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Aims: Research over many years indicates that individuals with problematic alcohol or drug use or gambling disorders can cause considerable burden on family members. And yet, affected family members (AFMs) are largely neglected in research, health and social care policy and provision. To address the needs of AFMs of people struggling with a substance use or gambling disorder, the 5-Step Method was developed. Methods: The goal of this study is to evaluate the routinely delivered 5-Step Method in the Netherlands using measures at baseline (N = 145), and end-of-treatment (N = 102). In addition, a subsample at three-month post intervention (N = 70) was included. The intervention was delivered via video-conferencing to half (47.6%) of the participants. Findings: Participants reported significantly lower rates of Total Family Burden after completing the 5-Step Method, when comparing measurements at baseline and end-of-treatment (d = 0.56), and measurements at baseline and three-month post intervention (d = 0.85). In addition, participants following the intervention via video-conferencing (N = 69) performed equally well or better compared to participants following the intervention face-to-face (N = 76). Conclusions: Following the 5-Step Method for AFMs results in lower Total Family Burden. In accordance with the Stress-Strain-Information-Coping-Support (SSICS) model, the effectiveness of the intervention could be improved by finding new ways of increasing support for AFMs.

Aims This systematic review and meta-analysis assessed the effectiveness of digital interventions addressing depressive symptoms and alcohol use simultaneously among people with co-occurring depression and problematic alcohol use. Methods Seven databases were searched for trials evaluating digital interventions aimed at depression and alcohol use. Random-effects meta-analyses were conducted to pool effects on depressive symptoms and alcohol use up to 3-month and 6-month follow-up. Overall quality for every outcome was assessed with GRADE (Grading of Recommendations Assessment, Development and Evaluation). Results The pooled effect of digital interventions compared to their comparators was in favour of digital interventions. Small but significant effects on depressive symptoms at 3-month follow-up were found (g = 0.34, 95% confidence interval (CI): 0.06–0.62, P = 0.02, k = 6) and non-significant effects at 6-month follow-up (g = 0.29, 95% CI: −0.16 to 0.73, P = 0.15, k = 5). For alcohol use, the pooled effect of digital interventions was small and non-significant at 3-month follow-up (g = 0.14, 95% CI: −0.02 to 0.30, P = 0.07, k = 6) and significant at 6-month follow-up (g = 0.14, 95% CI: 0.07–0.20, P = 0.005, k = 5). Sensitivity analysis indicated the latter finding to be sensitive to statistical estimator choice. Quality of evidence was moderate, except for depressive symptoms at 6-month follow-up for which it was low. Conclusion Based on the literature, digital interventions are effective in reducing depressive symptoms at 3-month follow-up and alcohol use at 6-month follow-up among people with comorbid depression and problematic alcohol use. More high-quality trials are needed to confirm the current findings., Short Summary: Depression and problematic alcohol use often co-occur and are associated with negative outcomes. Digital interventions were found effective in reducing depressive symptoms at 3-month follow-up and alcohol use at 6-month follow-up among people with co-occurring depression and problematic alcohol use. More trials are needed to confirm the current evidence base.

Background Substance use disorders (SUDs) are prevalent in the general population, tend to follow a chronic course, are associated with many individual and social problems, and often have their onset in adolescence. However, the knowledge base from prospective population surveys and treatment-outcome studies on the course of SUD in adolescents is limited at best. The present study aims to fill this gap and focuses on a subgroup that is particularly at risk for chronicity: adolescents in addiction treatment. We will investigate the rate of persistent SUD and its predictors longitudinally from adolescence to young adulthood among youth with DSM-5 SUD from the start of their addiction treatment to 2 and 4 years following treatment-entry. In addition to SUD, we will investigate the course of comorbid mental disorders, social functioning, and quality of life and their association with SUD over time. Methods/design In a naturalistic, multi-center prospective cohort design, we will include youths (n = 420), who consecutively enter addiction treatment at ten participating organizations in the Netherlands. Inclusion is prestratified by treatment organization, to ensure a nationally representative sample. Eligible youths are 16 to 22 years old and seek help for a primary DSM-5 cannabis, alcohol, cocaine or amphetamine use disorder. Assessments focus on lifetime and current substance use and SUD, non-SUD mental disorders, family history, life events, social functioning, treatment history, quality of life, chronic stress indicators (hair cortisol) and neuropsychological tests (computerized executive function tasks) and are conducted at baseline, end of treatment, and 2 and 4 years post-baseline. Baseline data and treatment data (type, intensity, duration) will be used to predict outcome – persistence of or desistance from SUD. Discussion There are remarkably few prospective studies worldwide that investigated the course of SUD in adolescents in addiction treatment for longer than 1 year. We are confident that the Youth in Transition study will further our understanding of determinants and consequences of persistent SUD among high-risk adolescents during the critical transition from adolescence to young adulthood. Trial registration The Netherlands National Trial Register Trial NL7928. Date of registration January 17, 2019.

