Abstract Hallucinogenic new psychoactive substances (HNPS) mimic traditional hallucinogens and comprise different classes such as phenethylamines (e.g., 2C-B, NBOMe), tryptamines (e.g., DiPT), and lysergamides (e.g., 1-P-LSD). Like for classic hallucinogens (e.g., LSD or psilocybin), the most common acute adverse events are psychological conditions such as anxiety or paranoia. These symptoms are mostly self-limited and can be managed with supportive care. Benzodiazepines or neuroleptics can be used in severe cases. However, strong dopamine antagonists should be avoided due to their potential to exacerbate symptoms. However, due to the novelty of these substances and limited available data, the overall risks are difficult to assess. The variable potency and interactions with neurotransmitter systems that differ from those of classical hallucinogens can be problematic. While classic hallucinogens have a very low physical toxicity, there are several HNPS such as the NBOMe family that have been linked to fatalities and severe adverse effects, including serotonin syndrome, hyperthermia, cardiovascular events, and seizures. Long-term risks comprise psychotic symptoms and hallucinogen persisting perception disorder, but also dependence or organ damage in some cases. Raising awareness, promoting harm-reduction, and enhancing specialized care are essential steps in addressing the health risks of HNPS.

Background Repetitive transcranial magnetic resonance imaging is an effective treatment for depression. Accelerated TMS-protocols (aTMS) are applied several times per day and hold promise to rapidly decrease depressive symptoms. This study used high-resolution 7-Tesla MRI to anatomically precisely investigate aTMS-induced alterations of resting state functional connectivity (rs-FC) of the subgenual anterior cingulate cortex (sgACC). We hypothesized that aTMS reduces hyperactivation of the sgACC by decreasing rs-FC with key cortical regions. Furthermore, we explore associations between sgACC related rs-FC alterations, depression severity and mindfulness, which is often impaired in depression. Methods Twenty-four patients with current depression underwent 7-Tesla MRI-scans before and after a two-week aTMS treatment series (target: left dorsolateral prefrontal cortex, total number of pulses: 24,000). Fifteen healthy controls were also scanned twice for comparison, without receiving aTMS. Group × time interactions of changes in sgACC seed-based rs-FC were calculated. In addition, we examined baseline group differences of sgACC rs-FC. Correlations between longitudinal changes in sgACC rs-FC, depression severity, and mindfulness, were calculated. Results aTMS reduced rs-FC between the sgACC and the precuneus (core part of the default mode network; DMN), normalizing elevated baseline rs‑FC in depressed patients. No significant association was observed with changes in overall depression severity. However, decreases in sgACC–posterior DMN connectivity were significantly associated with improvements in mindfulness. Conclusions Treatment response in depression is associated with a normalization of rs‑FC alterations between the sgACC and the DMN. Observed changes might reflect processes related to improvements in mindfulness.

BACKGROUND:Neuroimaging studies in humans and translational animal models consistently demonstrate ECT-induced hippocampal volume increases. However, evidence linking hippocampal volume changes to clinical improvement in depression has been inconsistent. This systematic review with meta-analysis extends previous work to investigate whether hippocampal volume changes following the completion of an ECT-index series are associated with the clinical course of depression. METHODS:We conducted a systematic review and meta-analysis following PRISMA guidelines. Studies were eligible if they assessed hippocampal volume and included at least three imaging timepoints, with two performed after completion of the ECT-index series (t1 = pre-ECT, t2 = post-ECT, t3 = follow-up). Standardized mean change (SMC) was calculated for hippocampal volume and depressive symptom severity across timepoints. Pooled estimates were derived using random-effects models with restricted maximum likelihood (REML) estimation to account for between-study heterogeneity. Meta-regression analyses were performed to evaluate associations between volumetric changes and trajectories of depressive symptoms post-ECT. RESULTS:Fifteen studies (N = 447 patients) were included in the systematic review, with six studies (N = 151 patients) contributing complete volumetric data for meta-analysis. Hippocampal volumes increased significantly from t1 to t2 and largely returned to baseline at t3. Depression severity decreased substantially from t1 to t2 and remained stable at follow-up. Meta-regression analyses indicated no significant associations between changes of hippocampal volume and depressive symptoms from post-ECT to follow-up. Sensitivity analyses confirmed robustness of the findings. CONCLUSIONS:Hippocampal volume increases following ECT are transient and not associated with the clinical course of depression.

