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Background Alcohol use disorder (AUD) leads to a significant individual and societal burden. To achieve higher therapy success rates, therapeutic interventions still need to be improved. Most current neuroscientific conceptualizations of AUD focus on the imbalance between an enhanced automatic reaction to alcohol cues and impaired inhibition. Complementary to traditional relapse prevention strategies, novel computerized training interventions aim to directly alter these processes. This study tests a computerized alcohol-specific inhibition training in a large clinical sample and investigates its effects on behavioral, experimental and neurophysiological outcomes. It also analyzes whether variations in inhibition difficulty and/or endogenous cortisol levels during training impact these effects. Methods This is a double-blind, randomized controlled trial (RCT) with 246 inpatients with AUD participating. After baseline assessment, participants are randomly assigned to one of three computerized Go-NoGo-based inhibition training interventions (two alcohol-specific versions with different Go/NoGo ratios, or neutral control training) and one of two intervention times (morning/afternoon), resulting in six study arms. All patients perform six training sessions within 2 weeks. Endogenous cortisol is measured in 80 patients before and after the first training session. Inhibitory control and implicit associations towards alcohol are assessed pre and post training, at which point electroencephalography (EEG) is additionally measured in 60 patients. Patients’ alcohol consumption and relevant psychological constructs (e.g., craving, self-efficacy, treatment motivation) are measured at discharge and at 3-, 6- and 12-month follow-ups. Fifty healthy participants are assessed (20 with EEG) at one time point as a healthy control group. Discussion This study investigates the effects of a computerized, alcohol-specific inhibition training for the first time in patients with AUD. Results should give insight into the effectiveness of this potential add-on to standard AUD treatment, including proximal and distal measures and effects on behavioral, experimental and neurophysiological measures. Information about working mechanisms and potential optimizations of this training are gathered through variations regarding difficulty of inhibition training and training time. This study may thus contribute to a deepened understanding of AUD and the improvement of its evidence-based treatment. Trial registration ClinicalTrials.gov, ID: NCT02968537 . Registered on 18 November 2016. Electronic supplementary material The online version of this article (10.1186/s13063-019-3505-2) contains supplementary material, which is available to authorized users.

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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 [γcontrol = 74.30; γimproved = 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 (γstandard = 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.

Childhood trauma (CT) is frequent in patients with alcohol use disorder (AUD) and may impact on adult drinking behaviour and treatment outcome. This study aimed to investigate the structural correlates of CT in AUD, focusing on the amygdala, which plays a crucial role in the neurobiology of trauma. We hypothesized reduced amygdala volume and reduced structural connectivity as quantified by fractional anisotropy (FA) and by number of streamlines in those AUD patients with a history of moderate to severe CT (AUD‐CT). T1‐weighted MP2RAGE and diffusion‐weighted imaging (DWI) 3‐Tesla MRI‐scans were acquired in 41 recently abstinent patients with AUD. We compared bilateral amygdala volume and structural connectivity (FA and number of streamlines) of pathways emanating from the amygdala between AUD‐CT (n = 20) and AUD without CT (AUD‐NT, n = 21) using a mixed model multivariate analysis of variance (MANCOVA) controlling for age and gender. AUD‐CT displayed reduced FA and reduced number of streamlines of amygdalar tracts. There were no differences regarding amygdala volume. The severity of physical abuse, a subscale of the childhood trauma questionnaire, was negatively correlated with FA and with number of streamlines. AUD‐CT and AUD‐NT differ regarding structural connectivity of pathways projecting to and from the amygdala, but not regarding amygdala volume. Those alterations of structural connectivity in AUD‐CT may represent a distinguishable neurobiological subtype of AUD, which might be associated with the complex clinical picture and poorer outcome that patients with CT and AUD often present.