Aims There are indications that problematic alcohol use may negatively impact the course of major depressive disorder (MDD). However, most studies on alcohol use and adverse MDD outcomes are conducted amongst MDD populations with (severe) alcohol use disorder in psychiatric treatment settings. Therefore, it remains unclear whether these results can be generalised to the general population. In light of this, we examined the longitudinal relationship between alcohol use and MDD persistence after a 3-year follow-up amongst people with MDD from the general population. Methods Data were derived from the Netherlands Mental Health Survey and Incidence Study-2 (NEMESIS-2), a psychiatric epidemiological prospective study comprising four waves amongst the adult Dutch general population (n = 6.646). The study sample (n = 642) consisted of those with 12-month MDD who participated at the follow-up wave. The outcome was 12-month MDD persistence after the 3-year follow-up, which was assessed via the Composite International Diagnostic Interview version 3.0. Weekly alcohol consumption was operationalised as non-drinking (0 drinks), low-risk drinking (⩽7 drinks; reference), at-risk drinking (women 8–13 drinks, men 8–20 drinks) and high-risk drinking (women ⩾14, men ⩾21 drinks). We performed univariate and multiple logistic regression analyses, which were adjusted for various socio-demographic and health-related factors. Results The majority (67.4%) of the MDD sample were female, while the mean age was 47.1 years. Amongst these, 23.8% were non-drinkers, 52.0% were low-risk drinkers and 14.3% and 9.4% were at-risk and high-risk drinkers, respectively. Around one-quarter of the sample (23.6%) met the criteria for a persistent MDD after 3-year follow-up. No statistically significant association was found between alcohol use and MDD persistence, either for the crude model or the adjusted models. In comparison to low-risk drinking, the full adjusted model showed no statistically significant associations between MDD persistence and non-drinking (odds ratio (OR) = 1.15, p = 0.620), at-risk drinking (OR = 1.25, p = 0.423), or high-risk drinking (OR = 0.74, p = 0.501). Conclusions Contrary to our expectations, our findings showed that alcohol use was not a predictor of MDD persistence after 3-year follow-up amongst people with MDD from the general population.

Background For anorexia nervosa, firm evidence of the superiority of specialized psychological treatments is limited and economic evaluations of such treatments in real world settings are scarce. This consecutive cohort study examined differential (cost-)effectiveness for adult inpatients and outpatients with anorexia nervosa, after implementing cognitive behavioral therapy-enhanced (CBT-E) throughout a routine setting. Methods Differences in remission, weight regain and direct eating disorder treatment costs were examined between one cohort (N = 75) receiving treatment-as-usual (TAU) between 2012–2014, and the other (N = 88) CBT-E between 2015–2017. The economic evaluation was performed from a health care perspective with a one-year time horizon, using EDE global score Results Using direct eating disorder treatment costs in the cost-effectiveness analysis, the cost-effectiveness plane of the base case scenario for all patients indicated a 84% likelihood of CBT-E generating better health gain at additional costs. The median ICER is €51,081, indicating a probable preference for CBT-E (> 50% probability of cost-effectiveness) assuming a WTP of €51,081 or more for each additional remission, On remission, no difference was found with 9.3% remission during TAU and 14.6% during CBT-E (p = .304). Weight regain was higher during CBT-E (EMD = 1.33 kg/m2, SE = .29, 95% CI [0.76–1.9], p Conclusions In this mixed inpatient and outpatient cohort study, findings indicate a probability of CBT-Ebeing more effective at higher costs. These findings may contribute to the knowledge of effectiveness and cost-effectiveness of specialized psychological treatments. Plain English Summary In this study, the effectiveness and treatment costs of a specialized psychological treatment for adult clients with anorexia nervosa were compared with a regular, non-specialist treatment. One group of inpatients and outpatients did receive non-specialist treatment, the next group of inpatients and outpatients received CBT-E, a specialized treatment, later on. CBT-E is recommended for clients with bulimia and with binge eating disorder, for clients with anorexia nervosa it is less clear which specialized psychological treatment should be recommended. Results indicate that at end-of-treatment, CBT-E was not superior on remission. When looking at weight regain, CBT-E seemed superior than the treatment offered earlier. Economic evaluation suggests that CBT-E generates better health gain, but at additional costs. This study contributes to the knowledge on the effectiveness and treatment costs of psychological treatments, as they are offered in routine practice, to adults with anorexia nervosa.

