[Family-focused treatment approaches for drug-addicted parents]. / Familienzentrierte Behandlungsansätze für drogenabhängige Eltern.

BACKGROUND: In Germany 1.5-2.75 million children live in families affected by substance use disorders. Substance abuse can impact on family interactions in many ways. If a dependent parental drug use continues over a longer period of time, this can have pronounced psychological and social consequences for the (co)affected children. Nevertheless, family-focused treatment approaches are not yet widely used in the context of addiction treatment. AIM: This review article aims to provide an overview of the prevalence of parenthood among dependent drug users in Germany, the impact of dependent drug use on families and family-focused treatment approaches. METHODS AND RESULTS: Recording parenthood is particularly difficult in the case of dependent drug users as they often do not openly discuss it with their therapists because of the fear of consequences from youth welfare services. In order to change this, a structured recording of parenthood by the treatment providers is required. This is the prerequisite for being able to offer family-focused treatment to those affected. In Germany, three evidence-based therapy programs are available for this purpose: SHIFT, SHIFT Plus and MAMADAM. Additionally, a number of programs developed in the Anglo-American region can also be used. In contrast, the evidence for web-based programs is much weaker. DISCUSSION: In order to establish family-focused treatment approaches for drug-using parents across the board, long-term, secure funding is required. The necessary framework conditions must be created at a political level.

Aberrant functional brain network organization is associated with relapse during 1-year follow-up in alcohol-dependent patients.

Alcohol dependence (AD) is a debilitating disease associated with high relapse rates even after long periods of abstinence. Thus, elucidating neurobiological substrates of relapse risk is fundamental for the development of novel targeted interventions that could promote long-lasting abstinence. In the present study, we analysed resting-state functional magnetic resonance imaging (rsfMRI) data from a sample of recently detoxified patients with AD (n = 93) who were followed up for 12 months after rsfMRI assessment. Specifically, we employed graph theoretic analyses to compare functional brain network topology and functional connectivity between future relapsers (REL, n = 59), future abstainers (ABS, n = 28) and age- and gender-matched controls (CON, n = 83). Our results suggest increased whole-brain network segregation, decreased global network integration and overall blunted connectivity strength in REL compared with CON. Conversely, we found evidence for a comparable network architecture in ABS relative to CON. At the nodal level, REL exhibited decreased integration and decoupling between multiple brain systems compared with CON, encompassing regions associated with higher-order executive functions, sensory and reward processing. Among patients with AD, increased coupling between nodes implicated in reward valuation and salience attribution constitutes a particular risk factor for future relapse. Importantly, aberrant network organization in REL was consistently associated with shorter abstinence duration during follow-up, portending to a putative neural signature of relapse risk in AD. Future research should further evaluate the potential diagnostic value of the identified changes in network topology and functional connectivity for relapse prediction at the individual subject level.

Automatic Approach Behaviors in Alcohol Dependence: Does a Cognitive Bias Modification Training Affect Pavlovian-to-Instrumental Transfer Effects?

INTRODUCTION: Positively conditioned Pavlovian cues tend to promote approach and negative cues promote withdrawal in a Pavlovian-to-instrumental transfer (PIT) paradigm, and the strength of this PIT effect was associated with the subsequent relapse risk in alcohol-dependent (AD) patients. When investigating the effect of alcohol-related background cues, instrumental approach behavior was inhibited in subsequent abstainers but not relapsers. An automatic approach bias towards alcohol can be modified using a cognitive bias modification (CBM) intervention, which has previously been shown to reduce the relapse risk in AD patients. Here we examined the effects of such CBM training on PIT effects and explored its effect on the relapse risk in detoxified AD patients. METHODS: N = 81 recently detoxified AD patients performed non-drug-related and drug-related PIT tasks before and after CBM versus placebo training. In addition, an alcohol approach/avoidance task (aAAT) was performed before and after the training to assess the alcohol approach bias. Patients were followed up for 6 months. RESULTS: A stronger alcohol approach bias as well as a stronger non-drug-related PIT effect predicted relapse status in AD patients. No significant difference regarding relapse status or the number of heavy drinking days was found when comparing the CBM training group versus the placebo group. Moreover, there was no significant modulation effect of CBM training on any PIT effect or the aAAT. CONCLUSION: A higher alcohol approach bias in the aAAT and a stronger non-drug-related PIT effect both predicted relapse in AD patients, while treatment outcome was not associated with the drug-related PIT effect. Unlike expected, CBM training did not significantly interact with the non-drug-related or the drug-related PIT effects or the alcohol approach bias.