Repetitive transcranial magnetic stimulation (rTMS) is an efficient non-pharmacological therapy for patients with depression, including those with treatment resistant depression (TRD). Accelerated treatment TMS-protocols (aTMS) are applied several times a day and hold the promise for rapid and efficient treatment responses superior to conventional rTMS. A better understanding of the neurobiological underpinnings of aTMS-related neuroplasticity is crucial to advance the field. To this aim, we conducted a systematic review of studies investigating neuroplasticity of aTMS-treatment. Two investigators screened the established research literature databases for publications following the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines and using Patient/Population, Intervention, Comparison and Outcome (PICO) acronyms. Among the selected 22 studies assessing 958 participants the following imaging methods were applied: functional MRI (fMRI) (n = 15), structural MRI (n = 1), diffusion tensor imaging (DTI) (n = 1), arterial spin labelling (ASL) (n = 2), 18F-fluorodeoxyglucose positron emission tomography (18-FDG PET) (n = 1), and multimodal imaging (n = 2). The majority of reported aTMS-induced changes are confined to the anterior cingulate cortex (ACC), more specifically the subgenual ACC (sgACC). Associations between aTMS-induced neuroplasticity and clinical response were not consistent; however, the most frequently reported findings pertained to the sgACC. Future studies, investigating larger samples are required to consolidate the assumption that aTMS-induced plasticity of the sgACC may be associated with treatment response.

Emotion processing is a key domain in alcohol use disorder (AUD). Given the neuronal basis of emotion regulation and the neurophysiological deviations observed in AUD patients the present exploratory study investigates EEG Microstate (MS) correlates of emotional processing in patients with AUD and healthy controls (HC). Emotions, moods and emotion regulation competencies were assessed in 29 patients with AUD and 22 HC using self-report. Additionally, a 64-channel resting-state electroencephalography (EEG) was recorded for each individual and a microstate analysis yielding 7 classes (A-G) was performed. The effects of the factors group (patients with AUD vs. HC), emotion/emotion regulation (from self-report scales) and MS class (A-G) on the MS feature contribution were analyzed using linear models. Three-way interactions were observed for “awareness of feelings” (Bonferroni-corrected; F(6, 329) = 3.75, p = .001) and “shame” (F(6, 322) = 2.42, p = .026). Level of awareness of feelings correlated positively with MS C in HC, while an inverse correlation was found for MS D. No such association between awareness of feelings and MS C and D was observed in patients with AUD who rather displayed significantly higher overall MS C values than HC (tRatio(343) = -3.13, p = .002). The present study provides initial evidence that neuronal activity, as reflected in MSs, differs in relation to emotion processing between patients with AUD and healthy individuals. The results indicate that MS C and D might be neurophysiological markers for awareness of feelings in HC, while such an association is blunted in patients with AUD.

ObjectivesRescue workers face frequent occupational trauma, increasing their risk for posttraumatic stress symptoms (PTSS), depression, and suicidal ideation. However, pathways linking trauma to suicidality remain poorly understood. This study investigated these mechanisms by testing a serial mediation model.MethodsFrom a larger survey of Swiss rescue workers, participants reporting suicidal ideation (n = 44) were matched by age, sex, and profession with a control group without suicidal ideation (n = 44). Symptomatology was assessed using validated questionnaires such as the Posttraumatic Stress Scale-10 (PTSS-10) for posttraumatic stress and the Brief Symptom Inventory (BSI) for depressive symptoms. Structural Equation Modeling (SEM) was employed to test a serial two-mediator model: Trauma Exposure - PTSS - Depressive Symptoms - Suicidal Ideation.ResultsParticipants with suicidal ideation had significantly higher levels of trauma, PTSS, and depressive symptoms. SEM confirmed an excellent model fit (χ² = 1.925, CFI = 1.000, RMSEA <.001) and a full mediation effect: trauma exposure was associated with PTSS, which in turn related to depressive symptoms, which were subsequently linked to suicidal ideation. The specific serial indirect pathway was significant (B = 0.143, p = .011), while the direct path from trauma to suicidal ideation was non-significant. The model explained 69.4% of the variance in suicidal ideation.ConclusionThe findings suggest a developmental pathway in which trauma exposure is associated with suicidal ideation through the sequential roles of PTSS and depressive symptoms. Consequently, suicide prevention for rescue workers should prioritize the management of post-traumatic and depressive symptoms to potentially disrupt this symptomatic progression.

