Cortical profiles of numerous psychiatric disorders and normal development share a common pattern.

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.

Cluster analysis in gambling disorder based on sociodemographic, neuropsychological, and neuroendocrine features regulating energy homeostasis.

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 (χ2) 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.

Sex-Dependent Differences in the Neural Correlates of Cocaine and Emotional Cue-Reactivity in Regular Cocaine Users and Non-Drug-Using Controls: Understanding the Role of Duration and Severity of Use.

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.

Treatment Seeking Nitrous Oxide Users in Addiction Care: A Comparison with Cocaine Users on Clinical and Treatment Characteristics.

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.

Brain volumes in alcohol use disorder: Do females and males differ? A whole-brain magnetic resonance imaging mega-analysis.

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.

Sodium Oxybate for Alcohol Dependence: A Network Meta-Regression Analysis Considering Population Severity at Baseline and Treatment Duration.

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.

Accuracy of the Depression, Anxiety and Stress Scale (DASS-21) for Screening on Comorbid Internalizing Disorders among Youth in Substance Use Disorder Treatment.

INTRODUCTION: Major depression, anxiety disorders, and post-traumatic stress disorder (PTSD) are among the most prevalent comorbid mental disorders in youth addiction treatment. Hence, screening for these internalizing disorders should be part of the standard routine at intake in substance use disorder treatment. We investigated the usefulness of the Depression, Anxiety and Stress Scale (DASS-21) as a screener for this purpose. METHODS: A nationally representative sample of 421 treatment-seeking youths aged 16-22 years with a primary cannabis, alcohol, cocaine, or amphetamine use disorder participated in the study. At intake, we administered the DASS-21 and the Mini International Neuropsychiatric Interview (MINI; Sheehan et al., 1998) based on the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5), as "gold standard," as part of a broader baseline assessment of the Youth in transition study [Moska et al. BMC Psychiatry. 2021;21(1):1-11]. RESULTS: At comparable sensitivity (0.80-0.84), based on the optimal cut-off value, specificity was higher for the DASS-21 total score detecting any DSM-5 internalizing disorder (0.62) than for the DASS subscales specifically detecting depression, anxiety, or PTSD (0.44, 0.49, and 0.51, respectively). Receiver operating characteristic curve analyses showed an area under the curve (AUC) value of 0.80 for the DASS total score to detect any internalizing disorder ("good discrimination"), compared with AUC values of 0.70-0.75 of the DASS depression and anxiety subscales to detect DSM-5 depression, anxiety, and PTSD ("fair discrimination"). The optimal DASS total score cut-off value of ≥44 for detecting any internalizing disorder resulted in 0.81 sensitivity, 0.62 specificity, 0.80 positive predictive value, and 0.64 negative predictive value. CONCLUSION: Given the high prevalence of comorbid internalizing disorders in youth addiction care, the need to address these comorbid disorders in treatment, and the favorable accuracy of the DASS to detect these disorders, we recommend to implement the DASS-21 as routine screener in youth addiction treatment in the Netherlands.

Schema therapy for patients with borderline personality disorder and comorbid alcohol dependence: A multiple-baseline case series design study.

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.

Advances in problematic usage of the internet research - A narrative review by experts from the European network for problematic usage of the internet.

Global concern about problematic usage of the internet (PUI), and its public health and societal costs, continues to grow, sharpened in focus under the privations of the COVID-19 pandemic. This narrative review reports the expert opinions of members of the largest international network of researchers on PUI in the framework of the European Cooperation in Science and Technology (COST) Action (CA 16207), on the scientific progress made and the critical knowledge gaps remaining to be filled as the term of the Action reaches its conclusion. A key advance has been achieving consensus on the clinical definition of various forms of PUI. Based on the overarching public health principles of protecting individuals and the public from harm and promoting the highest attainable standard of health, the World Health Organisation has introduced several new structured diagnoses into the ICD-11, including gambling disorder, gaming disorder, compulsive sexual behaviour disorder, and other unspecified or specified disorders due to addictive behaviours, alongside naming online activity as a diagnostic specifier. These definitions provide for the first time a sound platform for developing systematic networked research into various forms of PUI at global scale. Progress has also been made in areas such as refining and simplifying some of the available assessment instruments, clarifying the underpinning brain-based and social determinants, and building more empirically based etiological models, as a basis for therapeutic intervention, alongside public engagement initiatives. However, important gaps in our knowledge remain to be tackled. Principal among these include a better understanding of the course and evolution of the PUI-related problems, across different age groups, genders and other specific vulnerable groups, reliable methods for early identification of individuals at risk (before PUI becomes disordered), efficacious preventative and therapeutic interventions and ethical health and social policy changes that adequately safeguard human digital rights. The paper concludes with recommendations for achievable research goals, based on longitudinal analysis of a large multinational cohort co-designed with public stakeholders.