Binge and high-intensity drinking-Associations with intravenous alcohol self-administration and underlying risk factors.

Some styles of alcohol consumption are riskier than others. How the level and rate of alcohol exposure contribute to the increased risk of alcohol use disorder is unclear, but likely depends on the alcohol concentration time course. We hypothesized that the brain is sensitive to the alcohol concentration rate of change and that people at greater risk would self-administer faster. We developed a novel intravenous alcohol self-administration paradigm to allow participants direct and reproducible control over how quickly their breath alcohol concentration changes. We used drinking intensity and the density of biological family history of alcohol dependence as proxies for risk. Thirty-five alcohol drinking participants aged 21-28 years provided analytical data from a single, intravenous alcohol self-administration session using our computer-assisted alcohol infusion system rate control paradigm. A shorter time to reach 80 mg/dl was associated with increasing multiples of the binge drinking definition (p = 0.004), which was in turn related to higher density of family history of alcoholism (FHD, p = 0.04). Rate-dependent changes in subjective response (intoxication and stimulation) were also associated with FHD (each p = 0.001). Subsequently, given the limited sample size and FHD range, associations between multiples of the binge drinking definition and FHD were replicated and extended in analyses of the Collaborative Study on the Genetics of Alcoholism database. The rate control paradigm models binge and high-intensity drinking in the laboratory and provides a novel way to examine the relationship between the pharmacokinetics and pharmacodynamics of alcohol and potentially the risk for the development of alcohol use disorders.

Effects of moderate alcohol levels on default mode network connectivity in heavy drinkers.

BACKGROUND: It is well established that even moderate levels of alcohol affect cognitive functions such as memory, self-related information processing, and response inhibition. Nevertheless, the neural mechanisms underlying these alcohol-induced changes are still unclear, especially on the network level. The default mode network (DMN) plays an important role in memory and self-initiated mental activities; hence, studying functional interactions of the DMN may provide new insights into the neural mechanisms underlying alcohol-related changes. METHODS: We investigated resting-state functional connectivity (rsFC) of the DMN in a cohort of 37 heavy drinkers at a breath alcohol concentration of 0.8 g/kg. Alcohol and saline were infused in a single-blind crossover design. RESULTS: Intranetwork connectivity analyses revealed that participants showed significantly decreased rsFC of the right hippocampus and right middle temporal gyrus during acute alcohol exposure. Moreover, follow-up analyses revealed that these rsFC decreases were more pronounced in participants who reported stronger craving for alcohol. Exploratory internetwork connectivity analyses of the DMN with other resting-state networks showed no significant alcohol-induced changes, but suffered from low statistical power. CONCLUSIONS: Our results indicate that acute alcohol exposure affects rsFC within the DMN. Functionally, this finding may be associated with impairments in memory encoding and self-referential processes commonly observed during alcohol intoxication. Future resting-state functional magnetic resonance imaging studies might therefore also investigate memory function and test whether DMN-related connectivity changes are associated with alcohol-induced impairments or craving.

Translating preclinical models of alcohol seeking and consumption into the human laboratory using intravenous alcohol self-administration paradigms.

Preclinical models of alcohol use disorder (AUD) have advanced theoretical, mechanistic, and pharmacological study of the human condition. "Liking" and "wanting" behaviors reflect core processes underlying several models of AUD. However, the development and application of translational models of these preclinical approaches are at an incipient stage. The goal of this study was to examine how intravenous free-access and progressive-ratio, operant-response human alcohol self-administration paradigms can be used as translational human model parallels of preclinical "liking" and "wanting." Participants were 40 adults (mean age = 23.7, SD = 2.0; 45% female) of European descent who reported 12.6 drinking days (SD = 5.2) out of the previous 30 (average = 4.1 drinks per drinking day [SD = 1.7]). Individuals diverged in their alcohol self-administration behavior, such that free-access and progressive-ratio paradigm outcomes were not significantly correlated (p = 0.44). Free-access alcohol seeking was related to enjoying alcohol (p < 0.001), but not craving (p = 0.48), whereas progressive-ratio seeking at similar levels of alcohol exposure was related to craving (p = 0.02), but not enjoying (p = 0.30). Family history of alcoholism, venturesomeness traits, and disinhibition traits were unrelated (ps > 0.70) to preferred level of breath alcohol concentration (BrAC) in the free-access session, a measure of liking alcohol. Family history of alcoholism, disinhibition traits, and recent drinking history were significantly related (ps < 0.05) to alcohol seeking in the progressive-ratio paradigm, a measure of wanting alcohol. We conclude that intravenous alcohol self-administration paradigms show promise in modeling behaviors that characterize and parallel alcohol "liking" and "wanting" in preclinical models. These paradigms provide a translational link between preclinical methods and clinical trials.

