Search

Objective: Enhanced reactivity to substance related cues is a central characteristic of addiction and has been associated with increased activity in motivation, attention, and memory related brain circuits and with a higher probability of relapse. Modafinil was promising in the first clinical trials in cocaine dependence, and was able to reduce craving in addictive disorders. However, its mechanism of action remains to be elucidated. In this functional magnetic resonance imaging (fMRI) study therefore, cue reactivity in cocaine dependent patients was compared to cue reactivity in healthy controls (HCs) under modafinil and placebo conditions.Methods: An fMRI cue reactivity study, with a double-blind, placebo-controlled cross-over challenge with a single dose of modafinil (200mg) was employed in 13 treatment seeking cocaine dependent patients and 16 HCs.Results: In the placebo condition, watching cocaine-related pictures (versus neutral pictures) resulted in higher brain activation in the medial frontal cortex, anterior cingulate cortex, angular gyrus, left orbitofrontal cortex, and ventral tegmental area (VTA) in the cocaine dependent group compared to HCs. However, in the modafinil condition, no differences in brain activation patterns were found between cocaine dependent patients and HCs. Group interactions revealed decreased activity in the VTA and increased activity in the right ACC and putamen in the modafinil condition relative to the placebo condition in cocaine dependent patients, whereas such changes were not present in healthy controls. Decreases in self-reported craving when watching cocaine-related cues after modafinil administration compared to the placebo condition were associated with modafinil-induced increases in ACC and putamen activation.Conclusions: Enhanced cue reactivity in the cocaine dependent group compared to healthy controls was found in brain circuitries related to reward, motivation, and autobiographical memory processes. In cocaine dependent patients, these enhanced brain responses were attenuated by modafinil, mainly due to decreases in cue- reactivity in reward-related brain areas (VTA) and increases in cue reactivity in cognitive control areas (ACC). These modafinil-induced changes in brain activation in response to cocaine-related visual stimuli were associated with diminished self-reported craving. These findings imply that in cocaine dependent patients, modafinil, although mainly known as a cognitive enhancer, acts on both the motivational and the cognitive brain circuitry. [ABSTRACT FROM AUTHOR]

Abnormal cue reactivity is a central characteristic of addiction, associated with increased activity in motivation, attention and memory related brain circuits. In this neuroimaging study, cue reactivity in problem gamblers (PRG) was compared with cue reactivity in heavy smokers (HSM) and healthy controls (HC). A functional magnetic resonance imaging event-related cue reactivity paradigm, consisting of gambling, smoking-related and neutral pictures, was employed in 17 treatment-seeking non-smoking PRG, 18 non-gambling HSM, and 17 non-gambling and non-smoking HC. Watching gambling pictures (relative to neutral pictures) was associated with higher brain activation in occipitotemporal areas, posterior cingulate cortex, parahippocampal gyrus and amygdala in PRG compared with HC and HSM. Subjective craving in PRG correlated positively with brain activation in left ventrolateral prefrontal cortex and left insula. When comparing the HSM group with the two other groups, no significant differences in brain activity induced by smoking cues were found. In a stratified analysis, the HSM subgroup with higher Fagerström Test for Nicotine Dependence scores (FTND M = 5.4) showed higher brain activation in ventromedial prefrontal cortex, rostral anterior cingulate cortex, insula and middle/superior temporal gyrus while watching smoking-related pictures (relative to neutral pictures) than the HSM subgroup with lower FTND scores (FTND M = 2.9) and than non-smoking HC. Nicotine craving correlated with activation in left prefrontal and left amygdala when viewing smoking-related pictures in HSM. Increased regional responsiveness to gambling pictures in brain regions linked to motivation and visual processing is present in PRG, similar to neural mechanisms underlying cue reactivity in substance dependence. Increased brain activation in related fronto-limbic brain areas was present in HSM with higher FTND scores compared with HSM with lower FTND scores. [ABSTRACT FROM AUTHOR]

BACKGROUND: Disinhibition and decision-making skills play an important role in theories on the cause and outcome of addictive behaviors such as substance use disorders and pathological gambling. In recent studies, both disinhibition and disadvantageous decision-making strategies, as measured by neurocognitive tests, have been found to influence the course of substance use disorders. Research on factors affecting relapse in pathological gambling is scarce.MethodThis study investigated the effect of both self-reported impulsivity and reward sensitivity, and neurocognitively assessed disinhibition and decision-making under conflicting contingencies, on relapse in a group of 46 pathological gamblers. RESULTS: Logistic regression analysis indicated that longer duration of the disorder and neurocognitive indicators of disinhibition (Stop Signal Reaction Time) and decision-making (Card Playing Task) were significant predictors of relapse (explaining 53% of the variance in relapse), whereas self-reported impulsivity and reward sensitivity did not significantly predict relapse. Overall classification accuracy was 76%, with a positive classification accuracy of 76% and a negative classification accuracy of 75%. CONCLUSIONS: Duration of the disorder and neurocognitive measures of disinhibition and decision-making are powerful predictors of relapse in pathological gambling. The results suggest that endophenotypical neurocognitive characteristics are more promising in the prediction of relapse in pathological gambling than phenotypical personality characteristics. Neurocognitive predictors may be useful to guide treatment planning of follow-up contacts and booster sessions. [ABSTRACT FROM AUTHOR]