Digital Interventions for People With Co-Occurring Depression and Problematic Alcohol Use: A Systematic Review and Meta-Analysis.

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.

The relationship between craving and insular morphometry in regular cocaine users: Does sex matter?

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.

Identifying Subgroups of Cannabis Users Based on Help-Seeking Preferences: A Latent Class Analysis.

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.

Metacognition and the effect of incentive motivation in two compulsive disorders: Gambling disorder and obsessive-compulsive disorder.

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.

Baseline severity and the prediction of placebo response in clinical trials for alcohol dependence: A meta-regression analysis to develop an enrichment strategy.

BACKGROUND: There is considerable unexplained variability in alcohol abstinence rates (AR) in the placebo groups of randomized controlled trials (RCTs) for alcohol dependence (AD). This is of particular interest because placebo responses correlate negatively with treatment effect size. Recent evidence suggests that the placebo response is lower in very heavy drinkers who show no "spontaneous improvement" prior to treatment initiation (high-severity population) than in a mild-severity population and in studies with longer treatment duration. We systematically investigated the relationship between population severity, treatment duration, and the placebo response in AR to inform a strategy aimed at reducing the placebo response and thereby increasing assay sensitivity in RCTs for AD. METHODS: We conducted a systematic literature review on placebo-controlled RCTs for AD.We assigned retained RCTs to high- or mild-severity groups of studies based on baseline drinking risk levels and abstinence duration before treatment initiation. We tested the effects of population severity and treatment duration on the placebo response in AR using meta-regression analysis. RESULTS: Among the 19 retained RCTs (comprising 1996 placebo-treated patients), 11 trials were high-severity and 8 were mild-severity RCTs. The between-study variability in AR was lower in the high-severity than in the mild-severity studies (interquartile range: 7.4% vs. 20.9%). The AR in placebo groups was dependent on population severity (p = 0.004) and treatment duration (p = 0.017) and was lower in the high-severity studies (16.8% at 3 months) than the mild-severity studies (36.7% at 3 months). CONCLUSIONS: Pharmacological RCTs for AD should select high-severity patients to decrease the magnitude and variability in the placebo effect and and improve the efficiency of drug development efforts for AD.

Treating posttraumatic stress disorder in substance use disorder patients with co-occurring posttraumatic stress disorder: study protocol for a randomized controlled trial to compare the effectiveness of different types and timings of treatment.

BACKGROUND: Posttraumatic stress disorder (PTSD) and substance use disorder (SUD) have high comorbidity. Although prior research indicated that PTSD can effectively be treated with Prolonged Exposure (PE) in these patients, reported effects are small and treatment dropout rates high. Eye Movement Desensitization and Reprocessing (EMDR) and Imagery Rescripting (ImRs) are other promising treatment options for PTSD, that have not yet been examined in this patient group. Furthermore, it is unclear whether PTSD treatment is most effective when offered simultaneous to or after SUD treatment. METHODS: In this article, the Treatment Of PTSD and Addiction (TOPA) study is described: a Dutch randomized controlled trial (RCT) that studies the effectiveness of PTSD treatment as an add-on to regular SUD treatment in patients with SUD and co-occurring PTSD. Effects of PE, EMDR, ImRs, and a 3-month SUD treatment only condition will be compared, as well as simultaneous SUD/PTSD treatment to sequential SUD/PTSD treatment. The primary outcome measure is PTSD symptoms. Secondary outcomes are: treatment completion, psychological distress, substance use, interpersonal problems, emotion dysregulation, and trauma-related emotions guilt, shame, and anger. DISCUSSION: This study is the first to compare effects of PE, EMDR, and ImRs in one study and to compare simultaneous SUD/PTSD treatment to sequential SUD/PTSD treatment as well. This RCT will provide more knowledge about the effectiveness of different treatment strategies for PTSD in patients with co-occurring SUD and will ultimately improve treatment outcomes for patients with this common co-morbidity worldwide. TRIAL REGISTRATION: Netherlands Trial Register (NTR), Identifier: NL7885 . Registered 22 July 2019.