Impact of Long-Term Alcohol Consumption and Relapse on Genome-Wide DNA Methylation Changes in Alcohol-Dependent Subjects: A Longitudinal Study.

BACKGROUND: Genetic factors play an important role in the development and maintenance of alcohol use disorder (AUD). Significant and widespread differences in methylation levels of multiple regions within the genome have been reported between AUD patients and healthy controls in large epigenome-wide association studies (EWASs). Also, within patient populations, methylation changes over time (both during and after withdrawal) have been identified as sensitive indicators for disease activity. The detection of changes in methylation levels is a powerful tool to further explore and understand the biological correlates and underpinnings of AUD. Although there is strong and convincing evidence for differences in methylation of various sites between AUD patients and controls, only few studies assessed changes within patients over longer periods of time while taking into account alcohol consumption, relapse, and abstinence. So far, the longest period assessed as a within-subject design using EWASs was 4 weeks. METHODS: Here, we investigated changes in whole-genome methylation levels within a sample of 69 detoxified AUD patients over a period as long as 12 months for the first time, comparing patients that relapsed within the follow-up period to those that remained abstinent. RESULTS: Whole-genome methylation patterns of individual CpG sites over time did not differ between abstinent and relapsing patients. However, there was a negative association between global mean methylation at the 12-month follow-up and alcohol consumption within our sample. CONCLUSION: Although the present study represents the largest study of methylation levels in a sample of AUD patients with a follow-up period of 1 year and accounting for alcohol consumption and relapse to date, the sample size might still not be large enough to detect genome-wide significant effects. Therefore, large-scale, long-term studies with AUD subjects are needed to determine the utility of DNA methylation for the assessment and monitoring of persons with alcohol use disorders.

Dysfunctional approach behavior triggered by alcohol-unrelated Pavlovian cues predicts long-term relapse in alcohol dependence.

We demonstrated that alcohol-dependent patients who relapsed within 1 year after detoxification showed stronger PIT effects compared with abstainers and controls. Relapsers particularly failed to correctly perform in trials where an instrumental stimulus required inhibition while a Pavlovian background cue indicated a monetary gain. Under that condition, relapsers approached the instrumental stimulus, independent of the expected punishment. The failure of inhibiting an aversive stimulus in favor of approaching an appetitive context cue reflects dysfunctional altered learning mechanisms in relapsers.

Neural correlates of instrumental responding in the context of alcohol-related cues index disorder severity and relapse risk.

The influence of Pavlovian conditioned stimuli on ongoing behavior may contribute to explaining how alcohol cues stimulate drug seeking and intake. Using a Pavlovian-instrumental transfer task, we investigated the effects of alcohol-related cues on approach behavior (i.e., instrumental response behavior) and its neural correlates, and related both to the relapse after detoxification in alcohol-dependent patients. Thirty-one recently detoxified alcohol-dependent patients and 24 healthy controls underwent instrumental training, where approach or non-approach towards initially neutral stimuli was reinforced by monetary incentives. Approach behavior was tested during extinction with either alcohol-related or neutral stimuli (as Pavlovian cues) presented in the background during functional magnetic resonance imaging (fMRI). Patients were subsequently followed up for 6 months. We observed that alcohol-related background stimuli inhibited the approach behavior in detoxified alcohol-dependent patients (t = - 3.86, p < .001), but not in healthy controls (t = - 0.92, p = .36). This behavioral inhibition was associated with neural activation in the nucleus accumbens (NAcc) (t(30) = 2.06, p < .05). Interestingly, both the effects were only present in subsequent abstainers, but not relapsers and in those with mild but not severe dependence. Our data show that alcohol-related cues can acquire inhibitory behavioral features typical of aversive stimuli despite being accompanied by a stronger NAcc activation, suggesting salience attribution. The fact that these findings are restricted to abstinence and milder illness suggests that they may be potential resilience factors.Clinical trial: LeAD study, http://www.lead-studie.de , NCT01679145.