Zusammenfassung: Hintergrund: In der Schweiz kann Psilocybin im Rahmen von Ausnahmebewilligungen therapeutisch genutzt werden. Programm: Die Klinik Südhang entwickelte basierend auf Evidenz und Ethik ein standardisiertes Programm für Psilocybin-assistierte Gruppenpsychotherapie bei Abhängigkeitserkrankungen. Das quartalsweise durchgeführte Programm umfasst Diagnostik, mehrere Einzel- und Gruppensitzungen zur Vorbereitung, eine Psilocybin-Gruppensitzung sowie integrative Nachbesprechungen. Eine umfassende Qualitätssicherung, strenge Auswahlkriterien, spezifisch geschultes Personal und eine umfassende Vorbereitung erhöhen die Sicherheit. Das Gruppensetting fördert Ressourcen wie Zugehörigkeit, Akzeptanz und Mitgefühl und ermöglicht problemaktualisierende sowie klärende Erfahrungen. Erfahrungen: Bisher wurden in zwölf Zyklen 89 Behandlungen mit 36 Patient_innen ohne schwerwiegende Komplikationen durchgeführt. Schlussfolgerungen: Die Methode zeigt Potenzial für den Einsatz bei therapierefraktären Abhängigkeitserkrankungen, erfordert jedoch hohe therapeutische Kompetenz und institutionelle Ressourcen.

Anhedonia is a core feature of depression. It contains a consummatory and a motivational aspect. Whilst much neuroimaging research in patients with depression focused on the consummatory aspect of anhedonia, less is known about its motivational aspect. This study aimed to explore the neurobiology of networks related to motivational anhedonia. Thirty-eight patients with major depressive disorder (MDD) and 19 healthy controls underwent diffusion-weighted and resting state functional magnetic resonance imaging (rs-fMRI). For assessment of motivational anhedonia, we summed the values of the CORE non-interactiveness score, and the items 1 (hopelessness) and 7 (work and activities) of the Hamilton Depression Rating Scale. Whole-brain voxel-wise statistical analysis of fractional anisotropy (FA) data was performed using Tract-Based Spatial Statistics (TBSS). Additionally, we performed a whole-brain comparison of integrated local correlation of rs-fMRI signal (LCOR), to investigate regional functional differences between patients and healthy controls. Whole brain correlations between motivational anhedonia and measures of structural and functional connectivity (FA, and LCOR) were calculated. TBSS-analyses revealed reduced FA in the left superior longitudinal fasciculus (SLF) in patients with MDD. LCOR was reduced in patients with depression in an adjacent cluster localized in bilateral precunei. Within patients, there was a positive correlation between motivational anhedonia and LCOR in the precunei and a negative correlation in bilateral sensorimotor areas. FA-values did not show significant correlations. These findings suggest that motivational anhedonia in depression is linked to alterations of functional connectivity within bilateral precunei. Observed white matter microstructural alterations in the SLF do not show such an association.

