Maria Stein

Background: Alcohol use disorder (AUD) and depression are highly prevalent and tied to significant psychological, physiological, social and economic consequences. Their co‐occurrence presents a complex clinical challenge, as the impact of antidepressant medication on AUD outcomes remains equivocal. In this multicenter, longitudinal study we investigated the relationship between antidepressant medication and changes in depression symptoms and alcohol use in AUD patients.Methods: We analyzed data from 153 detoxified AUD patients who attended a 12‐week residential treatment program between 2015 and 2019. Within a mediation analysis, adopting a bootstrapping approach and a quasi‐Bayesian framework, we estimated the total, direct, and mediated effects of antidepressants on the percentage of days abstinent to assess the role of changes in depression symptoms as a mediating factor.Results: The mediation analysis revealed a dual impact pathway model with a negative direct effect of antidepressants on abstinence (p = 0.004) and a positive indirect effect, mediated through the reduction of depression symptoms (p = 0.002).Conclusions: The findings of the mediation analysis show that patients treated with antidepressants and whose depression symptoms do not improve over time show more relapses, while patients treated with antidepressants who achieve a reduction in depression symptoms show fewer relapses over time. Thus, to optimize treatment outcome, depression symptoms should be vigilantly monitored when antidepressants are prescribed during AUD treatment.

Aims: For the first time, to our knowledge, in a clinical sample with alcohol use disorder (AUD), this study compared the effects of two versions of alcohol‐specific inhibition training (Alc‐IT) on drinking outcomes and on experimental parameters assessing two possible working mechanisms: stimulus devaluation and inhibitory enhancement.Design: Multi‐centre, double‐blind, three‐arm clinical RCT with 3‐, 6‐ and 12‐month follow‐up comparing standard Alc‐IT, improved Alc‐IT and an active control condition.Setting: Three specialized AUD treatment centres in Switzerland.Participants: A total of 242 detoxified, recently abstinent patients with severe AUD (18–60 years; 29.8% female).Intervention and Comparator: Both interventions [standard Alc‐IT (n = 84) and improved Alc‐IT (n = 79)] and the comparator [unspecific inhibition training (n = 79)] consisted of six sessions of a modified inhibitory task (Go/NoGo task) with alcohol‐related and neutral stimuli. Both versions of Alc‐IT required response inhibition in alcohol‐related trials but differed in Go/NoGo ratios (standard: 50/50; improved: 75/25), with improved Alc‐IT posing higher inhibitory demands. The control condition, an unspecific inhibition training, featured alcohol‐related pictures in Go as well as NoGo trials.Measurements: The primary outcome, percentage of days abstinent, was assessed at 3‐month follow‐up with a time‐line follow‐back interview.Findings: The group receiving improved Alc‐IT showed a significantly higher percentage of days abstinent at 3‐month follow‐up compared with the control group [γ_control = 74.30; γ_improved = 85.78; β = 11.48, 95% confidence interval (CI) = 2.57, 20.40, P = 0.012, adjusted r² = 0.062], while for standard Alc‐IT no effect significantly different from zero was detected (γ_standard = 70.95; β = −3.35, 95% CI = −12.20, 5.50, P = 0.457, adjusted r² = −0.04).Conclusions: Alcohol‐specific inhibition training with high inhibitory demands increased days abstinent at 3‐month follow‐up in patients with severe alcohol use disorder. Such an improved, inhibitory‐demanding, alcohol‐specific inhibition training outperformed the standard version of alcohol‐specific inhibition training, suggesting an inhibitory working mechanism.

Aims: Substance use disorders (SUD) are associated with cognitive deficits that are not always addressed in current treatments, and this hampers recovery. Cognitive training and remediation interventions are well suited to fill the gap for managing cognitive deficits in SUD. We aimed to reach consensus on recommendations for developing and applying these interventions.Design, Setting and Participants: We used a Delphi approach with two sequential phases: survey development and iterative surveying of experts. This was an on‐line study. During survey development, we engaged a group of 15 experts from a working group of the International Society of Addiction Medicine (Steering Committee). During the surveying process, we engaged a larger pool of experts (n = 54) identified via recommendations from the Steering Committee and a systematic review.Measurements: Survey with 67 items covering four key areas of intervention development: targets, intervention approaches, active ingredients and modes of delivery.Findings: Across two iterative rounds (98% retention rate), the experts reached a consensus on 50 items including: (i) implicit biases, positive affect, arousal, executive functions and social processing as key targets of interventions; (ii) cognitive bias modification, contingency management, emotion regulation training and cognitive remediation as preferred approaches; (iii) practice, feedback, difficulty‐titration, bias modification, goal‐setting, strategy learning and meta‐awareness as active ingredients; and (iv) both addiction treatment work‐force and specialized neuropsychologists facilitating delivery, together with novel digital‐based delivery modalities.Conclusions: Expert recommendations on cognitive training and remediation for substance use disorders highlight the relevance of targeting implicit biases, reward, emotion regulation and higher‐order cognitive skills via well‐validated intervention approaches qualified with mechanistic techniques and flexible delivery options.