Effects of alcohol intoxication on self-reported drinking patterns, expectancies, motives and personality: a randomized controlled experimental study.

Alcohol intoxication may affect self-reports of alcohol use and related constructs, such as impulsivity and dependence symptoms. Improved knowledge about potential systematic reporting biases induced by alcohol, e.g. through disinhibition, may be relevant for the assessment of intoxicated individuals both in clinical routine and research. We therefore randomly assigned 54 socially drinking males aged 18 to 19 without lifetime diagnosis of DSM-IV alcohol dependence to one of two experimental arms: either placebo infusion at day 1 and alcohol infusion at day 2, or vice versa. The lab-based intravenous alcohol infusion produced a constant blood alcohol level of 0.08 percent. On each day, participants completed the Alcohol Use Disorders Identification Test, as well as other questionnaires on alcohol expectancies, drinking motives and substance use-related temperament traits. We found that alcohol significantly increased self-reported expectancies (tension reduction) and motives (conformity; η2  = .16-.23), but we observed no effect of sequence, i.e. alcohol first versus placebo first (Pcorr  ≥ .118). High baseline alcohol expectancies did not moderate alcohol effects (Pcorr  ≥ .462). We conclude that moderate alcohol intoxication might not generally affect the reliability of self-reported alcohol use, alcohol use problems and psychological concepts related to drinking behavior in young males without alcohol dependence. Future studies could examine larger, less selective and clinical samples for possible alcohol effects on self-report measures related to alcohol consumption.

Sex Differences in Motivation to Self-Administer Alcohol After 2 Weeks of Abstinence in Young-Adult Heavy Drinkers.

BACKGROUND: Studies in animal models document that forced abstinence from usual consumption of alcohol changes subsequent seeking and consumption, with increases or decreases depending on the species, duration of abstinence, number of deprivations, and sex. Human laboratory-based alcohol deprivation studies are rare. METHODS: We conducted a 2-session, within-participant, randomized-order comparison of intravenous, progressive ratio, alcohol self-administration during 2.5 hours of progressive work for alcohol and/or vehicle; once while the participants pursued their usual drinking habits and once after 2 weeks of closely monitored, voluntary outpatient abstinence from alcohol. The schedule of work for rewards and the incremental increases in breath alcohol concentration following completion of an alcohol work-set were identical across participants. Fifty young-adult (27 men), heavy-drinking participants completed both sessions. Our primary hypothesis was that motivation to work for alcohol after 2 weeks of abstinence would be greater in participants with a weekly binge pattern of drinking, compared to those who regularly drink heavily, and we intended to explore associations with biological family history of alcoholism and sex. RESULTS: We detected no change in work for alcohol associated with recent drinking history. However, females, on average, increased their work for alcohol upon resumption after 2 weeks of abstinence (mean ± SEM = +16.3 ± 9.6%), while males decreased that work (-24.8 ± 13.8%). The sex difference was substantial and significant (p < 0.03), with a medium effect size (Cohen's d = 0.63). CONCLUSIONS: We believe a more comprehensive study of mechanisms underlying the sex differences in the human postabstinence response is warranted.

Targeted intervention: Computational approaches to elucidate and predict relapse in alcoholism.

Alcohol use disorder (AUD) and addiction in general is characterized by failures of choice resulting in repeated drug intake despite severe negative consequences. Behavioral change is hard to accomplish and relapse after detoxification is common and can be promoted by consumption of small amounts of alcohol as well as exposure to alcohol-associated cues or stress. While those environmental factors contributing to relapse have long been identified, the underlying psychological and neurobiological mechanism on which those factors act are to date incompletely understood. Based on the reinforcing effects of drugs of abuse, animal experiments showed that drug, cue and stress exposure affect Pavlovian and instrumental learning processes, which can increase salience of drug cues and promote habitual drug intake. In humans, computational approaches can help to quantify changes in key learning mechanisms during the development and maintenance of alcohol dependence, e.g. by using sequential decision making in combination with computational modeling to elucidate individual differences in model-free versus more complex, model-based learning strategies and their neurobiological correlates such as prediction error signaling in fronto-striatal circuits. Computational models can also help to explain how alcohol-associated cues trigger relapse: mechanisms such as Pavlovian-to-Instrumental Transfer can quantify to which degree Pavlovian conditioned stimuli can facilitate approach behavior including alcohol seeking and intake. By using generative models of behavioral and neural data, computational approaches can help to quantify individual differences in psychophysiological mechanisms that underlie the development and maintenance of AUD and thus promote targeted intervention.