Effectiveness of a digital alcohol moderation intervention as an add-on to depression treatment for young adults: study protocol of a multicentre pragmatic randomized controlled trial.

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 ).

Youth in transition: Study protocol of a prospective cohort study into the long-term course of addiction, mental health problems and social functioning in youth entering addiction treatment.

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.

Alcohol Reduction to Reduce Relapse in Acute Alcoholic Pancreatitis-Missed Opportunities.

AIM: Resuming drinking is a main contributant to recurrence in alcoholic pancreatitis. We assessed current clinical practice in the Netherlands regarding alcohol in managing patients with a first episode of acute alcoholic pancreatitis. METHODS: A survey was distributed to 35 hospitals affiliated with the Dutch Pancreatitis Study Group. We evaluated current support based on various components of brief interventions, the participation of psychosocial healthcare providers, the cooperation with the primary care physicians and the presence of a protocol and its implementation. RESULTS: The response rate was 100% (n = 35). Psychoeducation is the most frequently performed intervention in current support treatment (97% of hospitals). In 17% of hospitals, healthcare providers with a psychosocial background routinely participate in current support treatment; 37% of hospitals create an individual treatment plan in which goals regarding alcohol cessation are specified and only 46% of hospitals provide the primary care physician with specific discharge information; 31% of hospitals indicate that the treatment is uniformly performed within their division of Gastroenterology. Protocols are available in 3% of the hospitals surveyed. Opportunities to involve the patient's social network were not given sufficient priority. CONCLUSION: Among Dutch hospitals, there is no routine management strategy with regard to enhancing treatment for heavy alcohol use in alcoholic pancreatitis patients. There is a need to test a validated support program in randomized studies. Meanwhile, possible opportunities for effecting change are often missed.

Mapping cortical and subcortical asymmetries in substance dependence: Findings from the ENIGMA Addiction Working Group.

Brain asymmetry reflects left-right hemispheric differentiation, which is a quantitative brain phenotype that develops with age and can vary with psychiatric diagnoses. Previous studies have shown that substance dependence is associated with altered brain structure and function. However, it is unknown whether structural brain asymmetries are different in individuals with substance dependence compared with nondependent participants. Here, a mega-analysis was performed using a collection of 22 structural brain MRI datasets from the ENIGMA Addiction Working Group. Structural asymmetries of cortical and subcortical regions were compared between individuals who were dependent on alcohol, nicotine, cocaine, methamphetamine, or cannabis (n = 1,796) and nondependent participants (n = 996). Substance-general and substance-specific effects on structural asymmetry were examined using separate models. We found that substance dependence was significantly associated with differences in volume asymmetry of the nucleus accumbens (NAcc; less rightward; Cohen's d = 0.15). This effect was driven by differences from controls in individuals with alcohol dependence (less rightward; Cohen's d = 0.10) and nicotine dependence (less rightward; Cohen's d = 0.11). These findings suggest that disrupted structural asymmetry in the NAcc may be a characteristic of substance dependence.

Effects of Multiple Detoxifications on Withdrawal Symptoms, Psychiatric Distress and Alcohol-Craving in Patients with an Alcohol Use Disorder.

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: <2 previous detoxifications and ≥2 previous detoxifications. Patients completed the Dutch version of the Severity of Withdrawal Scale (SWS), Depression Anxiety Stress Scales (DASS-21), VAS Craving, and Desires for Alcohol Questionnaire (DAQ). Linear mixed effects models were applied, controlling for the number of drinks consumed in the past 30 days and alcohol drinking history (years). Patients who had undergone ≥2 detoxifications reported statistically significantly higher scores on SWS withdrawal and DASS psychiatric symptoms. Also, craving patterns were different between groups, as shown by a statistically significant interaction effect for VAS craving for the time of day factor (morning vs. evening). No statistically significant group differences were found for DAQ scores and post-detoxification drinking outcomes. Due to relatively low 1-month follow-up rates our power was limited to detect such a difference. The present study contributes to the existing body of evidence that multiple detoxifications are associated with aggravated withdrawal/psychiatric pathology, and distinct diurnal patterns of VAS craving. Several clinical implications are discussed and alternative strategies are provided to manage repeated cycles of detoxifications.