Background: In Switzerland, psilocybin can be used therapeutically under special authorizations. Program: Based on evidence and ethical principles, Klinik S & uuml;dhang has developed a standardized program for psilocybin-assisted group psychotherapy targeting substance use disorders. The quarterly program includes diagnostic assessment, several individual and group preparation sessions, a psilocybin-assisted group session, and integrative follow-up meetings. Comprehensive quality assurance, strict selection criteria, specially trained staff, and thorough preparation ensure safety. The group setting fosters resources such as belonging, acceptance, and compassion, and enables the activation and resolution of core problems. Experiences: To date, twelve treatment cycles with a total of 89 sessions involving 36 patients have been completed without serious complications. Conclusions: The method shows promise for treatment-resistant substance use disorders but requires high therapeutic expertise and institutional resources.

Resting-state functional connectivity is limited in assessing the temporal dynamics of brain networks and, due to an insufficient signal-to-noise ratio, in detecting subtle changes at 3T MRI. Nonetheless, measures of complexity, which capitalize on temporal dynamics, have revealed alterations for some affective disorders at this field strength. Anxiety disorders have received only scant attention in this regard, despite indications of altered functional brain architecture in spider-fearful participants (SP). To address this gap, we probed resting-state complexity using 7T MRI, comparing 28 adults with SP with 45 healthy controls (HC). We computed multiscale entropy (MSE) on ten scales (1 - 0.1 Hz) for brain regions of the fear and anxiety networks in HC and SP. The MSE scales interacted with group (HC, SP) and brain area, revealing MSE increments in limbic regions in SP (versus HC). Whilst most MSE changes related to SP ranged between 1 and 0.33 Hz, the MSE of the bed nucleus of the stria terminalis (BNST), a nucleus involved in anxiety and the hormonal system, exhibited increases on all scales bar two for SP (i.e., for 0.5 - 0.125, and 0.1 Hz). MSE was also positively associated with SP severity (but not trait anxiety) in the BNST. Altogether, 7T fMRI detected elevated MSE in SP, indicating excessive intra-regional processing in brain regions key to fear and anxiety. The most pronounced effects were found in the BNST, corroborating its central role in the anxiety circuit.

INTRODUCTION:Depression is one of the most common mental disorders. The effectiveness of pharmacological and psychotherapeutic treatments is well documented. Remission rates are around 67 % for pharmacological antidepressant initial and secondary treatment of a depressive episode in unipolar disorders. However, patients with a depressive episode who do not respond to at least two successive attempts at pharmacological antidepressant treatment have significantly lower remission rates. Particularly in this subgroup with difficult-to-treat depression, brain stimulation procedures and treatment with novel substances represent innovative and effective treatment options that complement pharmacotherapy and psychotherapy. The aim of this paper is to provide an overview and outlook on the following treatment procedures: repetitive transcranial magnetic stimulation (rTMS), electroconvulsive therapy (ECT), ketamine/esketamine, transcranial direct current stimulation (tDCS), deep brain stimulation (DBS), and psychedelic-assisted psychotherapy (PAT). An outlook on selected current developments with the aim of a procedure-specific, individualized indication will be given.

Alcohol use disorder (AUD) represents a significant challenge in mental health. Severe AUD is characterized by uncontrolled alcohol consumption and is associated with dysregulation in brain circuits responsible for reward, motivation, decision-making, affect, and stress response. Mindfulness is known to positively influence those dysregulations and may enhance abstinence-related self-efficacy (confidence in resisting alcohol consumption), which is one of the best predictors for abstinence following inpatient treatment. Large-scale networks underlie mindfulness, including the default mode and salience network. This study aims to investigate the role of the cingulum bundle (CB) in patients with AUD, which bridges these two networks in relation to mindfulness and abstinence-related self-efficacy. We conducted a study with 39 recently abstinent inpatients with AUD and 18 healthy controls. Mindfulness and self-efficacy were assessed using standardized and validated self-report questionnaires. Structural and resting state functional magnetic resonance imaging (MRI) data were acquired to examine structural and functional connectivity of the cingulate cortex. Our findings showed reduced structural and functional connectivity of the CB in AUD patients with a highly positive association between these metrics. Overall, mindfulness correlated strongly with abstinence-related self-efficacy. We found no association of trait mindfulness and structural and functional findings of the cingulate cortex. However, exploratory analyses suggest a positive association between CB number of streamlines and mindfulness factors 'acceptance' and 'decentring', and abstinence-related self-efficacy. This is the first study indicating that patients with AUD have structural and functional impairments of the CB. These alterations could be associated with reduced mindfulness and self-efficacy.