Impulsive Decision Making in Young Adult Social Drinkers and Detoxified Alcohol-Dependent Patients: A Cross-Sectional and Longitudinal Study.

BACKGROUND: Impulsive decision making relates to problematic substance use. Specifically, altered delay discounting (DD) has been suggested as a behavioral marker for addiction, while other relevant facets of choice impulsivity such as probability discounting (PD) or loss aversion are clearly understudied. METHODS: Two studies were performed collecting behavioral data on choice impulsivity with a value-based decision-making battery providing estimates of DD, PD for gains and losses, and loss aversion. Study (1): In a sample of 198 male 18-year-old social drinkers, we analyzed impulsive choice behavior and its association with alcohol consumption and self-report measures of substance use-related personality traits on a cross-sectional level. Additionally, the predictive value of baseline choice behavior for the trajectories of alcohol consumption over a 12-month follow-up period was evaluated. Study (2): Behavioral data on choice impulsivity were collected for 114 detoxified patients with alcohol use disorder (AUD) and 98 control participants. We analyzed group differences at baseline and assessed the predictive value of choice impulsivity for relapse to heavy alcohol use in patients during a follow-up period of 48 weeks. RESULTS: Study (1): Only DD was associated with baseline alcohol use, but no measure of choice impulsivity predicted the drinking trajectories over the following 12 months. Study (2): Compared to the control group, AUD patients showed higher DD, lower risk aversion regarding probabilistic gains, lower risk seeking regarding probabilistic losses, and lower loss aversion facing mixed prospects. Further, shallow discounting of probabilistic losses at baseline was predictive for relapse in patients. CONCLUSIONS: All 4 domains of impulsive decision making were considerably altered in AUD patients though mostly not related to alcohol use in young adult social drinkers. This suggests that these facets of impulsive behavior may develop as consequences of chronic alcohol consumption. Furthermore, discounting of probabilistic losses might prove valuable in identifying patients vulnerable for relapse.

Acute alcohol intoxication among adolescents-the role of the context of drinking.

This study aims (1) to describe the context of drinking among adolescents with acute alcohol intoxication (AAI) by gender, (2) to explore temporal changes in the context of drinking and (3) to analyse the association between the context of drinking and blood alcohol concentration (BAC). A retrospective chart review of 12- to 17-year-old inpatients with AAI (n = 1441) of the years 2000 to 2006 has been conducted in five participating hospitals in Germany. Gender differences in the context of drinking were tested with t test and chi2 test. Differences over time were analysed using logistic regressions. Multivariate linear regression was used to predict BAC. Girls and boys differed in admission time, drinking situation, drinking occasion and admission context. No temporal changes in drinking situation and in admission to hospital from public locations or places were found. Higher BAC coincided with male gender and age. Moreover, BAC was higher among patients admitted to hospital from public places and lower among patients who drank for coping. CONCLUSION: The results suggest gender differences in the context of drinking. The context of drinking needs to be considered in the development and implementation of target group-specific prevention and intervention measures. What is known: • The context of drinking, e.g. when, where, why and with whom is associated with episodic heavy drinking among adolescents. What is new: • Male and female inpatients with acute alcohol intoxication differ with regards to the context of drinking, i.e. in admission time, drinking situation, drinking occasion and admission context. • Being admitted to hospital from public places is associated with higher blood alcohol concentration.

Acute effect of intravenously applied alcohol in the human striatal and extrastriatal D2 /D3 dopamine system.