We describe a patient with advanced Parkinson's disease who developed pathological gambling within a month after successful bilateral subthalamic nucleus (STN) stimulation. There was no history of gambling. On neuropsychological testing, slight cognitive decline was evident 1 year after surgery. Stimulation of the most dorsal contact with and without medication induced worse performances on decision making tests compared with the more ventral contact. Pathological gambling disappeared after discontinuation of pergolide and changing the stimulation parameters. Pathological gambling does not seem to be associated with decision making but appears to be related to a combination of bilateral STN stimulation and treatment with dopamine agonists. [ABSTRACT FROM AUTHOR]

BACKGROUND: Behavioral addictions like pathological gambling share many clinical characteristics with substance dependence. In addition, both types of disorders are associated with impairments in inhibitory control. Studies in patients with substance use disorders point to hyporesponsiveness of the dorsomedial prefrontal cortex. However, no such data exist on behavioral addictions. METHODS: Using functional magnetic resonance imaging, we investigated the neural circuitry associated with impaired response inhibition in a group of male problem gamblers (n=17) using a stop signal task. We included control conditions tailored to specifically isolate neural correlates of inhibitory control. To investigate the specificity of effects, a group of heavy smokers (n=18) and a group of healthy controls (n=17) were also included. RESULTS: Groups did not differ in behavioral performance on the stop signal task. However, both problem gamblers and heavy smokers showed hyporesponsiveness of the dorsomedial prefrontal cortex compared to healthy controls, during successful as well as failed response inhibition. These effects were robust against adjustments for depression and adult attention deficit scores. CONCLUSIONS: These findings suggest that hypoactivation of the inhibition circuit is a shared neural mechanism in substance use disorders and behavioral addictions. As such, they support the reclassification of pathological gambling as a behavioral addiction in DSM-V. [ABSTRACT FROM AUTHOR]

Objective: The association between depression and gambling disorder (GD) has been well-researched. However, prior research lacks consensus on the temporal association between depression and GD. Furthermore, the extant literature has not explored the nature of the aforementioned relationship using objective research methodology data and large-scale samples. The present study addressed these research gaps by investigating the longitudinal relationship between antidepressant prescriptions and the likelihood of developing GD using registry data over a period of 11 years (2008-2018)., Methods: Data were derived from the Norwegian Patient Registry (NPR) that was matched with data from the Norwegian Prescription Registry (NorPD). The dataset comprised 27,420 individuals, where 5,131 were diagnosed with GD. A binary logistic regression analysis was conducted where individuals with GD were compared with 22,289 individuals matched on age and gender from NPR., Results: The results show that individuals with antidepressant prescriptions had higher odds of developing GD (OR = 2.80, 95% CI: 2.60-3.01, p < 0.001). Furthermore, males and older adults were found to have a higher likelihood of being diagnosed with GD., Conclusions: Depression is known to be one of the most common mental health disorders. The findings show that prior antidepressant prescription is associated with GD, which would be in accordance with the escape hypothesis because some individuals gamble to escape dysphoric feelings, such as depression. The study findings add to the existing knowledge on the temporal association of depression and GD. Furthermore, the results also have significant practical implications.

Introduction: This study aimed to evaluate effects of three machine learning based adjustments made to an eHealth intervention for mild alcohol use disorder, regarding (a) early dropout, (b) participation duration, and (c) success in reaching personal alcohol use goals. Additionally, we aimed to replicate earlier machine learning analyses., Methods: We used three cohorts of observational log data from the Jellinek Digital Self-help intervention. First, a cohort before implementation of adjustments (T0; n = 320); second, a cohort after implementing two adjustments (i.e., sending daily emails in the first week and nudging participants towards a "no alcohol use" goal; T1; n = 146); third, a cohort comprising the prior adjustments complemented with eliminated time constraints to reaching further in the intervention (T2; n = 236)., Results: We found an increase in participants reaching further in the intervention, yet an increase in early dropout after implementing all adjustments. Moreover, we found that more participants aimed for a quit goal, whilst participation duration declined at T2. Intervention success increased, yet not significantly. Lastly, machine learning demonstrated reliability for outcome prediction in smaller datasets of an eHealth intervention., Conclusion: Strong correlates as indicated by machine learning analyses were found to affect goal setting and use of an eHealth program for alcohol use problems., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Background: For individuals who wish to reduce their cannabis use without formal help, there are a variety of self-help tools available. Although some are proven to be effective in reducing cannabis use, effect sizes are typically small. More insight into predictors of successful reduction of use among individuals who frequently use cannabis and desire to reduce/quit could help identify factors that contribute to successful cannabis use moderation., Methods: We analyzed data taken from a randomized controlled trial comparing the effectiveness of the digital cannabis intervention ICan to four online modules of educational information on cannabis. For the current study, we included 253 participants. Success was defined as reducing the grams of cannabis used in the past 7 days at baseline by at least 50 % at 6-month follow-up. To train and evaluate the machine learning models we used a nested k-fold cross-validation procedure., Results: The results show that the two models applied had comparable low AUROC values of .61 (Random Forest) and .57 (Logistic Regression). Not identifying oneself as a cannabis user, not using tobacco products, high levels of depressive symptoms, high levels of psychological distress and high initial cannabis use values were the relatively most important predictors for success, although overall the associations were not strong., Conclusions: Our study found only modest prediction accuracy when using machine learning models to predict success among individuals who use cannabis and desire to reduce/quit and show interest in digital self-help tools., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2024. Published by Elsevier B.V.)

