statistically significant. CONCLUSIONS: This study adds support to the evidence that smoking is linked to depression. It also elucidates the importance of taking into account alcohol and cocaine dependence since they have a significant impact on the relationship between smoking and depression.

Increased functional connectivity in the resting-state basal ganglia network after acute heroin substitution.

Reinforcement signals in the striatum are known to be crucial for mediating the subjective rewarding effects of acute drug intake. It is proposed that these effects may be more involved in early phases of drug addiction, whereas negative reinforcement effects may occur more in later stages of the illness. This study used resting-state functional magnetic resonance imaging to explore whether acute heroin substitution also induced positive reinforcement effects in striatal brain regions of protracted heroin-maintained patients. Using independent component analysis and a dual regression approach, we compared resting-state functional connectivity (rsFC) strengths within the basal ganglia/limbic network across a group of heroin-dependent patients receiving both an acute infusion of heroin and placebo and 20 healthy subjects who received placebo only. Subsequent correlation analyses were performed to test whether the rsFC strength under heroin exposure correlated with the subjective rewarding effect and with plasma concentrations of heroin and its main metabolites morphine. Relative to the placebo treatment in patients, heroin significantly increased rsFC of the left putamen within the basal ganglia/limbic network, the extent of which correlated positively with patients' feelings of rush and with the plasma level of morphine. Furthermore, healthy controls revealed increased rsFC of the posterior cingulate cortex/precuneus in this network relative to the placebo treatment in patients. Our results indicate that acute heroin substitution induces a subjective rewarding effect via increased striatal connectivity in heroin-dependent patients, suggesting that positive reinforcement effects in the striatum still occur after protracted maintenance therapy.

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.

Neuroendocrine support for a relationship between "novelty seeking" and dopaminergic function in alcohol-dependent men.

The personality traits "novelty seeking", "harm avoidance", and "reward dependence" were rated using Cloninger's Tridimensional Personality Questionnaire in 20 male inpatients, suffering from moderate to severe alcohol dependence (ICD-10, DSM-III-R). The same individuals' dopamine receptor sensitivity was determined by stimulating a neuroendocrine response with a dopamine receptor agonist (apomorphine). The amount of growth hormone released was measured and taken as a biological parameter for the sensitivity of D2 dopamine receptors located in the hypothalamus. Our data indicate that in abstinent alcohol-dependent men no statistically significant correlation exists between a person's apomorphine-induced growth hormone release and his "harm avoidance" or "reward dependence" score. On the other hand, a significant correlation (r = .47; p = .035) was found between growth hormone release and the person's "novelty seeking" score. This result supports Cloninger's hypothesis by giving neuroendocrine evidence that the personality dimension "novelty seeking" is related to dopaminergic activity in alcohol-dependent men.

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.

The Gly/Glu polymorphism of the neurotrophin 3 gene: allele frequencies in a Caucasian population and relevance for psychiatric disorders.

Using a modified method for the determination of the genotype of the neurotrophin 3 Gly/Glu polymorphism by PCR, we investigated allele frequencies in patients suffering from different psychiatric diseases as well as in healthy controls. There was a much lower frequency of the allele Glu among Caucasians (0.006) than previously reported for a Japanese population (0.203). No homozygotes and only three heterozygotes for the rare allele could be detected: the latter belonged to the patient group and suffered from endogenous depression (two patients) and hebephrenia (one patient). Due to its very low frequency it seems unlikely that the allele Glu plays a decisive role in the aetiopathogenesis of schizophrenic psychoses or other psychiatric diseases. However, it cannot be excluded that it represents a risk or vulnerability factor.

Alcohol withdrawal and dopamine receptor sensitivity after prolonged abstinence.

1. Forty-four male inpatients suffering from moderate to severe alcohol dependence (DSM-III-R and ICD-10) as well as 14 healthy controls entered this study. Individuals were classified according to the severity of their withdrawal symptoms during detoxification i.e. group 1) no withdrawal, group 2) autonomic hyperactivity, group 3) withdrawal delirium and group 4) controls. 2. During the 6th week of treatment, that is, when all patients were recovered, controlled abstinent, and several weeks away from the end of their withdrawal syndrome, dopamine receptor sensitivity was neuroendocrinologically assessed by stimulating human growth hormone (HGH) with apomorphine (APO). 3. In a repeated measures model ANOVA, the four groups differed significantly in their HGH release. However, when excluding the controls from the analysis and focusing on alcoholics only (group 1 - 3), the significant difference disappeared. Covariates such as age, weight, quantity of drinking and duration of dependence were not related to the dependent variable. 4. In conclusion, the first significant result (with controls) reflects a blunted HGH response in alcoholics. It confirms earlier reports. The second, non significant result with the alcohol dependents only, suggests that the severity of withdrawal is not reflected by the amount of HGH released. Therefore, in alcoholics, a reduced dopamine receptor function after six weeks of abstinence, as neuro-endocrinologically assessed with apomorphine, seems to be related to alcohol dependence rather than to the severity of alcohol withdrawal.