Investigations on the acute effects of alcohol in the human mesolimbic dopamine D2 /D3 receptor system have yielded conflicting results. With respect to the effects of alcohol on extrastriatal D2 /D3 dopamine receptors no investigations have been reported yet. Therefore we applied PET imaging using the postsynaptic dopamine D2 /D3 receptor ligand [18 F]fallypride addressing the question, whether intravenously applied alcohol stimulates the extrastriatal and striatal dopamine system. We measured subjective effects of alcohol and made correlation analyses with the striatal and extrastriatal D2 /D3 binding potential. Twenty-four healthy male µ-opioid receptor (OPRM1)118G allele carriers underwent a standardized intravenous and placebo alcohol administration. The subjective effects of alcohol were measured with a visual analogue scale. For the evaluation of the dopamine response we calculated the binding potential (BPND ) by using the simplified reference tissue model (SRTM). In addition, we calculated distribution volumes (target and reference regions) in 10 subjects for which metabolite corrected arterial samples were available. In the alcohol condition no significant dopamine response in terms of a reduction of BPND was observed in striatal and extrastriatal brain regions. We found a positive correlation for 'liking' alcohol and the BPND in extrastriatal brain regions (Inferior frontal cortex (IFC) (r = 0.533, p = 0.007), orbitofrontal cortex (OFC) (r = 0.416, p = 0.043) and prefrontal cortex (PFC) (r = 0.625, p = 0.001)). The acute alcohol effects on the D2 /D3 dopamine receptor binding potential of the striatal and extrastriatal system in our experiment were insignificant. A positive correlation of the subjective effect of 'liking' alcohol with cortical D2 /D3 receptors may hint at an addiction relevant trait.

[Increasing Consumption of Crystal Meth in Saxony and its Risks for Mother and Child - Experiences at a Level I Perinatal Center from a Pediatric Viewpoint]. / Steigender Konsum von Crystal Meth in Sachsen und dessen Risiken für Mutter und Kind ­ Erfahrungen an einem Perinatalzentrum Level I aus pädiatrischer Sicht.

Over the past several years, the number of first-time users of methamphetamine considerably increased within the Free State of Saxony. This number also, and especially, includes women of child-bearing age and young mothers. A supportive intervention aimed at reducing the effects of drug abuse should begin in a timely way - during pregnancy at latest, but better before it. To develop an optimal care protocol for both the mother and her child, more knowledge regarding the personal conditions of the women as well as the specific features of later child development after prenatal methamphetamine exposure (PME) is vital. In this study, the data of 129 women and their newborns with PME who were admitted to a Level-1 perinatal center between 2007 and 2015 were analyzed. At delivery, two-thirds of the women were aged 20-30 years. Only 48% attended their first preventive examination in pregnancy within the first 12 weeks. Their children subsequently presented with heterogeneous withdrawal symptoms, and pathological findings of the heart, urogenital and central nervous system. The present data aims to sensitize pediatric and obstetric health professionals to the need for timely and adequate care and support. A pathway model of detoxification treatment for mother and child - "The Dresden Crystal Path" - is presented. It combines public and voluntary youth welfare organizations, public health authorities, a public drugs advisory service as well as medical care facilities. Moreover, it describes the coordination of different medical subspecialties such as pediatrics, obstetrics/gynecology and psychiatry.

Don't Think, Just Feel the Music: Individuals with Strong Pavlovian-to-Instrumental Transfer Effects Rely Less on Model-based Reinforcement Learning.

Behavioral choice can be characterized along two axes. One axis distinguishes reflexive, model-free systems that slowly accumulate values through experience and a model-based system that uses knowledge to reason prospectively. The second axis distinguishes Pavlovian valuation of stimuli from instrumental valuation of actions or stimulus-action pairs. This results in four values and many possible interactions between them, with important consequences for accounts of individual variation. We here explored whether individual variation along one axis was related to individual variation along the other. Specifically, we asked whether individuals' balance between model-based and model-free learning was related to their tendency to show Pavlovian interferences with instrumental decisions. In two independent samples with a total of 243 participants, Pavlovian-instrumental transfer effects were negatively correlated with the strength of model-based reasoning in a two-step task. This suggests a potential common underlying substrate predisposing individuals to both have strong Pavlovian interference and be less model-based and provides a framework within which to interpret the observation of both effects in addiction.

Adolescent Women Induce Lower Blood Alcohol Levels Than Men in a Laboratory Alcohol Self-Administration Experiment.