Introduction: Somatic comorbidity is the main cause of reduced life expectancy in patients with substance use disorders (SUDs)., Aim: This study aims to investigate somatic health challenges in patients with SUDs using the USS. Patient self-management of somatic health and quality of life were also assessed., Method: In our study, a stratified random sample of 136 clients who received treatment at a specialist addiction facility was drawn to investigate their physical health and lifestyle behaviours using the Utrecht Somatic Screening 2.0 (USS 2.0). The sample included three subgroups, that is, patients receiving outpatient treatment through Flexible Assertive Community Treatment (FACT), Heroin-Assisted Treatment (HAT) and Opioid Replacement Therapy (ORT). Pain, self-management and quality of life were also measured. Descriptive statistics were used to analyse the data., Results: The findings indicate that many patients experience a large number of somatic health problems, including pain and exhaustion. The most prevalent conditions in this study are cardiovascular disease (25%) and COPD (20%), underweight and poor oral health. Tobacco smoking is prevalent among 88% of patients. Fifty percent of the patients expressed a need for support in managing their physical health., Implications for Practice: Somatic health care and lifestyle promotion should be tailored to the specific characteristics of patients., Conclusion: Patients with SUDs suffer from poor physical health and show unhealthy lifestyle behaviours, which demand the promotion of tailored somatic health., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

(1) Background: Ethnic minorities exhibit a higher prevalence of post-traumatic stress disorder (PTSD), while results for problematic substance use among ethnic groups remain mixed. PTSD and problematic substance use often co-occur; however, the impact of ethnicity on this association has not yet been investigated. (2) Methods: Self-report data on problematic alcohol/cannabis use (AUDIT/CUDIT) and presence of severe PTSD symptoms (PSS-SR) of N = 22,841 participants of Dutch ( n = 4610), South-Asian Surinamese ( n = 3306), African Surinamese ( n = 4349), Ghanaian ( n = 2389), Turkish ( n = 3947), and Moroccan ( n = 4240) origin were available from the HELIUS study. (3) Results: We found a positive association between the presence of severe PTSD symptoms and problematic alcohol and cannabis use. Ethnicity did not moderate the association between the presence of severe PTSD symptoms and problematic alcohol/cannabis use. (4) Conclusions: We demonstrated the relationship between the presence of severe PTSD symptoms and problematic alcohol/cannabis use in a multi-ethnic sample. The relationship between the presence of severe PTSD symptoms and problematic alcohol/cannabis use was similar between ethnic groups. We recommend screening for PTSD symptoms in those exhibiting problematic substance use and vice versa, regardless of ethnic background.

Background: Problematic drinking frequently co-occurs with depression among young adults, but often remains unaddressed in depression treatment. Evidence is insufficient on whether digital alcohol interventions can be effective in this young comorbid population. In a randomized controlled trial, we examined the effectiveness of Beating the Booze (BtB), an add-on digital alcohol intervention to complement depression treatment for young adults., Methods: Participants were randomized to BtB + depression treatment as usual (BTB + TAU, n = 81) or TAU ( n = 82). The primary outcome was treatment response, a combined measure for alcohol and depression after 6-month follow-up. Secondary outcomes were number of weekly drinks (Timeline Follow-back) and depressive symptoms (Center for Epidemiologic Studies Depression scale). Treatment response was analyzed using generalized linear modeling and secondary outcomes using robust linear mixed modeling., Results: Low treatment response was found due to lower than expected depression remission rates. No statistically significant between-group effect was found for treatment response after 6-month follow-up (odds ratio 2.86, p = 0.089, 95% confidence interval [CI] 0.85-9.63). For our secondary outcomes, statistically significant larger reductions in weekly drinks were found in the intervention group after 3-month ( B = -4.00, p = 0.009, 95% CI -6.97 to -1.02, d = 0.27) and 6-month follow-up ( B = -3.20, p = 0.032, 95% CI -6.13 to -0.27, d = 0.23). We found no statistically significant between-group differences on depressive symptoms after 3-month ( B = -0.57, p = 0.732, 95% CI -3.83 to 2.69) nor after 6-month follow-up ( B = -0.44, p = 0.793, 95% CI -3.69 to 2.82)., Conclusions: The add-on digital alcohol intervention was effective in reducing alcohol use, but not in reducing depressive symptoms and treatment response among young adults with co-occurring depressive disorders and problematic alcohol use., Trial Registration: Pre-registered on October 29, 2019 in the Overview of Medical Research in the Netherlands (OMON), formerly the Dutch Trial Register(https://onderzoekmetmensen.nl/en/trial/49219).