Background: Sodium oxybate (SMO) has been shown to be effective in the maintenance of abstinence (MoA) in alcohol-dependent patients in a series of small randomized controlled trials (RCTs). These results needed to be confirmed by a large trial investigating the treatment effect and its sustainability after medication discontinuation. Aims: To confirm the SMO effect on (sustained) MoA in detoxified alcohol-dependent patients. Methods: Large double-blind, randomized, placebo-controlled trial in detoxified adult alcohol-dependent outpatients (80% men) from 11 sites in four European countries. Patients were randomized to 6 months SMO (3.3–3.9 g/day) or placebo followed by a 6-month medication-free period. Primary outcome was the cumulative abstinence duration (CAD) during the 6-month treatment period defined as the number of days with no alcohol use. Secondary outcomes included CAD during the 12-month study period. Results: Of the 314 alcohol-dependent patients randomized, 154 received SMO and 160 received placebo. Based on the pre-specified fixed-effect two-way analysis of variance including the treatment-by-site interaction, SMO showed efficacy in CAD during the 6-month treatment period: mean difference +43.1 days, 95% confidence interval (17.6–68.5; p = 0.001). Since significant heterogeneity of effect across sites and unequal sample sizes among sites ( n = 3–66) were identified, a site-level random meta-analysis was performed with results supporting the pre-specified analysis: mean difference +32.4 days, p = 0.014. The SMO effect was sustained during the medication-free follow-up period. SMO was well-tolerated. Conclusions: Results of this large RCT in alcohol-dependent patients demonstrated a significant and clinically relevant sustained effect of SMO on CAD. Trial registration: ClinicalTrials.gov Identifier: NCT04648423

AimsThe estimated effect of sodium oxybate (SMO) in the treatment of alcohol dependence is heterogeneous. Population severity and treatment duration have been identified as potential effect modifiers. Population severity distinguishes heavy drinking patients with MethodsNetwork meta-regression allows for testing potential effect modifiers. It was selected to investigate the effect of the above factors on SMO efficacy defined as continuous abstinence (abstinence rate) and the percentage of days abstinent (PDA). Randomized controlled trials for alcohol dependence with at least one SMO group conducted in high-severity and mild-severity populations were assigned to a high-severity and mild-severity group of studies, respectively.ResultsEight studies (1082 patients) were retained: four in the high-severity group and four in the mild-severity group. The high-severity group was associated with larger SMO effect sizes than the mild-severity group: abstinence rate risk ratio (RR) 3.16, P = 0.004; PDA +26.9%, P ConclusionsIn the retained studies with alcohol-dependent patients, high-severity population and longer treatment duration were associated with larger SMO effect sizes.

Young people, whose brains are still developing, might entail a greater vulnerability to the effects of alcohol consumption on brain function and development. A committee of experts of the Health Council of the Netherlands evaluated the state of scientific knowledge regarding the question whether alcohol negatively influences brain development in young people. A systematic literature search for prospective studies was performed in PubMed and PsychINFO, for longitudinal studies of adolescents or young adults ranging between 12 and 24 y of age at baseline, investigating the relation between alcohol use and outcome measures of brain structure and activity, cognitive functioning, educational achievement, or alcohol use disorder (AUD), with measures at baseline and follow-up of the outcome of interest. Data were extracted from original articles and study quality was assessed using the Newcastle-Ottawa Scale. A total of 77 studies were included, 31 of which were of sufficient quality in relation to the study objectives. There were indications that the gray matter of the brain develops abnormally in young people who drink alcohol. In addition, the more often young people drink or the younger they start, the higher the risk of developing AUD later in life. The evidence on white matter volume or quality, brain activity, cognitive function, and educational achievement is still limited or unclear. The committee found indications that alcohol consumption can have a negative effect on brain development in adolescents and young adults and entails a risk of later AUD. The committee therefore considers it a wise choice for adolescents and young adults not to drink alcohol.

In recent years, there has been a heightened interest in the effect of non-invasive brain stimulation on executive functioning. However, there is no comprehensive overview of its effects on different executive functioning domains in healthy individuals. Here, we assessed the state of the field by conducting a systematic review and meta-analysis on the effectiveness of non-invasive brain stimulation (i.e. repetitive transcranial magnetic stimulation and transcranial direct current stimulation) over prefrontal regions on tasks assessing working memory, inhibition, flexibility, planning and initiation performance. Our search yielded 63 studies (n = 1537), and the effectiveness of excitatory and inhibitory non-invasive brain stimulation were assessed per executive functioning task. Our analyses showed that excitatory non-invasive brain stimulation had a small but positive effect on Stop Signal Task and Go/No-Go Task performance, and that inhibitory stimulation had a small negative effect on Flanker Task performance. Non-invasive brain stimulation did not affect performance on working memory and flexibility tasks, and effects on planning tasks were inconclusive.