BackgroundAlcohol 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.MethodsWe 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.ResultsThe 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).ConclusionsThe 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. Alcohol use disorder (AUD) and depression symptoms often co-occur and present a complex clinical challenge, as the impact of antidepressant medication on AUD outcomes remains ambiguous. In a multicenter, longitudinal study we investigated the relationship between antidepressant medication, changes in depression symptoms, and alcohol use. The mediation analysis revealed a negative direct effect of antidepressants on abstinence and a positive indirect effect, mediated through the alleviation of depression symptoms, highlighting the importance of monitoring of depression symptoms during AUD treatment.image

Sleep disturbances are common in depression, but their neurobiological correlates are poorly understood. Recent evidence suggests links between insula dysfunction and sleep dysregulation. This study aimed to explore the association of sleep quality and structural and functional characteristics of the insula in major depressive disorder (MDD). We included 47 patients with MDD and 15 healthy controls (HC) matched for age and sex. Sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI). Patients were classified into two subgroups with poor sleep (PAT-PS, PSQI > 8) and normal sleep (PAT-NS, PSQI ≤ 8), respectively. MRI-scans were acquired using structural and functional resting-state sequences. We analysed cortical thickness of bilateral insulae and connectivity strength of the insula to the whole brain using intrinsic connectivity. Group differences were assessed with a mixed-model MANCOVA controlling for age and sex. Patients had higher PSQI-scores than HC. PAT-PS (n = 21) and PAT-NS (n = 26) did not differ regarding age, sex and depression severity. Insular cortical thickness was reduced in PAT-PS compared to both HC and PAT-NS. Additionally, PAT-PS had lower insular intrinsic connectivity than HC. In contrast, there were no significant group differences in insular intrinsic connectivity between PAT-NS and HC. Across all subjects, PSQI-total was negatively associated with insular cortical thickness and insular intrinsic connectivity. Insular intrinsic connectivity within patients was negatively associated with depression severity. PSQI-total and depression severity did not correlate significantly. In conclusion, our results demonstrate that sleep disturbances in MDD patients are associated with structural and functional impairments of the insula.

BACKGROUND:Numerous studies show that electroconvulsive therapy (ECT) induces hippocampal neuroplasticity, but findings are inconsistent regarding its clinical relevance. This study aims to investigate ECT-induced plasticity of anterior and posterior hippocampi using mathematical complexity measures in neuroimaging, namely Higuchi's fractal dimension (HFD) for fMRI time series and the fractal dimension of cortical morphology (FD-CM). Furthermore, we explore the potential of these complexity measures to predict ECT treatment response. METHODS:Twenty patients with a current depressive episode (16 with major depressive disorder and 4 with bipolar disorder) underwent MRI-scans before and after an ECT-series. Twenty healthy controls matched for age and sex were also scanned twice for comparison purposes. Resting-state fMRI data were processed, and HFD was computed for anterior and posterior hippocampi. Group-by-time effects for HFD in anterior and posterior hippocampi were calculated and correlations between HFD changes and improvement in depression severity were examined. For FD-CM analyses, we preprocessed structural MRI with CAT12's surface-based methods. We explored group-by-time effects for FD-CM and the predictive value of baseline HFD and FD-CM for treatment outcome. RESULTS:Patients exhibited a significant increase in bilateral hippocampal HFD from baseline to follow-up scans. Right anterior hippocampal HFD increase was associated with reductions in depression severity. We found no group differences and group-by-time effects in FD-CM. After applying a whole-brain regression analysis, we found that baseline FD-CM in the left temporal pole predicted reduction of overall depression severity after ECT. Baseline hippocampal HFD did not predict treatment outcome. CONCLUSION:This study suggests that HFD and FD-CM are promising imaging markers to investigate ECT-induced neuroplasticity associated with treatment response.