Background: Neurobiological characteristics have been identified regarding the severity of gambling disorder (GD). The aims of this study were: (1) to examine, through a path analysis, whether there was a relationship between neuroendocrine features, potentially mediational GD variables, and GD severity, and (2) to associate neuroendocrine variables, with GD severity-related variables according to gambling preferences., Methods: The sample included 297 outpatients with GD. We analyzed endocrine concentrations of different appetite-related hormones (ghrelin, liver antimicrobial peptide 2 [LEAP-2], leptin, adiponectin), and neuropsychological performance (working memory, cognitive flexibility, inhibition, decision making, premorbid intelligence). Path analysis assessed mechanisms between neuroendocrine features and GD severity, including mediational GD variables (impulsivity traits and gambling-related cognitive distortions). Partial correlations evaluated the associations between neuroendocrine variables, including impulsivity traits, and variables related to GD severity (DSM-5, South Oaks Gambling Screen, illness duration, and gambling-related cognitive distortions)., Results: Lower adiponectin concentrations predicted greater GD severity, while higher LEAP-2 concentrations predicted more gambling-related cognitive distortions. Likewise, better neuropsychological performance directly predicted GD severity, but worse neuropsychological performance was associated with GD severity through the mediational variables of impulsivity traits and gambling-related cognitive distortions. Also, in non-strategic individuals with GD, poor working memory was associated with gambling expectancies and predictive control. In strategic individuals with GD, poor cognitive flexibility was associated with illusion of control, predictive control, and inability to stop gambling., Conclusions: These results provide updated information about the comprehension of the interaction between neuroendocrine features, clinical variables, and severity of GD. Thus, neurobiological functions seem to be strongly related to GD severity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Importance: In the last 25 years, functional magnetic resonance imaging drug cue reactivity (FDCR) studies have characterized some core aspects in the neurobiology of drug addiction. However, no FDCR-derived biomarkers have been approved for treatment development or clinical adoption. Traversing this translational gap requires a systematic assessment of the FDCR literature evidence, its heterogeneity, and an evaluation of possible clinical uses of FDCR-derived biomarkers., Objective: To summarize the state of the field of FDCR, assess their potential for biomarker development, and outline a clear process for biomarker qualification to guide future research and validation efforts., Evidence Review: The PubMed and Medline databases were searched for every original FDCR investigation published from database inception until December 2022. Collected data covered study design, participant characteristics, FDCR task design, and whether each study provided evidence that might potentially help develop susceptibility, diagnostic, response, prognostic, predictive, or severity biomarkers for 1 or more addictive disorders., Findings: There were 415 FDCR studies published between 1998 and 2022. Most focused on nicotine (122 [29.6%]), alcohol (120 [29.2%]), or cocaine (46 [11.1%]), and most used visual cues (354 [85.3%]). Together, these studies recruited 19 311 participants, including 13 812 individuals with past or current substance use disorders. Most studies could potentially support biomarker development, including diagnostic (143 [32.7%]), treatment response (141 [32.3%]), severity (84 [19.2%]), prognostic (30 [6.9%]), predictive (25 [5.7%]), monitoring (12 [2.7%]), and susceptibility (2 [0.5%]) biomarkers. A total of 155 interventional studies used FDCR, mostly to investigate pharmacological (67 [43.2%]) or cognitive/behavioral (51 [32.9%]) interventions; 141 studies used FDCR as a response measure, of which 125 (88.7%) reported significant interventional FDCR alterations; and 25 studies used FDCR as an intervention outcome predictor, with 24 (96%) finding significant associations between FDCR markers and treatment outcomes., Conclusions and Relevance: Based on this systematic review and the proposed biomarker development framework, there is a pathway for the development and regulatory qualification of FDCR-based biomarkers of addiction and recovery. Further validation could support the use of FDCR-derived measures, potentially accelerating treatment development and improving diagnostic, prognostic, and predictive clinical judgments.

Introduction: The development of cocaine use disorder in females is suggested to be more strongly related to neural mechanisms underlying stress-reactivity, whereas in males it is suggested to be more strongly related to neural mechanisms underlying drug cue-reactivity. Existing evidence, however, is based on neuroimaging studies that either lack a control group and/or have very small sample sizes that do not allow to investigate sex differences., Methods: The main objective of the current study was to investigate sex differences in the neural correlates of cocaine and negative emotional cue-reactivity within high-risk intranasal cocaine users (CUs: 31 males and 26 females) and non-cocaine-using controls (non-CUs: 28 males and 26 females). A region of interest (ROI) analysis was applied to test for the main and interaction effects of group, sex, and stimulus type (cocaine cues vs. neutral cocaine cues and negative emotional cues vs. neutral emotional cues) on activity in the dorsal striatum, ventral striatum (VS), amygdala, and dorsal anterior cingulate cortex (dACC)., Results: There were no significant sex or group differences in cocaine cue-reactivity in any of the ROIs. Results did reveal significant emotional cue-reactivity in the amygdala and VS, but these effects were not moderated by group or sex. Exploratory analyses demonstrated that emotional cue-induced activation of the dACC and VS was negatively associated with years of regular cocaine use in female CUs, while this relationship was absent in male CUs., Conclusions: While speculative, the sex-specific associations between years of regular use and emotional cue-reactivity in the dACC and VS suggest that, with longer years of use, female CUs become less sensitive to aversive stimuli, including the negative consequences of cocaine use, which could account for the observed "telescoping effect" in female CUs., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Background: Childhood maltreatment (CM) can be divided into: emotional abuse (EA), physical abuse (PA), sexual abuse (SA), emotional neglect (EN), and physical neglect (PN). CM is associated with (Complex)Posttraumatic stress disorder (PTSD/CPTSD) and substance use disorder (SUD). Objective: This cross-sectional study examined the relationships between CM-subtypes with PTSD-severity and CPTSD in patients with SUD-PTSD. Method: Participants ( N = 209) were treatment-seeking SUD-PTSD patients who completed the Childhood Trauma Questionnaire-short form, the Clinician-Administered PTSD Scale for DSM-5 and the International Trauma Questionnaire. Regression analyses and a model selection procedure to select an optimal model were used to examine CM-subtypes as predictors of (C)PTSD, adjusted for sex and age. Results: Total CM and all CM-types significantly predicted PTSD-severity in the univariate regression analysis, with EA begin the strongest predictor. In the multiple regression only SA predicted PTSD-severity. Subsequently, model selection indicated that the optimal model to predict PTSD-severity included EA and SA. In the univariate analyses total CM, EA, and PN significantly predicted CPTSD-classification, and total CM and all CM-types significantly predicted CPTSD-severity. In the multiple regression for CPTSD-classification only EA and PA were significant predictors and for CPTSD-severity EA, PA and SA were significant predictors. In post-hoc multiple regression analyses, only EA was a significant predictor of CPTSD-classification and CPTSD-severity. Finally, in the model selection the most parsimonious model only included EA for both CPTSD-classification and CPTSD-severity. Sex was not a moderator in the relationship between CM and PTSD, nor in CM and CPTSD. Conclusions: These findings indicate that for SUD-PTSD patients, several CM-types have predictive value for (C)PTSD-severity, however SA and especially EA appear to contribute to these complaints. Since EA does not constitute an A-criterion, it is generally more overlooked in PTSD treatment. Its impact should therefore be underlined, and clinicians should be attentive to EA in their treatment.