Purpose: Bariatric surgery is the most effective long-term treatment for sustained weight loss in obesity. Studies have shown that not all patients lose the expected amount of weight. The aim of this study was to develop a better understanding of which behavioral and psychological factors are associated with suboptimal weight loss. Methods: The present paper describes a cross-sectional study that included 140 participants. The mean follow-up period after bariatric surgery was 3.16 years. Eating disorder pathology (Eating Disorder Examination-Questionnaire), impulsivity (Barratt Impulsiveness scale-II) and depressive symptoms (Beck Depression Inventory) were compared with successful and suboptimal participants. A weight loss of more than or equal to 50% of excess weight, was considered to be successful. Results: More than 81% of the participants met the criterion for successful weight loss. The suboptimal weight loss group reported more symptoms of eating disorder pathology (p =.001), more loss of control over eating (p =.001), and more avoidant behavior due to poor body image (p

Previous studies have shown an association between the number of withdrawal attempts and increased severity of withdrawal symptoms in patients with an alcohol use disorder (AUD). An underlying allostatic neuroadaptive response may negatively affect the withdrawal pathology after alcohol discontinuation. The objective of the present research is to examine the intensification of psychiatric distress, craving, and post-detoxification drinking outcomes, which may result from these neurobehavioral alternations. Fifty-two AUD inpatients were divided into two groups

Objective: Economic evaluations of interventions for dual diagnosis patients are scarce. A recent randomized controlled trial has supported the effectiveness of the Self-wise, Otherwise, Streetwise (SOS) training to reduce victimization in dual diagnosis patients. The purpose of the current study was to analyze the cost-effectiveness and cost-utility of the SOS training as an add-on to care as usual (CAU). Methods: We performed an economic evaluation from a societal perspective alongside the SOS trial. Participants were 250 dual diagnosis patients recruited at three locations from a large urban psychiatric service in the Netherlands. The main outcomes were treatment response for victimization and quality-adjusted life years (QALYs). Both costs and effects were measured across a 14-month follow-up. Results: There was no significant difference between CAU + SOS and CAU in total costs (mean difference €4,859; 95% CI [−€4,795 to €14,513]) and QALY gains (mean difference 0.0012; 95% CI [−0.05 to 0.05]). Significantly more participants in CAU + SOS achieved treatment response for victimization compared to CAU (68% vs. 54%; mean difference 0.14; 95% CI [0.02 to 0.26]). The cost-effectiveness analysis indicated an 83% likelihood that CAU + SOS resulted in a higher treatment response rate for victimization at higher costs compared to CAU. The cost-utility analysis indicated that adding SOS-training to CAU is probably not cost-effective at conventional willingness-to-pay levels for QALYs. Conclusions: At a societal willingness-to-pay of €38,000 or more per extra treatment responder, adding SOS-training to usual care is probably more attractive than usual care alone with regard to cost-effectiveness. This is a considerable willingness to pay. However, the direct costs of offering the SOS training are expected to be minor. Our findings should be interpreted with caution due to the short follow-up period and absence of data on potential reductions in police and judicial costs other than prison costs.

© 2020 The AuthorsOver the last years, biofeedback applications are increasingly used to enhance interoceptive awareness and self-regulation, in psychiatry and beyond. These applications are used to strengthen emotion regulation skills by home training (ambulatory biofeedback) and real-time support in everyday life stressful situations (biocueing). Unfortunately, knowledge about the feasibility and effectivity of these applications is still scarce. Therefore, a systematic literature search was performed. In total, 30 studies (4 biocueing, 26 ambulatory biofeedback) were reviewed; 21 of these studies were conducted in non-psychiatric samples and 9 studies in psychiatric samples. Study characteristics, biofeedback characteristics, effectivity and feasibility outcomes were extracted. Despite the rapid advances in wearable technology, only a few biocueing studies were found. In the majority of the studies significant positive effects were found on self-reported (stress-related) psychological measures. Significant improvements on physiological measures were also reported, though these measures were used less frequently. Feasibility of the applications was often reported as sufficient, though not adequately assessed in most studies. Taken into account the small sample sizes and the limited quality of the majority of the studies in this recently emerging field, biocueing and ambulatory biofeedback interventions showed promising results. Future research is expected to be focusing on biocueing as a just-in-time adaptive intervention. To establish this research field, closer cooperation between research groups, use of more rigorous as well as individually tailored research designs and more valid feasibility and effectivity assessment are recommended.

Contains fulltext : 219494.pdf (Publisher’s version ) (Closed access) While imaging studies have demonstrated volumetric differences in subcortical structures associated with dependence on various abused substances, findings to date have not been wholly consistent. Moreover, most studies have not compared brain morphology across those dependent on different substances of abuse to identify substance-specific and substance-general dependence effects. By pooling large multinational datasets from 33 imaging sites, this study examined subcortical surface morphology in 1628 nondependent controls and 2277 individuals with dependence on alcohol, nicotine, cocaine, methamphetamine, and/or cannabis. Subcortical structures were defined by FreeSurfer segmentation and converted to a mesh surface to extract two vertex-level metrics - the radial distance (RD) of the structure surface from a medial curve and the log of the Jacobian determinant (JD) - that, respectively, describe local thickness and surface area dilation/contraction. Mega-analyses were performed on measures of RD and JD to test for the main effect of substance dependence, controlling for age, sex, intracranial volume, and imaging site. Widespread differences between dependent users and nondependent controls were found across subcortical structures, driven primarily by users dependent on alcohol. Alcohol dependence was associated with localized lower RD and JD across most structures, with the strongest effects in the hippocampus, thalamus, putamen, and amygdala. Meanwhile, nicotine use was associated with greater RD and JD relative to nonsmokers in multiple regions, with the strongest effects in the bilateral hippocampus and right nucleus accumbens. By demonstrating subcortical morphological differences unique to alcohol and nicotine use, rather than dependence across all substances, results suggest substance-specific relationships with subcortical brain structures. 15 p.