BACKGROUND: Adolescence is a critical period for the development of alcohol use disorders; drinking habits are rather unstable and genetic influences, such as male sex and a positive family history of alcoholism (FH), are often masked by environmental factors such as peer pressure. METHODS: We investigated how sex and FH modulate alcohol use in a sample of 18- to 19-year-olds from the Dresden Longitudinal Study on Alcohol use in Young Adults. Adolescents reported their real-life drinking in a TimeLine Follow-Back interview. They subsequently completed a training and an experimental session of free-access intravenous alcohol self-administration (i.v. ASA) using the computer-assisted alcohol infusion system to control for environmental cues as well as for biological differences in alcohol pharmacokinetics. During i.v. ASA, we assessed subjective alcohol effects at 8 time points. RESULTS: Women reported significantly less real-life drinking than men and achieved significantly lower mean arterial blood alcohol concentrations (aBACs) in the laboratory. At the same time, women reported greater sedation relative to men and rated negative effects as high as did men. A positive FH was associated with lower real-life drinking in men but not in women. In the laboratory, FH was not linked to i.v. ASA. Greater real-life drinking was significantly positively associated with higher mean aBACs in the laboratory, and all i.v. ASA indices were highly correlated across the 2 sessions. CONCLUSIONS: We conclude that adolescent women chose lower aBACs because they experienced adverse alcohol effects, namely sedation and negative effects, at lower aBACs than men. A positive FH was not apparent as risk factor for drinking in our young sample. The i.v. ASA method demonstrated good external validity as well as test-retest reliability, the latter indicating that a separate training session is not required when employing the i.v. ASA paradigm.

Prediction of Long-Term Outcomes in Young Adults with a History of Adolescent Alcohol-Related Hospitalization.

AIMS: Empirical data concerning the long-term psychosocial development of adolescents admitted to inpatient treatment with alcohol intoxication (AIA) are lacking. The aim of this study was to identify the factors that, at the time of admission, predict future substance use, alcohol use disorders (AUD), mental health treatment, delinquency and life satisfaction. METHODS: We identified 1603 cases of AIA treated between 2000 and 2007 in one of five pediatric departments in Germany. These former patients were invited to participate in a telephone interview. Medical records were retrospectively analyzed extracting potential variables predicting long-term outcomes. RESULTS: Interviews were conducted with 277 individuals, 5-13 [mean 8.3 (SD 2.3)] years after treatment, with a response rate of 22.7%; of these, 44.8% were female. Mean age at the interview was 24.4 (SD 2.2) years. Logistic and linear regression models revealed that being male, using illicit substances and truancy or runaway behavior in adolescence predicted binge drinking, alcohol dependence, use of illicit substances and poor general life satisfaction in young adulthood, explaining between 13 and 24% of the variance for the different outcome variables. CONCLUSIONS: This naturalistic study confirms that known risk factors for the development of AUD also apply to AIA. This finding facilitates targeted prevention efforts for those cases of AIA who need more than the standard brief intervention for aftercare.

Pavlovian-to-instrumental transfer effects in the nucleus accumbens relate to relapse in alcohol dependence.

In detoxified alcohol-dependent patients, alcohol-related stimuli can promote relapse. However, to date, the mechanisms by which contextual stimuli promote relapse have not been elucidated in detail. One hypothesis is that such contextual stimuli directly stimulate the motivation to drink via associated brain regions like the ventral striatum and thus promote alcohol seeking, intake and relapse. Pavlovian-to-Instrumental-Transfer (PIT) may be one of those behavioral phenomena contributing to relapse, capturing how Pavlovian conditioned (contextual) cues determine instrumental behavior (e.g. alcohol seeking and intake). We used a PIT paradigm during functional magnetic resonance imaging to examine the effects of classically conditioned Pavlovian stimuli on instrumental choices in n = 31 detoxified patients diagnosed with alcohol dependence and n = 24 healthy controls matched for age and gender. Patients were followed up over a period of 3 months. We observed that (1) there was a significant behavioral PIT effect for all participants, which was significantly more pronounced in alcohol-dependent patients; (2) PIT was significantly associated with blood oxygen level-dependent (BOLD) signals in the nucleus accumbens (NAcc) in subsequent relapsers only; and (3) PIT-related NAcc activation was associated with, and predictive of, critical outcomes (amount of alcohol intake and relapse during a 3 months follow-up period) in alcohol-dependent patients. These observations show for the first time that PIT-related BOLD signals, as a measure of the influence of Pavlovian cues on instrumental behavior, predict alcohol intake and relapse in alcohol dependence.