An evaluation of the history of a marijuana withdrawal syndrome in a large population.

Case reports and laboratory research indicate the existence of a cannabis withdrawal syndrome. However, the data tell us little about the prevalence and clinical characteristics of a marijuana withdrawal syndrome in people who have used the drug but who did not enter treatment for cannabis dependence. Face-to-face semi-structured interviews applying standard diagnostic criteria were used in the present study to gather data from 5611 men and women, recruited between 1991 and 1995 through the Collaborative Study of the Genetics of Alcoholism (COGA). Almost 41% of the sample had no history of marijuana use (Group 1), 28% had consumed this drug less than 21 times in any single year (Group 2), and 31% used it at least that frequently (Groups 3 and 4). Almost 16% of the more frequent marijuana users related a history of a marijuana withdrawal syndrome, and these Group 4 subjects had used the drug almost daily for an average of almost 70 months. The typical withdrawal symptoms included "nervous, tense, restlessness", "sleep disturbance" and "appetite change". While Group 4 subjects were more likely to have developed dependence on most types of drugs, even when alcohol and drug use patterns were statistically taken into account, marijuana use was still significantly related to a self-report of a history of marijuana withdrawal.

Alcohol dependence, family history, and D2 dopamine receptor function as neuroendocrinologically assessed with apomorphine.

Fifteen alcohol dependent men with an alcohol dependent first degree relative (i.e. family history positive or FHP), 15 well matched alcohol dependent men without a family history for alcohol dependence (i.e. family history negative or FHN), and 15 healthy controls (CONTR) participated in this study. The three groups were compared according to their postsynaptic D2 dopamine receptor function as assessed by growth hormone release after stimulation with the dopamine receptor agonist apomorphine. Statistical evaluation was done by planned comparisons within a one-way ANOVA. Alcohol dependent subjects significantly differed from CONTRs as long as family history was not taken into account (t(42) = 2.38; P = 0.022*). When differentiating according to family history, both FHPs and FHNs maintained a blunted growth hormone response. However, the difference between FHNs and CONTRs, though present, dropped out of statistical significance (t(42) = 1.65; P = 0.105); at the same time, the difference between FHPs and CONTRs became slightly stronger (t(42) = 2.47; p = 0.017*). In conclusion, our data give neuroendocrinological support to the assumption that a reduced D2 dopamine receptor function in alcohol dependent men is not only a state marker of residual heavy drinking but also a genetically determined trait marker.

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.

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.

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.

The relationship between Self-Rating of the Effects of alcohol and alcohol challenge results in ninety-eight young men.

OBJECTIVE: The level of intensity of response to a drug is likely to influence the future pattern of intake of the substance. This article evaluates a simple Self-Rating of the Effects (SRE) of alcohol form, and reports the relationship between a person's estimate of the amounts of alcohol usually required for four possible effects during three different time frames and his subjective feelings reported during an alcohol challenge. METHOD: SRE forms and results of a challenge with 0.9 ml/kg (0.72 g/kg) of ethanol were available for 18 to 29 year old drinking, but not alcohol dependent, men (N = 98). A subset of 40 subjects completed a second SRE form approximately 1 year later. RESULTS: The correlation between the two SRE administration was .82 (p < .0001), and the results on the SRE were internally consistent, with a higher number of drinks associated with more intense alcohol effects. Focusing on the subjective feelings reported at the 60-minute timepoint during the alcohol challenge, 11 of the 12 alcohol effect categories on the SRE correlated in the predicted direction, including eight that were statistically significant. Evaluating all seven timepoints during the drinking experiment, the average number of drinks on the SRE correlated significantly with the Subjective High Assessment Scale (SHAS) total score at all but the final timepoint. Sons of alcoholics and controls demonstrated similar levels of correlation between SRE and alcohol challenge results. Finally, the SRE correctly identified 79% of the individuals whose levels of response to alcohol fell into the lowest third of intensity during the alcohol challenge, and it correctly classified 60% to 67% of the alcohol challenge subjects who did not fall into that low response category. CONCLUSIONS: The SRE is a simple and reliable measure of a person's estimate of the number of drinks required to achieve a response. The form might be helpful in educating people about the intensity of their response to alcohol and might be useful as a point of discussion in curricula focusing on genetic aspects of alcoholism. When alcohol challenges are not possible in a research protocol, the SRE might help identify a less heterogeneous subgroup of individuals at high risk for alcoholism who have a common mechanism increasing their vulnerability.