Introduction: Over the past decade, frequent use of large quantities of nitrous oxide (N2O) has become more common in the Netherlands. Although N2O poses several negative health consequences for a subgroup of problematic N2O users, there is a lack of knowledge on what characterizes these intensive users. This study therefore aims to provide the demographic and substance use characteristics and experiences during treatment of treatment seeking problematic N2O users and to compare this with a matched group of treatment-seeking problematic cocaine users., Methods: A retrospective chart review was performed of patients who were referred for treatment of problematic N2O use at a large Dutch addiction care facility from January 2020 to September 2022, extracting demographics, pattern of use and follow-up data. Additionally, a subgroup of N2O users was propensity-score matched (1:1) with a subgroup of treatment seeking problematic cocaine users, both groups excluding users with substance use disorders or frequent use of substances other than N2O and cocaine, respectively., Results: 128 patients with a N2O use disorder were included in the total sample and a subgroup of 77 N2O-only users was propensity-score matched on age and sex to 77 cocaine-only users. N2O users were typically young (mean age 26.2 years), male (66.4%), unmarried (82.9%), with a low education level (59.0%) and born in the Netherlands (88.2%), with parents born in Morocco (45.3%). N2O was used intermittently (median 10 days/month, IQR 4.0-17.5 days) and often in very large quantities (median 5 kg [ca. 750 balloons] per average using day, IQR 2-10 kg). Compared to the patients with a cocaine use disorder, matched N2O users were lower educated, more often from Moroccan descent, and less likely to be alcohol or polysubstance users. Despite receiving similar treatments, N2O users were twice as likely to discontinue treatment before completion compared to cocaine users (63 vs. 35%, p = 0.004)., Conclusion: Treatment-seeking problematic N2O users are demographically different from treatment-seeking problematic cocaine users and are much more likely to dropout from psychological treatment. Further research is needed into the needs and other factors of problematic N2O users that relate to poor treatment adherence in problematic N2O users., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Background: The heterogeneity of gambling disorder (GD) has led to the identification of different subtypes, mostly including phenotypic features, with distinctive implications on the GD severity and treatment outcome. However, clustering analyses based on potential endophenotypic features, such as neuropsychological and neuroendocrine factors, are scarce so far., Aims: This study firstly aimed to identify empirical clusters in individuals with GD based on sociodemographic (i.e., age and sex), neuropsychological (i.e., cognitive flexibility, inhibitory control, decision making, working memory, attention, and set-shifting), and neuroendocrine factors regulating energy homeostasis (i.e., leptin, ghrelin, adiponectin, and liver-expressed antimicrobial peptide 2, LEAP-2). The second objective was to compare the profiles between clusters, considering the variables used for the clustering procedure and other different sociodemographic, clinical, and psychological features., Methods: 297 seeking-treatment adult outpatients with GD (93.6% males, mean age of 39.58 years old) were evaluated through a semi-structured clinical interview, self-reported psychometric assessments, and a protocolized neuropsychological battery. Plasma concentrations of neuroendocrine factors were assessed in peripheral blood after an overnight fast. Agglomerative hierarchical clustering was applied using sociodemographic, neuropsychological, and neuroendocrine variables as indicators for the grouping procedure. Comparisons between the empirical groups were performed using Chi-square tests (χ 2 ) for categorical variables, and analysis of variance (ANOVA) for quantitative measures., Results: Three-mutually-exclusive groups were obtained, being neuropsychological features those with the greatest weight in differentiating groups. The largest cluster (Cluster 1, 65.3%) was composed by younger males with strategic and online gambling preferences, scoring higher on self-reported impulsivity traits, but with a lower cognitive impairment. Cluster 2 (18.2%) and 3 (16.5%) were characterized by a significantly higher proportion of females and older patients with non-strategic gambling preferences and a worse neuropsychological performance. Particularly, Cluster 3 had the poorest neuropsychological performance, especially in cognitive flexibility, while Cluster 2 reported the poorest inhibitory control. This latter cluster was also distinguished by a poorer self-reported emotion regulation, the highest prevalence of food addiction, as well as a metabolic profile characterized by the highest mean concentrations of leptin, adiponectin, and LEAP-2., Conclusions: To the best of our knowledge, this is the first study to identify well-differentiated GD clusters using neuropsychological and neuroendocrine features. Our findings reinforce the heterogeneous nature of the disorder and emphasize a role of potential endophenotypic features in GD subtyping. This more comprehensive characterization of GD profiles could contribute to optimize therapeutic interventions based on a medicine of precision., Competing Interests: Declaration of Competing Interest Fernando Fernández-Aranda and Susana Jiménez-Murcia received consultancy honoraria from Novo Nordisk., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: There are growing concerns about commonly inflated effect sizes in small neuroimaging studies, yet no study has addressed recalibrating effect size estimates for small samples. To tackle this issue, we propose a hierarchical Bayesian model to adjust the magnitude of single-study effect sizes while incorporating a tailored estimation of sampling variance., Methods: We estimated the effect sizes of case-control differences on brain structural features between individuals who were dependent on alcohol, nicotine, cocaine, methamphetamine, or cannabis and non-dependent participants for 21 individual studies (Total cases: 903; Total controls: 996). Then, the study-specific effect sizes were modeled using a hierarchical Bayesian approach in which the parameters of the study-specific effect size distributions were sampled from a higher-order overarching distribution. The posterior distribution of the overarching and study-specific parameters was approximated using the Gibbs sampling method., Results: The results showed shrinkage of the posterior distribution of the study-specific estimates toward the overarching estimates given the original effect sizes observed in individual studies. Differences between the original effect sizes (i.e., Cohen's d) and the point estimate of the posterior distribution ranged from 0 to 0.97. The magnitude of adjustment was negatively correlated with the sample size (r = -0.27, p < 0.001) and positively correlated with empirically estimated sampling variance (r = 0.40, p < 0.001), suggesting studies with smaller samples and larger sampling variance tended to have greater adjustments., Discussion: Our findings demonstrate the utility of the hierarchical Bayesian model in recalibrating single-study effect sizes using information from similar studies. This suggests that Bayesian utilization of existing knowledge can be an effective alternative approach to improve the effect size estimation in individual studies, particularly for those with smaller samples., Competing Interests: RS has served on the scientific advisory board of Embera Neuro-therapeutics. DS has received research grants and/or consultancy honoraria from Lundbeck and Sun. MY has received funding from several law firms in relation to expert witness reports. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Cao, McCabe, Callas, Cupertino, Ottino-González, Murphy, Pancholi, Schwab, Catherine, Hutchison, Cousijn, Dagher, Foxe, Goudriaan, Hester, Li, Thompson, Morales, London, Lorenzetti, Luijten, Martin-Santos, Momenan, Paulus, Schmaal, Sinha, Solowij, Stein, Stein, Uhlmann, van Holst, Veltman, Wiers, Yücel, Zhang, Conrod, Mackey, Garavan and the ENIGMA Addiction Working Group.)