Introduction: In individuals with alcohol use disorder (AUD), the brain areas underlying cue-induced reactions (e.g., cingulum, striatum, thalamus) and altered activation of these regions have been identified by functional neuroimaging. Neuronal responses to a complex alcohol-related context are yet to investigate. To better understand contextual effects as well as the interplay of cue-induced neural reactions and context exposure, the present study implemented an imagination procedure during functional magnetic resonance imaging (fMRI). Methods: Thirteen patients with AUD and 13 healthy controls completed two rounds of a cue-reactivity paradigm inside an MRI scanner. Two individualized imagination tasks were conducted before each of the two cue reactivity tasks. A 2 (group) × 2 (imagination) × 2 (picture-type) analysis of variance (ANOVA) was performed. Results: The ANOVA revealed a main effect for imagination with higher activation in bilateral thalamus and right caudate nucleus and an interaction effect between imagination and group in right thalamus and left caudate nucleus, due to the patient group reacting stronger during alcohol-related imagination. These structures are involved in relaying sensory information and habit learning. No main or interaction effects of picture type were observed. Conclusions: These results support the view that context effects alter the neural responses in thalamus and nucleus caudatus in patients with AUD, and that imagination tasks are suited to incorporate contextual influences in neurophysiological research designs. Future research needs to investigate whether the failure to observe a picture-type effect was due to limited statistical power and omission to individualize picture set, or whether an imagination procedure interferes with the evocation of picture-type effects.

Alcohol use disorder (AUD) is characterized by enhanced cue-reactivity and the opposing control processes being insufficient. The ability to inhibit reactions to alcohol-related cues, alcohol-specific inhibition, is thus crucial to AUD; and trainings strengthening this ability might increase treatment outcome. The present study investigated whether neurophysiological correlates of alcohol-specific inhibition (I) vary with craving, (II) predict drinking outcome in AUD and (III) are modulated by alcohol-specific inhibition training. A total of 45 recently abstinent patients with AUD and 25 controls participated in this study. All participants underwent functional magnetic resonance imaging (fMRI) during a Go-NoGo task with alcohol-related as well as neutral conditions. Patients with AUD additionally participated in a double-blind RCT, where they were randomized to either an alcohol-specific inhibition training or an active control condition (non-specific inhibition training). After the training, patients participated in a second fMRI measurement where the Go-NoGo task was repeated. Percentage of days abstinent was assessed as drinking outcome 3 months after discharge from residential treatment. Whole brain analyses indicated that in the right inferior frontal gyrus (rIFG), activation related to alcohol-specific inhibition varied with craving and predicted drinking outcome at 3-months follow-up. This neurophysiological correlate of alcohol-specific inhibition was however not modulated by the training version. Our results suggest that enhanced rIFG activation during alcohol-specific (compared to neutral) inhibition (I) is needed to inhibit responses when craving is high and (II) fosters sustained abstinence in patients with AUD. As alcohol-specific rIFG activation was not affected by the training, future research might investigate whether potential training effects on neurophysiology are better detectable with other methodological approaches.

Alcohol use disorder (AUD) is characterized by enhanced cue-reactivity and the opposing control processes being insufficient. The ability to inhibit reactions to alcohol-related cues, alcohol-specific inhibition, is thus crucial to AUD; and trainings strengthening this ability might increase treatment outcome. The present study investigated whether neurophysiological correlates of alcohol-specific inhibition (I) vary with craving, (II) predict drinking outcome in AUD and (III) are modulated by alcohol-specific inhibition training. A total of 45 recently abstinent patients with AUD and 25 controls participated in this study. All participants underwent functional magnetic resonance imaging (fMRI) during a Go-NoGo task with alcohol-related as well as neutral conditions. Patients with AUD additionally participated in a double-blind RCT, where they were randomized to either an alcohol-specific inhibition training or an active control condition (non-specific inhibition training). After the training, patients participated in a second fMRI measurement where the Go-NoGo task was repeated. Percentage of days abstinent was assessed as drinking outcome 3 months after discharge from residential treatment. Whole brain analyses indicated that in the right inferior frontal gyrus (rIFG), activation related to alcohol-specific inhibition varied with craving and predicted drinking outcome at 3-months follow-up. This neurophysiological correlate of alcohol-specific inhibition was however not modulated by the training version. Our results suggest that enhanced rIFG activation during alcohol-specific (compared to neutral) inhibition (I) is needed to inhibit responses when craving is high and (II) fosters sustained abstinence in patients with AUD. As alcoholspecific rIFG activation was not affected by the training, future research might investigate whether potential training effects on neurophysiology are better detectable with other methodological approaches.

This study aimed to investigate structural and functional alterations of the reward system and the neurobiology of craving in alcohol use disorder (AUD). We hypothesized reduced volume of the nucleus accumbens (NAcc), reduced structural connectivity of the segment of the supero-lateral medial forebrain bundle connecting the orbitofrontal cortex (OFC) with the NAcc (OFC-NAcc), and reduced resting-state OFC-NAcc functional connectivity (FC). Furthermore, we hypothesized that craving is related to an increase of OFC-NAcc FC. Thirty-nine recently abstinent patients with AUD and 18 healthy controls (HC) underwent structural (T1w-MP2RAGE, diffusion-weighted imaging (DWI)) and functional (resting-state fMRI) MRI-scans. Gray matter volume of the NAcc, white matter microstructure (fractional anisotropy (FA)) and macrostructure (tract length) of the OFC-NAcc connection and OFC-NAcc FC were compared between AUD and HC using a mixed model MANCOVA controlling for age and gender. Craving was assessed using the thoughts subscale of the obsessive-compulsive drinking scale (OCDS) scale and was correlated with OFC-NAcc FC. There was a significant main effect of group. Results were driven by a volume reduction of bilateral NAcc, reduced FA in the left hemisphere, and reduced tract length of bilateral OFC-NAcc connections in AUD patients. OFC-NAcc FC did not differ between groups. Craving was associated with increased bilateral OFC-NAcc FC. In conclusion, reduced volume of the NAcc and reduced FA and tract length of the OFC-NAcc network suggest structural alterations of the reward network in AUD. Increased OFC-NAcc FC is associated with craving in AUD, and may contribute to situational alcohol-seeking behavior in AUD.