[Comments on the definition of so-called "new addictions"]. / Bemerkungen zur Definition der sogenannten "Neuen Süchte".

To apply the term "addiction" to non-substantial addiction-like behavior is both problematic and useful. It is problematic because the uncritical application of the term has led to an inflation of addictions. If everything is called addiction the term is losing its predicative power and is getting meaningless. In the field of non-substantial addicted behavior we have been given the chance to study the phenomenon addiction in "pure" form without disturbing influences of any substance. To apply the term "addiction" to non-substantial addicted behavior is possible in principle. Von Gebsattel 1954 and Giese 1962 have already referred to this. However, it requires well-defined criterias. A strictly composition of the term would be recommendable.

Cognitive behavioral smoking cessation during alcohol detoxification treatment: a randomized, controlled trial.

BACKGROUND: Among alcohol-dependent subjects tobacco smoking is very common and causes a variety of health risks. Therefore, it is necessary to reach this high-risk population early with appropriate smoking interventions. METHODS: Smokers in alcohol detoxification treatment were offered to participate in a smoking cessation study. A total of 103 patients was enrolled and randomly assigned to either the experimental group (EG) receiving a cognitive behavioral smoking cessation treatment (CBT) or the control group (CG) receiving autogenic training. Smoking outcomes were measured by self-report and carbon monoxide levels, directly after intervention and 6 months later, where additionally alcohol outcomes were recorded. RESULTS: There were no differences in smoking quit rates directly after intervention. However, patients in the EG were significantly more likely to reduce their daily cigarette use compared to CG (p=.046). Sub-group analyses revealed that heavy smokers (FTND score ≥ 7) seemed to profit most in the EG regarding cigarette reduction. After 6 months, these positive effects had leveled out. No evidence was found that smoking cessation might jeopardize alcohol outcomes. CONCLUSIONS: Results suggest that alcohol-dependent smokers are interested in smoking interventions even during alcohol detoxification. CBT is promising in short-term smoking outcomes and in the approach of harm reduction, however, long-term effects are desirable. These findings underline the feasibility and the importance to provide smoking cessation interventions to patients in alcohol detoxification treatments.

Pilot study of the application of magnetic bead protein profiling to the study of biomarkers in addiction research.

OBJECTIVES: Proteomic technologies based on mass spectrometry are increasingly used as a valuable tool in clinical research allowing high-throughput protein and peptide profiling to be undertaken. Whilst previous research has focussed the application of this novel technology on the study of patients with disorders compared to comparable individuals from the healthy population, this current study seeks to determine the effect of successful treatment for alcoholism on the serum protein profile obtained. METHODS: Serum samples were collected from patients after initial treatment for alcohol abuse and also 6 months after treatment. The serum samples were prepared for analysis using reverse phase magnetic bead fractionation and the resulting peptides analysed by matrix assisted laser desorption ionisation time-of-flight (MALDI-ToF) mass spectrometry. RESULTS: Whilst the majority of the peptides detected by this approach exhibited constant levels between the two time points, three peptides were elevated at the 6-month time point compared to the initial sampling. CONCLUSIONS: Whilst disorders with very clear biological causes (such as cancer) exhibit significantly different peptide profiles, psychiatric disorders such as alcohol addiction which are multifactorial show less obvious changes. Despite this the two groups of samples could statistically be distinguished by certain peptides expression levels.

The impact of self-help group attendance on relapse rates after alcohol detoxification in a controlled study.

AIMS: Self-help groups such as Alcoholics Anonymous (AA) are widely recommended for aftercare of alcohol-dependent persons, even though scientific knowledge of its effectiveness is inconsistent. The aim of the present analysis was to elucidate whether persons attending AA groups regularly after detoxification have lower relapse rates within 1 year, compared to persons without self-help group attendance. METHODS: Data for the present analysis were derived from the placebo-group of a multi-centre study in Germany (Wiesbeck et al., 2001). Patients were free to choose either self-help group attendance (N = 50) or no support (N = 28). RESULTS: After 1-month of follow-up, there was a lower relapse rate in patients attending a self-help group as compared to the control group, a difference, however, that leveled off during the following months. Moreover, relapse rates did not differ significantly at any point of time between both groups. Levels of social functioning improved in both groups over 1 year. CONCLUSIONS: The present study was unable to show an advantage of self-help group attendance in reducing relapses compared to the control group.