The neurobiological bases of the association between development and psychopathology remain poorly understood. Here, we identify a shared spatial pattern of cortical thickness (CT) in normative development and several psychiatric and neurological disorders. Principal component analysis (PCA) was applied to CT of 68 regions in the Desikan-Killiany atlas derived from three large-scale datasets comprising a total of 41,075 neurotypical participants. PCA produced a spatially broad first principal component (PC1) that was reproducible across datasets. Then PC1 derived from healthy adult participants was compared to the pattern of CT differences associated with psychiatric and neurological disorders comprising a total of 14,886 cases and 20,962 controls from seven ENIGMA disease-related working groups, normative maturation and aging comprising a total of 17,697 scans from the ABCD Study® and the IMAGEN developmental study, and 17,075 participants from the ENIGMA Lifespan working group, as well as gene expression maps from the Allen Human Brain Atlas. Results revealed substantial spatial correspondences between PC1 and widespread lower CT observed in numerous psychiatric disorders. Moreover, the PC1 pattern was also correlated with the spatial pattern of normative maturation and aging. The transcriptional analysis identified a set of genes including KCNA2, KCNS1 and KCNS2 with expression patterns closely related to the spatial pattern of PC1. The gene category enrichment analysis indicated that the transcriptional correlations of PC1 were enriched to multiple gene ontology categories and were specifically over-represented starting at late childhood, coinciding with the onset of significant cortical maturation and emergence of psychopathology during the prepubertal-to-pubertal transition. Collectively, the present study reports a reproducible latent pattern of CT that captures interregional profiles of cortical changes in both normative brain maturation and a spectrum of psychiatric disorders. The pubertal timing of the expression of PC1-related genes implicates disrupted neurodevelopment in the pathogenesis of the spectrum of psychiatric diseases emerging during adolescence.

A growing body of evidence suggests that, during decision-making, BOLD signal in the ventromedial prefrontal cortex (VMPFC) correlates both with motivational variables – such as incentives and expected values – and metacognitive variables – such as confidence judgments – which reflect the subjective probability of being correct. At the behavioral level, we recently demonstrated that the value of monetary stakes bias confidence judgments, with gain (respectively loss) prospects increasing (respectively decreasing) confidence judgments, even for similar levels of difficulty and performance. If and how this value-confidence interaction is reflected in the VMPFC remains unknown. Here, we used an incentivized perceptual decision-making fMRI task that dissociates key decision-making variables, thereby allowing to test several hypotheses about the role of the VMPFC in the value-confidence interaction. While our initial analyses seemingly indicate that the VMPFC combines incentives and confidence to form an expected value signal, we falsified this conclusion with a meticulous dissection of qualitative activation patterns. Rather, our results show that strong VMPFC confidence signals observed in trials with gain prospects are disrupted in trials with no – or negative (loss) – monetary prospects. Deciphering how decision variables are represented and interact at finer scales seems necessary to better understand biased (meta)cognition.

While it has been suggested that cocaine use and relapse in women is more strongly related to stress-relief craving, whereas cocaine use in men is more strongly related to reward craving, the neural mechanisms that underlie these differences are poorly understood. The aim of this study was to investigate sex-dependent differences in insular morphometry and associations with craving, in a sample of regular cocaine users (CUs) and non-drug using controls (non-CUs). It was hypothesized that insular volume, thickness and surface area would be lower in CU women, compared with CU men and non-CUs. It was furthermore hypothesized that insular morphometry, particularly insular thickness, would be negatively associated to reward craving in CU men, while being negatively associated with stress-relief craving in CU women. In contrast to the hypothesis, we did not find evidence of sex-specific differences in insular morphometry in CUs. However, sex-specific association between stress-relief craving and insular morphometry were found: Right insular volume was negatively associated with stress-relief craving in CU women, whereas this association was positive in CU men. Additionally, right insular surface area was negatively associated with stress-relief craving in cocaine-using men, whereas this association was positive in cocaine-using women. In conclusion, the current study provides first evidence of sex-specific differences in the association between craving and insular morphometry in a sample of regular cocaine users. Although speculative, these sex-specific alterations in insular morphometry may underlie higher stress-induced craving and relapse in CU women compared with CU men.