Background: Individuals with spider phobic (SP) fear show hypervigilance and amygdala hyperactivity toward fear-associated stimuli, which may promote the development of other anxiety disorders. The amygdala is a key region within the fear network, which is connected to the anxiety system, where the bed nucleus of the stria terminalis (BNST) plays a crucial role. However, the BNST's involvement in phobic fear is unknown. Therefore, this study investigated the association of phobic fear and anxiety on these regions' functional connectivity (FC) in SP compared to healthy controls (HC).Methods: 7T-functional MRI resting-state FC of 30 individuals with SP and 45 HC was assessed to detect network differences between these groups. The association of phobic fear severity, trait anxiety, and social anxiety on FC was explored using linear regressions combined with seed-to-voxel analyses with amygdala and BNST as primary seeds, corrected for age and sex.Results: In SP, phobic fear was associated with reduced FC between the left amygdala and the right supramarginal gyrus. In contrast, anxiety severity was related to increased FC between the right BNST and the left inferior frontal gyrus. Moreover, social anxiety was related to decreased FC between bilateral BNST and left precuneus.Conclusions: These findings show changes in FC in SP, connecting fear with altered activity in the BNST and amygdala. The results suggest that persistent anxiety in phobic fear is associated with abnormal brain function in these regions, potentially explaining susceptibility to anxiety disorders and processes involved in phobic fear, such as threat perception, avoidance, and salience.Impact statement This is the first study to report altered FC mechanisms of BNST and amygdala in individuals with SP using 7T ultra-high field resting-state data. So far, only distinct characterization of brain regions, especially of BNST and amygdala, involved in those disorders exists. Our results contribute to closing this knowledge gap by providing the first evidence that deviant BNST and amygdala function in SP might elucidate the susceptibility to other anxiety disorders.

Psychomotor retardation, characterized by slowing of speech, thoughts, and a decrease of movements, is frequent in patients with major depressive disorder (MDD). However, its neurobiological correlates are still poorly understood. This study aimed to explore if cerebral blood flow (CBF) and resting state functional connectivity (rs-FC) of the motor network are altered in patients with MDD and if these changes are associated with psychomotor retardation. Thirty-six right-handed patients with depression and 19 right-handed healthy controls (HC) that did not differ regarding age and sex underwent arterial spin labelling (ASL) and resting-state functional MRI (rs-fMRI) scans. Psychomotor retardation was assessed with the motoric items of the core assessment of psychomotor change (CORE) questionnaire. Patients with MDD had more pronounced psychomotor retardation scores than HC. Patients with MDD had reduced CBF in bilateral cingulate motor area (CMA) and increased resting-state functional connectivity (rs-FC) between the cluster in the CMA and a cluster localized in bilateral supplementary motor areas (SMA). Furthermore, increased rs-FC between the CMA and the left SMA was associated with more pronounced psychomotor retardation. Our results suggest that reduced perfusion of the CMA and increased rs-FC between the CMA and the SMA are associated with psychomotor retardation in patients with depression.

BACKGROUND:A cognitively demanding, alcohol-specific inhibition training (Alc-IT) might enhance treatment success in patients with severe alcohol use disorder (AUD; Stein et al., 2023). An inhibitory working mechanism for Alc-IT has been discussed, but compelling evidence supporting this hypothesis is yet lacking. The present study investigates inhibitory performance during Alc-IT and examines whether inhibitory parameters mediate drinking outcome. METHODS:Patients with AUD (N = 232) completed six sessions of either a standard or improved Alc-IT, differing in their inhibitory demands determined by Go/NoGo-ratios in a modified Go-NoGo-task, or a control training. During these training sessions, data on inhibitory performance was collected. To assess differences in inhibitory performance and its improvement, alcohol-related errors of commission and relative performance, integrating accuracy and speed, were analyzed with hierarchical linear contrast models. Mediation analyses tested whether inhibitory performance predicted drinking outcome (percent days abstinent at 3-month follow-up). RESULTS:Patients in improved Alc-IT started with higher errors of commission (γ01(standard) =  -2.74, p < 0.001, R2 = 0.885) and a lower relative performance in the first training session compared to standard Alc-IT (γ01(standard) = 0.51, p = 0.004). They showed a steeper increase in relative performance until the final sixth session (γ1(s6),(standard) = -0.37, p = 0.024, R2 = 0.882). The effect of improved Alc-IT on drinking outcome was mediated by relative performance increase (bootstrap-CI [0.15, 7.11]). CONCLUSION:Higher inhibitory demands enable larger improvements across sessions. Mediation analysis supports an inhibitory working mechanism. Tailoring inhibitory demands to individual performance capacity could optimize future Alc-IT.