Background/objectives: The most important risk factor for recurrent pancreatitis after an episode of acute alcoholic pancreatitis is continuation of alcohol use. Current guidelines do not recommend any specific treatment strategy regarding alcohol cessation. The PANDA trial investigates whether implementation of a structured alcohol cessation support program prevents pancreatitis recurrence after a first episode of acute alcoholic pancreatitis., Methods: PANDA is a nationwide cluster randomised superiority trial. Participating hospitals are randomised for the investigational management, consisting of a structured alcohol cessation support program, or current practice. Patients with a first episode of acute pancreatitis caused by harmful drinking (AUDIT score >7 and < 16 for men and >6 and < 14 for women) will be included. The primary endpoint is recurrence of acute pancreatitis. Secondary endpoints include cessation or reduction of alcohol use, other alcohol-related diseases, mortality, quality of life, quality-adjusted life years (QALYs) and costs. The follow-up period comprises one year after inclusion., Discussion: This is the first multicentre trial with a cluster randomised trial design to investigate whether a structured alcohol cessation support program reduces recurrent acute pancreatitis in patients after a first episode of acute alcoholic pancreatitis, as compared with current practice., Trial Registration: Netherlands Trial Registry (NL8852). Prospectively registered., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Emerging evidence suggests distinct neurobiological correlates of alcohol use disorder (AUD) between sexes, which however remain largely unexplored. This work from ENIGMA Addiction Working Group aimed to characterize the sex differences in gray matter (GM) and white matter (WM) correlates of AUD using a whole-brain, voxel-based, multi-tissue mega-analytic approach, thereby extending our recent surface-based region of interest findings on a nearly matching sample using a complementary methodological approach. T1-weighted magnetic resonance imaging (MRI) data from 653 people with AUD and 326 controls was analyzed using voxel-based morphometry. The effects of group, sex, group-by-sex, and substance use severity in AUD on brain volumes were assessed using General Linear Models. Individuals with AUD relative to controls had lower GM volume in striatal, thalamic, cerebellar, and widespread cortical clusters. Group-by-sex effects were found in cerebellar GM and WM volumes, which were more affected by AUD in females than males. Smaller group-by-sex effects were also found in frontotemporal WM tracts, which were more affected in AUD females, and in temporo-occipital and midcingulate GM volumes, which were more affected in AUD males. AUD females but not males showed a negative association between monthly drinks and precentral GM volume. Our results suggest that AUD is associated with both shared and distinct widespread effects on GM and WM volumes in females and males. This evidence advances our previous region of interest knowledge, supporting the usefulness of adopting an exploratory perspective and the need to include sex as a relevant moderator variable in AUD., (© 2023 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Aims: To test the effectiveness of a digital intervention to reduce cannabis use (ICan) with adherence-focused guidance compared with educational cannabis information., Design: This was a single-blind randomized controlled trial. Follow-up clinical outcome measurements took place 3 and 6 months after randomization., Setting: The trial was conducted in the Netherlands. The intervention and guidance took place on-line, with recruitment via Facebook/Instagram advertisement campaigns., Participants: Inclusion criteria were ≥ 18 years, cannabis use on ≥ 3 days/week, the desire to reduce/quit cannabis and using a smartphone. Participants were allocated to either ICan (n = 188) or control (n = 190) (69% male, mean age = 27.5 years)., Intervention and Comparator: ICan is a mobile (web-)application based on motivational interviewing and cognitive behavioural therapy and includes three main components: screening, brief intervention (six modules) and referral to treatment. The control condition consisted of non-interactive educational cannabis information., Measurements: Primary outcome was the number of cannabis use days in the 7 days prior to the 6-month follow-up measurement. Secondary outcome measures at 3- and 6-month follow-up were the number of grams of cannabis used and attitudes towards seeking professional help for cannabis use related problems., Findings: Intention-to-treat analysis showed that 6 months after randomization the mean number of cannabis use days in the past 7 days was reduced in both conditions (time P < 0.001), with no significant group × time interaction effect [ICan = 4.17 days, control = 4.31 days, Cohen's d between  = 0.06, 95% confidence interval (CI) = -0.15, 0.26, P = 0.93]. Three months after randomization the mean number of grams used in the past 7 days was reduced in both conditions, with a significantly larger reduction in the ICan condition (P = 0.009, Cohen's d between  = 0.15). At 6-month follow-up the significant group × time interaction effect was no longer present (P = 0.30). In both conditions, attitudes towards seeking professional help remained virtually unchanged over time., Conclusions: A digital intervention to reduce cannabis use (ICan) was more effective than non-interactive educational cannabis information in reducing grams of cannabis used over 3 months, but not more effective at reducing cannabis use days at 6-month follow-up. Cannabis use reductions were maintained in both conditions between 3 and 6 months' follow-up., (© 2023 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.)