Substance use disorders (SUDs) and borderline personality disorder (BPD) are highly comorbid. In the present study, an attempt was made to understand the differences between BPD and BPD with comorbid SUD (BPD + alcohol use disorder [AUD]), by studying impulsivity and schema modes (i.e., maladaptive moment-to-moment emotional states and coping responses). BPD patients, BPD+AUD patients, and nonpatients (NP) were compared regarding behavioral impulsivity (motor impulsivity, risk taking, delay discounting), and schema modes. The two patient groups displayed greater delay discounting than the NP group. Further, BPD and BPD+AUD groups were different from the NP group regarding all schema modes investigated. However, no differences were found on any of the dependent variables between the two patient groups. It is suggested that although BPD patients are in general more impulsive and have more maladaptive moment-to-moment emotional states and coping responses, BPD patients with and without AUD seem not to be different in this respect.

Alcohol use disorder is argued to be a highly complex disorder influenced by a multitude of factors on different levels. Common research approaches fail to capture this breadth of interconnecting symptoms. To address this gap in theoretical assumptions and methodological approaches, we used a network analysis to assess the interplay of alcohol use disorder symptoms. We applied the exploratory analysis to two US-datasets, a population sample with 23,591 individuals and a clinical sample with 483 individuals seeking treatment for alcohol use disorder. Using a Bayesian framework, we first investigated differences between the clinical and population sample looking at the symptom interactions and underlying structure space. In the population sample the time spent drinking alcohol was most strongly connected, whereas in the clinical sample loss of control showed most connections. Furthermore, the clinical sample demonstrated less connections, however, estimates were too unstable to conclude the sparsity of the network. Second, for the population sample we assessed whether the network was measurement invariant across external factors like age, gender, ethnicity and income. The network differed across all factors, especially for age subgroups, indicating that subgroup specific networks should be considered when deriving implications for theory building or intervention planning. Our findings corroborate known theories of alcohol use disorder stating loss of control as a central symptom in alcohol dependent individuals.

Cue reactivity measured by functional magnetic resonance imaging is used in studies of substance-use disorders. This Consensus Statement is the result of a Delphi process to arrive at parameters that should be reported in describing these studies. Cue reactivity is one of the most frequently used paradigms in functional magnetic resonance imaging (fMRI) studies of substance use disorders (SUDs). Although there have been promising results elucidating the neurocognitive mechanisms of SUDs and SUD treatments, the interpretability and reproducibility of these studies is limited by incomplete reporting of participants characteristics, task design, craving assessment, scanning preparation and analysis decisions in fMRI drug cue reactivity (FDCR) experiments. This hampers clinical translation, not least because systematic review and meta-analysis of published work are difficult. This consensus paper and Delphi study aims to outline the important methodological aspects of FDCR research, present structured recommendations for more comprehensive methods reporting and review the FDCR literature to assess the reporting of items that are deemed important. Forty-five FDCR scientists from around the world participated in this study. First, an initial checklist of items deemed important in FDCR studies was developed by several members of the Enhanced NeuroImaging Genetics through Meta-Analyses (ENIGMA) Addiction working group on the basis of a systematic review. Using a modified Delphi consensus method, all experts were asked to comment on, revise or add items to the initial checklist, and then to rate the importance of each item in subsequent rounds. The reporting status of the items in the final checklist was investigated in 108 recently published FDCR studies identified through a systematic review. By the final round, 38 items reached the consensus threshold and were classified under seven major categories: Participants Characteristics, General fMRI Information, General Task Information, Cue Information, Craving Assessment Inside Scanner, Craving Assessment Outside Scanner and Pre- and Post-Scanning Considerations. The review of the 108 FDCR papers revealed significant gaps in the reporting of the items considered important by the experts. For instance, whereas items in the General fMRI Information category were reported in 90.5% of the reviewed papers, items in the Pre- and Post-Scanning Considerations category were reported by only 44.7% of reviewed FDCR studies. Considering the notable and sometimes unexpected gaps in the reporting of items deemed to be important by experts in any FDCR study, the protocols could benefit from the adoption of reporting standards. This checklist, a living document to be updated as the field and its methods advance, can help improve experimental design, reporting and the widespread understanding of the FDCR protocols. This checklist can also provide a sample for developing consensus statements for protocols in other areas of task-based fMRI. Funding Agencies|National Institute on Alcohol Abuse and Alcoholism (NIAAA)United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Alcohol Abuse & Alcoholism (NIAAA) [P50 AA010761]; Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)German Research Foundation (DFG) [402170461-TRR 265, 40217046-TRR 265, 421888313, 437718741, 324164820]; DFGGerman Research Foundation (DFG)European Commission [402170461 - TRR 265]; California Tobacco-Related Disease Research Grant Program of the University of California [T30IP0962]; Laureate Institute for Brain Research (LIBR); Warren K. Family Foundation; Oklahoma Center for Advancement of Science and Technologies (OCAST) [HR18-139]; Brain and Behavior Foundation (NARSAD Young Investigator Award) [27305]; National Institute on Drug Abuse (NIDA)United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Drug Abuse (NIDA) [R01 DA030344, R21DA044465]; NIDAUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Drug Abuse (NIDA) [R01DA041528, R01DA048301, R01DA047851, K23DA042898, K12 DA000167, U01 DA041089, U24 DA041147, P30 DA048742]; NCCIH [R01AT010627]; NIAAAUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Alcohol Abuse & Alcoholism (NIAAA) [F32AA027699, R01 AA027765, R01 AA026859, U01 AA021692, U24 AA021695, R01AA023665, R01AA022328]; NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R01DA039135, K02DA042987, R01 DA041866, R01AA026844, K08AA023545, K23AA023894, R01DA040670, R21HL144673, R01DA041438, R21DA045853]; Bundesministerium fur Bildung und ForschungFederal Ministry of Education & Research (BMBF) [FKZ: 01ZX1503, 01ZX1909B]; Shanghai Municipal Science and Technology Major project [2019SHZDZX02]; Eli Lilly Canada Chair on schizophrenia researchEli Lilly; Australian Medical Research Future FundMedical Research Future Fund (MRFF) [MRF1141214]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81871426]

