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.

Types of childhood maltreatment as predictors of posttraumatic stress disorder severity and complex posttraumatic stress disorder in patients with substance use disorders.

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.

All types of Childhood Maltreatment are associated with PTSD severity.Emotional Abuse and Sexual Abuse are most predictive for PTSD severity.Emotional Abuse is most predictive for CPTSD classification and symptom severity.

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.

Association between endocrine and neuropsychological endophenotypes and gambling disorder severity.

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.

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.

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.

Preferences of young adults on the development of a new digital add-on alcohol intervention for depression treatment: A qualitative study.

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.

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.

Temporal order of diagnosis between gambling disorder and substance use disorders: Longitudinal results from the Norwegian Patient Registry.

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.

A guided digital intervention to reduce cannabis use: The ICan randomized controlled trial.

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 dbetween = 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 dbetween = 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.

Striatal ups or downs? Neural correlates of monetary reward anticipation, cue reactivity and their interaction in alcohol use disorder and gambling disorder.

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.

Exploring the effects of a wearable biocueing app (Sense-IT) as an addition to aggression regulation therapy in forensic psychiatric outpatients.

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.

Forensic Psychiatric Outpatients' and Therapists' Perspectives on a Wearable Biocueing App (Sense-IT) as an Addition to Aggression Regulation Therapy: Qualitative Focus Group and Interview Study.

BACKGROUND: Given the increased use of smart devices and the advantages of individual behavioral monitoring and assessment over time, wearable sensor-based mobile health apps are expected to become an important part of future (forensic) mental health care. For successful implementation in clinical practice, consideration of barriers and facilitators is of utmost importance. OBJECTIVE: The aim of this study was to provide insight into the perspectives of both psychiatric outpatients and therapists in a forensic setting on the use and implementation of the Sense-IT biocueing app in aggression regulation therapy. METHODS: A combination of qualitative methods was used. First, we assessed the perspectives of forensic outpatients on the use of the Sense-IT biocueing app using semistructured interviews. Next, 2 focus groups with forensic therapists were conducted to gain a more in-depth understanding of their perspectives on facilitators of and barriers to implementation. RESULTS: Forensic outpatients (n=21) and therapists (n=15) showed a primarily positive attitude toward the addition of the biocueing intervention to therapy, with increased interoceptive and emotional awareness as the most frequently mentioned advantage in both groups. In the semistructured interviews, patients mainly reported barriers related to technical or innovation problems (ie, connection and notification issues, perceived inaccuracy of the feedback, and limitations in the ability to personalize settings). In the focus groups with therapists, 92 facilitator and barrier codes were identified and categorized into technical or innovation level (n=13, 14%), individual therapist level (n=28, 30%), individual patient level (n=33, 36%), and environmental and organizational level (n=18, 20%). The predominant barriers were limitations in usability of the app, patients' motivation, and both therapists' and patients' knowledge and skills. Integration into treatment, expertise within the therapists' team, and provision of time and materials were identified as facilitators. CONCLUSIONS: The chances of successful implementation and continued use of sensor-based mobile health interventions such as the Sense-IT biocueing app can be increased by considering the barriers and facilitators from patients' and therapists' perspectives. Technical or innovation-related barriers such as usability issues should be addressed first. At the therapist level, increasing integration into daily routines and enhancing affinity with the intervention are highly recommended for successful implementation. Future research is expected to be focused on further development and personalization of biocueing interventions considering what works for whom at what time in line with the trend toward personalizing treatment interventions in mental health care.

Alcohol use as a predictor of the course of major depressive disorder: a prospective population-based study.

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

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.

Goal-directed and habitual decision making under stress in gambling disorder: An fMRI study.

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.

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.

Effects of 10 add-on HF-rTMS treatment sessions on alcohol use and craving among detoxified inpatients with alcohol use disorder: a randomized sham-controlled clinical trial.

BACKGROUND AND AIMS: Alcohol use disorder (AUD) is a chronic disorder with high relapse rates. There are currently few clinical trials of high frequency repetitive transcranial magnetic stimulation (HF-rTMS) to reduce alcohol use among AUD patients, and results are mixed. The current study tested the effect of 10 add-on sessions of HF-rTMS over the right dorsolateral pre-frontal cortex (DLPFC) on alcohol use and craving. DESIGN: Single-center, single blind sham-controlled parallel-group RCT (n = 80), with 3 and 6 months follow-up. SETTING: Clinical treatment center in Amsterdam, the Netherlands. PARTICIPANTS: Eighty detoxified and abstinent AUD inpatients in clinical treatment (20 females, average age = 44.35 years). INTERVENTION: Ten sessions of active or sham HF-rTMS (60 10 Hz trains of 5 sec at 110% motor threshold) over the right DLPFC on 10 consecutive work-days. MEASUREMENTS: The primary outcome measure is the number of abstinent days over 6-month follow-up (FU). Secondary outcome measures are craving over 6-month FU (alcohol urge questionnaire and obsessive-compulsive drinking scale), time to first relapse over 6-month FU and grams of alcohol consumed over 6-month FU. Additional outcome measures: full abstinence over 6-month FU and treatment success over 12-month FU. FINDINGS: HF-rTMS did not affect the number of abstinent days over 6 months FU [sham = 124 ± 65.9 days, active = 115 ± 69.8 days, difference: 9 days, 95% confidence interval (CI) = Poisson model: 0.578-3.547]. Moreover, HF-rTMS did not affect craving (AUQ/OCDS) (sham = 15.38/5.28, active = 17.48/4.75, differences = 2.1/-0.53, 95% CI mixed-effects model = -9.14 to 2.07/-1.44 to 2.40). CONCLUSIONS: There was no clear evidence that high-frequency repetitive transcranial magnetic stimulation over the right dorsolateral pre-frontal cortex treatment has a long-term positive effect on alcohol use or craving as add-on treatment for alcohol use disorder. High treatment response at 6-month follow-up could have limited the possibility to find an effect.

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.

Recalibrating single-study effect sizes using hierarchical Bayesian models.

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.