Aim: To explore the preferences of young adults with regard to the development of a new digital add-on alcohol intervention to complement depression treatment., Methods: This qualitative study included young adults (18-35 years) with experience of either problematic alcohol use or depression or both ( n  = 29). Two rounds of focus groups were conducted, with two focus groups in each round. All focus groups were recorded, transcribed and analysed deductively and inductively on the basis of qualitative content analysis of the intervention type, features and design., Results: Young adults preferred a mobile health application with a clear and simple objective and navigation which was also accessible on a computer. With regard to intervention features, participants indicated a preference for in-depth, gain-framed information on alcohol use and a main feature enabling them to record their alcohol use and mood, which would be rewarded. Other preferences included personal goal-setting and monitoring, an activity list, experience stories, peer contact, guidance from experts by experience or volunteers and receiving notifications from the application. In terms of design, participants preferred short, animated videos and animation figure illustrations to complement written text. Moreover, participants rated the design of the intervention as highly important, yet very personal. Generally, participants preferred a light pastel colour scheme. Once again, participants indicated a need for a clear dashboard using pictograms to reduce the amount of text and fast, easy-to-use navigation., Conclusion: The preferences indicated by young adults with regard to the intervention type, features and design may enhance the development of a new digital add-on alcohol intervention to complement depression treatment., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Introduction: Previous research has established co-occurrence between substance use disorders (SUDs) and gambling disorder (GD). Less well understood is the temporal sequencing of onset between these disorders, and in particular whether SUD is a risk factor for GD. The present study examined the temporal order between registered diagnoses of SUD and GD, stratified by sex., Methods: A study with a longitudinal design using objective registry data drawn from the Norwegian Patient Registry was carried out. Among the patients with a registered diagnosis of GD between 2008 and 2018 ( N  = 5,131; males = 81.8%), those (who in addition) had a registered diagnosis of any SUD ( n  = 1,196; males = 82.1%) were included. The measures included a registered diagnosis using the ICD-10 of both GD (code F63.0) and SUDs (codes F10-F19) by a health care professional. Binomial tests were used to identify the temporal order between SUD(s) and GD. Co-occurring cases (i.e., cases diagnosed within the same month) were removed in the main analyses., Results: Results showed a significant directional path from SUD to GD but no support for the reversed path (i.e., from GD to SUD). This finding was similar overall for (i) both males and females, (ii) when different SUDs (alcohol, cannabis, sedatives, and polysubstance) were examined individually, and (iii) when specifying a 12-month time-lag between diagnoses., Conclusions: The findings suggest that experiencing SUD(s) is a risk marker for GD given the temporal precedence observed for patients in specialised healthcare services seeking treatment. These results should be considered alongside screening and prevention efforts for GD., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: ‘The authors (except MDG) have no conflicts of interest relevant to this article to disclose. MDG has received research funding from Norsk Tipping (the gambling operator owned by the Norwegian government). MDG has received funding for a number of research projects in the area of gambling education for young people, social responsibility in gambling and gambling treatment from Gamble Aware (formerly the Responsibility in Gambling Trust), a charitable body which funds its research program based on donations from the gambling industry. MDG undertakes consultancy for various gambling companies in the area of social responsibility in gambling.’, (© 2023 The Author(s).)