Childhood trauma (CT) often co-occurs with alcohol use disorder (AUD) and is associated with poor treatment outcome. We could demonstrated that patients with AUD and a history of childhood trauma showed reduced structural connectivity of the amygdala. Here, we additionally aimed to investigate fronto-limbic functional connectivity (FC) in patients with AUD with (AUD-CT) and without (AUD-noCT) CT. Based on findings in CT, we hypothesized reduced FC of the amygdala with the prefrontal cortex in AUD-CT and worse treatment outcome compared to AUD-noCT.Resting state fMRI scans were acquired in abstinent inpatients with AUD and healthy controls (HCs). We compared bilateral amygdala FC between AUD-CT (n = 21), AUD-noCT (n = 22), and HC (n = 27) using seed-based connectivity (SBC) and region-of-interest to region-of-interest (ROI-ROI) analysis. Sociodemographic and alcohol-specific variables (percent days abstinent, PDA) were assessed at treatment admission and three-month follow-up. The Childhood Trauma Questionnaire (CTQ) assessed trauma severity. SBC analysis revealed that AUD-CT showed increased FC of the left and right amygdala with the medial prefrontal cortex and left paracingulate gyrus compared to HC. AUD-CT showed increased ROI-ROI FC of the left with the right amygdala and the right amygdala with the medial prefrontal cortex. Moreover, AUD-CT exhibited a greater reduction of PDA at three-month follow-up compared to AUD-noCT.Increased FC of the amygdala, the medial prefrontal cortex, and paracingulate gyrus in AUD-CT might be a compensatory adaption to the reduced structural connectivity of the amygdala. Those specific alterations of FC in AUD-CT may represent a distinguishable neurobiological subtype of AUD, possibly underlying the complex clinical picture and worse treatment outcome.

Background:Increased mindfulness is associated with reduced alcohol consumption in patients with alcohol use disorder (AUD) after residential treatment. However, the underlying neurobiological mechanism of mindfulness in AUD is unclear. Therefore, we investigate the structural and functional alterations of the thalamocortical system with a focus on the mediodorsal thalamic nucleus (MD-TN), the default mode and the salience network (DMN/SN) which has previously been associated with mindfulness in healthy subjects. We hypothesized lower mindfulness and reduced structural and functional connectivity (FC) of the thalamocortical system, particularly in the DMN/SN in AUD. We assumed that identified neurobiological alterations in AUD are associated with impairments of mindfulness.Methods:Forty-five abstinent patients with AUD during residential treatment and 20 healthy controls (HC) were recruited. Structural and resting-state functional MRI-scans were acquired. We analysed levels of mindfulness, thalamic volumes and network centrality degree of the MD-TN using multivariate statistics. Using seed-based whole brain analyses we investigated functional connectivity (FC) of the MD-TN. We performed exploratory correlational analyses of structural and functional DMN/SN measurements with levels of mindfulness.Results:In AUD we found significantly lower levels of mindfulness, lower bilateral thalamic and left MD-TN volumes, reduced FC between MD-TN and anterior cingulum/insula and lower network centrality degree of the left MD-TN as compared to HC. In AUD, lower mindfulness was associated with various reductions of structural and functional aspects of the MD-TN.Conclusion:Our results suggest that structural and functional alterations of a network including the MD-TN and the DMN/SN underlies disturbed mindfulness in AUD.