This study tested the effectiveness of schema therapy (ST) for borderline personality disorder (BPD) and comorbid alcohol dependence (AD). Twenty patients participated in a case series study with multiple baselines. The baseline phase consisted of treatment as usual. It was followed by a case conceptualization phase, an experiential techniques phase and a behavioural change phase. Patients showed a significant decrease in BPD and AD symptoms; change was mainly accomplished in the experiential techniques phase, with medium to large effect sizes. Three months after termination of therapy, 68% of the patients had remitted from BPD, and the number of drinking days decreased clearly. This study shows that, although treatment is challenging in this group of patients, meaningful change can be obtained in patients with BPD and AD using ST.

Aims: Compulsivity is a common phenotype among psychiatric disorders, such as obsessive–compulsive disorder (OCD) and gambling disorder (GD). Deficiencies in metacognition, such as the inability to estimate one's performance via confidence judgments could contribute to pathological decision-making. Earlier research has shown that patients with OCD exhibit underconfidence, while patients with GD exhibit overconfidence. Moreover, it is known that motivational states (e.g. monetary incentives) influence metacognition, with gain (respectively loss) prospects increasing (respectively decreasing) confidence. Here, we reasoned that OCD and GD symptoms might correspond to an exacerbation of this interaction between metacognition and motivation. Methods: We hypothesized GD's overconfidence to be exaggerated during gain prospects, while OCD's underconfidence to be worsened in loss context, which we expected to see represented in ventromedial prefrontal cortex (VMPFC) blood-oxygen-level-dependent activity. We tested those hypotheses in a task-based functional magnetic resonance imaging (fMRI) design (27 patients with GD, 28 patients with OCD, 55 controls). The trial is registered in the Dutch Trial Register (NL6171). Results: We showed increased confidence for patients with GD versus patients with OCD, which could partly be explained by sex and IQ. Although our primary analyses did not support the hypothesized interaction between incentives and groups, exploratory analyses did show increased confidence in patients with GD specifically in gain context. fMRI analyses confirmed a central role for VMPFC in the processing of confidence and incentives, but no differences between the groups. Conclusion: Patients with OCD and those with GD reside at opposite ends of the confidence spectrum, while no interaction with incentives was found, nor group differences in neuronal processing of confidence.

Background Depressive disorders and problematic drinking often co-occur, also among young adults. These co-occurring conditions are associated with various negative health outcomes compared to both conditions alone. Early intervention by addressing alcohol use and depressive symptoms simultaneously in the same treatment might improve both conditions. However, evidence on the (cost-) effectiveness of digital combined depression and alcohol interventions for young adults is currently insufficient. We therefore developed an add-on digital alcohol moderation adherence-focussed guided intervention to complement treatment as usual (TAU) for depressive disorders. The digital intervention is a web-app, including 6 modules based on motivational interviewing and cognitive behavioural therapy. This study aims to evaluate the (cost-)effectiveness of a digital alcohol moderation intervention + TAU compared to TAU on alcohol and depression outcomes among young adults with co-occurring depressive disorders and problematic alcohol use. Methods One hundred fifty-six participants, aged 18–35 years, with problematic alcohol use and a diagnosed depressive disorder will participate in a pragmatic multicentre two-arm randomized controlled trial. Problematic alcohol use is operationalised as scoring ≥5 for women and ≥ 8 for men on the Alcohol Use Disorder Identification Test (AUDIT). Participants will be randomized to either the experimental group (digital alcohol intervention + TAU) or control group (TAU only). Participants will be recruited at three Dutch mental health care centres and through social media. Assessments take place at baseline and after 3, 6 and 12 months post-randomization. The primary outcome is treatment response at 6-month follow-up, operationalized as a composite score that combines alcohol use and depression measures and indicates whether treatment has been successful or not. Secondary outcomes are depressive symptoms and alcohol use (i.e. number of weekly standard drinks and AUDIT score). An economic evaluation will be conducted alongside the trial. Discussion This study evaluates the (cost-) effectiveness of an add-on digital alcohol moderation intervention for young adults who are in treatment for depressive disorders. If proven effective, the digital intervention could be implemented in mental health care and improve treatment for people with co-occurring depressive disorders and problematic alcohol use. Trial registration Pre-registered on October 29, 2019 in The Netherlands Trial Register (NL8122).