Background and Aims: Dysfunction of the striatum, a brain region part of the mesolimbic reward system, is a key characteristic of addictive disorders, but neuroimaging studies have reported conflicting findings. An integrative model of addiction points to the presence or absence of addiction-related cues as an explanation for hyper- or hypoactivation, respectively, of the striatum., Methods: To test this model directly, we investigated striatal activation during monetary reward anticipation in the presence versus absence of addiction-related cues using functional MRI. Across two studies, we compared 46 alcohol use disorder (AUD) patients with 30 matched healthy controls; and 24 gambling disorder (GD) patients with 22 matched healthy controls., Results: During monetary reward anticipation, hypoactivation of the reward system was seen in AUD individuals compared to HCs. Additionally, a behavioral interaction was seen where gambling cues made participants, across groups, respond faster for bigger, but slower for smaller rewards. However, no striatal differences were seen in response to addiction-related cues between AUD or GD patients and their matched controls. Finally, despite substantial individual differences in neural activity to cue-reactivity and reward anticipation, these measures did not correlate, suggesting that they contribute independently to addiction aetiology., Discussion and Conclusions: Our findings replicate previous findings of blunted striatal activity during monetary reward anticipation in alcohol use disorder but do not support the idea that addiction-related cues explain striatal dysfunction as suggested by the model.

The development of addictive behaviors has been suggested to be related to a transition from goal-directed to habitual decision making. Stress is a factor known to prompt habitual behavior and to increase the risk for addiction and relapse. In the current study, we therefore used functional MRI to investigate the balance between goal-directed 'model-based' and habitual 'model-free' control systems and whether acute stress would differentially shift this balance in gambling disorder (GD) patients compared to healthy controls (HCs). Using a within-subject design, 22 patients with GD and 20 HCs underwent stress induction or a control condition before performing a multistep decision-making task during fMRI. Salivary cortisol levels showed that the stress induction was successful. Contrary to our hypothesis, GD patients did not show impaired goal-directed 'model-based' decision making, which remained similar to HCs after stress induction. Bayes factors provided three times more evidence against a difference between the groups or a group-by-stress interaction on the balance between model-based and model-free decision making. Similarly, no differences were found between groups and conditions on the neural estimates of model-based or model-free decision making. These results challenge the notion that GD is related to an increased reliance on habitual (or decreased goal-directed) control, even during stress., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Aims: The 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 <14 days of abstinence before treatment initiation (high-severity population) from other patients (mild-severity population). Treatment duration reflects the planned treatment duration. This study aimed to systematically investigate the effect of these potential effect moderators on SMO efficacy in alcohol-dependent patients., Methods: Network 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., Results: Eight 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 < 0.001. For PDA, longer treatment duration was associated with larger SMO effect size: +11.3% per extra month, P < 0.001. In the high-severity group, SMO showed benefit: abstinence rate RR 2.91, P = 0.03; PDA +16.9%, P < 0.001. In the mild-severity group, SMO showed benefit only in PDA for longer treatment duration: +23.9%, P < 0.001., Conclusions: In the retained studies with alcohol-dependent patients, high-severity population and longer treatment duration were associated with larger SMO effect sizes., (© The Author(s) 2023. Medical Council on Alcohol and Oxford University Press.)

Objective: Preventing and reducing violence is of high importance for both individuals and society. However, the overall efficacy of current treatment interventions aimed at reducing aggressive behavior is limited. New technological-based interventions may enhance treatment outcomes, for instance by facilitating out-of-session practice and providing just-in-time support. Therefore, the aim of this study was to assess the effects of the Sense-IT biocueing app as an addition to aggression regulation therapy (ART) on interoceptive awareness, emotion regulation, and aggressive behavior among forensic outpatients., Methods: A combination of methods was used. Quantitatively, a pretest-posttest design was applied to explore group changes in aggression, emotion regulation, and anger bodily sensations associated with the combination of biocueing intervention and ART. Measures were assessed at pretest, after 4 weeks posttest, and after one-month follow-up. During the 4 weeks, a single-case experimental ABA design was applied for each participant. Biocueing was added in the intervention phase. During all phases anger, aggressive thoughts, aggressive behavior, behavioral control, and physical tension were assessed twice a day, and heart rate was measured continuously. Qualitative information regarding interoceptive awareness, coping, and aggression was collected at posttest. 25 forensic outpatients participated., Results: A significant decrease in self-reported aggression was found between pre- and posttest. Furthermore, three-quarters of participants reported increased interoceptive awareness associated with the biocueing intervention. However, the repeated ambulatory measurements of the single-case experimental designs (SCEDs) did not indicate a clear effect favoring the addition of biocueing. On group level, no significant effects were found. On the individual level, effects favoring the intervention were only found for two participants. Overall, effect sizes were small., Conclusion: Biocueing seems a helpful addition to increase interoceptive awareness among forensic outpatients. However, not all patients benefit from the current intervention and, more specifically, from its behavioral support component aimed at enhancing emotion regulation. Future studies should therefore focus on increasing usability, tailoring the intervention to individual needs, and on integration into therapy. Individual characteristics associated with effective support by a biocueing intervention should be further investigated, as the use of personalized and technological-based treatment interventions is expected to increase in the coming years., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 ter Harmsel, Noordzij, van der Pol, Swinkels, Goudriaan and Popma.)