Background Heavy cannabis use is associated with adverse physical and mental health effects. Despite available effective treatments, the majority of heavy cannabis users does not seek professional help. Web-based interventions can provide an alternative for cannabis users who are reluctant to seek professional help. Several web-based cannabis interventions are effective in reducing cannabis use; however, the effect sizes are typically small and attrition rates are typically high. This suggests that web-based programs can be an effective cannabis use intervention for some, while others may need additional substance use treatment after completing a web-based intervention. Therefore, it is important that web-based interventions do not solely focus on reducing cannabis use, but also on improving attitudes towards substance use treatment. The Screening Brief Intervention and Referral to Treatment (SBIRT) approach appears to be well suited for the purpose of reducing cannabis use and improving substance use treatment utilization. Based on the SBIRT approach—and based on cognitive behavioral therapy (CBT) and motivational interviewing (MI)—we developed the Internet-based cannabis reduction intervention ICan. Methods/design This protocol paper presents the design of a randomized controlled trial (RCT) in which we evaluate the effectiveness of the ICan intervention compared to four online modules of educational information on cannabis in a sample of Dutch frequent cannabis users. The primary outcome measure is frequency of cannabis use. Secondary outcome measures include the quantity of cannabis used (grams), the attitudes towards seeking help and the number of participants who enter specialized treatment services for cannabis use-related problems. Discussion To the best of our knowledge, ICan is the first Internet-based intervention for cannabis users that combines screening, a brief intervention—based on CBT and MI—and referral to treatment options. Trial registration The study is registered in the Netherlands Trial Register; identifier NL7668. Registered on 17 April 2019.

Background: The majority of people with cannabis use disorder do not seek treatment. If we were able to gain more insight into different subgroups of cannabis users based on help-seeking preferences, we could use this information to inform the development and promotion of interventions targeted at specific subgroups of cannabis users, to ultimately narrow the treatment gap. Methods: An online survey was conducted among 1,015 Dutch frequent cannabis users (18–72 years) to assess their cannabis use, help-seeking preferences, psychopathology, and psychological distress. Latent class analysis was used to identify classes of cannabis users based on their help-seeking preferences. Differences between the identified classes in terms of sociodemographics, cannabis use, and psychopathology were examined. Results: We identified four classes with distinct preferences for support. Class 1 (“no support/only social,” n = 548) had a low probability of finding any form of support appealing other than social support. Class 2 (“online help,” n = 170) had relatively high probabilities of finding online help appealing. Class 3 (“GP/outpatient,” n = 208) had a relatively high probability of finding support from the general practitioner and outpatient substance use disorder treatment appealing. Class 4 (“all sources,” n = 89) had moderate to high probabilities for all sources of support. In terms of sociodemographics, differences between the classes were found with regard to gender and level of education. The classes were fairly similar with regard to cannabis use, only the “online help” class scored significantly lower on both cannabis use frequency and quantity compared to most of the other classes. In terms of psychopathology, the “GP/outpatient” class and the “all sources” class experienced more cannabis use-related problems and were more likely to report multiple past quit attempts than the “online help” class and the “no support/only social” class. Conclusions: Our study shows that there is a lot of inter-individual variation in how appealing various forms of help are to cannabis users. Our findings emphasize the importance of promoting a variety of treatment modalities for cannabis users, including real-life and digital options, and indicate what might appeal to whom.

IntroductionCurrent treatments for cocaine use disorder (CUD) are not very effective and better treatments are needed. This study investigates the effectiveness of a combined intervention that targets the assumed underlying glutamate pathology in cocaine users. To this end, the combined effects of N-acetylcysteine (NAC) and working memory (WM) training on glutamate concentrations in the dorsal and rostral ACC were investigated in a randomized, double-blind placebo-controlled design.MethodsIn this study, 38 regular cocaine-using men were randomized to either 25-days with 2400 mg/day NAC and WM-training or 25 days with placebo with WM-training. Cocaine use, impulsivity, and glutamate concentrations in the dACC and rACC using proton Magnetic Resonance Spectroscopy were assessed at baseline and after treatment.ResultsTwenty-four participants completed the study, of which 9 received NAC and 15 received placebo. There were no baseline correlations of glutamate concentrations in the dACC or rACC with cocaine use measures or impulsivity. Additionally, there were no effects of NAC, WM-training, or the combination thereof on (changes in) glutamate concentrations in the dACC or rACC.DiscussionThis randomized proof of concept study could not confirm our hypotheses. Possible explanations are insufficient power and the possible absence of deviant baseline glutamate concentrations in the included participants. Future studies should consider larger samples and a non-using control group to confirm baseline deviations in glutamate in cocaine users.