The Comprehensive Adversity Measure (CAM): A measure of early adversity and its severity.

BACKGROUND: Early adversity scales often display insufficient content coverage and typically assess the presence of adversity, but not its severity. OBJECTIVE: To address some of these limitations, we developed the 13-item Youth and Childhood Adversity Scale. We subsequently revised and expanded the scale regarding content coverage and item wording, resulting in a 22-item version, which we here describe. METHODS: We conducted one cross-sectional (N = 1498; 43.9 % females; 24.42 years, SD = 3.72, range: 18-30 years) and one longitudinal study (N = 1084; 39.6 % females; 32 years, SD = 10.49, range: 18-75 years). To reflect the nature of the revised measure more accurately, it was named the Comprehensive Adversity Measure (CAM). RESULTS: Exploratory factor analysis suggested a one-factor model for both the presence/absence and the severity facet, which both displayed good model fit in subsequent confirmatory factor analyses. Factor models demonstrated at least scalar measurement invariance across gender and country (US/UK). Correlations with psychological distress, depression, anxiety, substance use, posttraumatic stress symptoms, obsessive-compulsive symptoms, suicide attempts, rumination, social comparison, self-esteem, and quality of life provided evidence in support of construct validity - concurrently and prospectively. CONCLUSIONS: The CAM offers a psychometrically-sound, content-wise comprehensive, and free to use assessment of early adversity.

Similarities and differences in the functions of non-suicidal self-injury (NSSI) across gender non-conforming and cisgender young adults.

BACKGROUND: Non-suicidal self-injury (NSSI) can be motivated by a broad range of functions and many individuals report multiple reasons for self-injuring. Most NSSI research has involved predominantly female samples and few studies have examined gender similarities and differences in function endorsement. METHODS: We characterise the prevalence and versatility of NSSI functions within a gender-diverse online sample of cisgender women (cis-women; n = 280), cisgender men (cis-men; n = 176), and transgender, non-binary, and other gender non-conforming young adults (TGNC; n = 80) age 18-30 (M = 23.73, SD = 3.55). The Ottawa Self-Injury Inventory (OSI-F) assessed 24 intrapersonal and social functions across nine domains: affect regulation, self-punishment, anti-dissociation, anti-suicide, sensation seeking, sexuality, interpersonal influence, and body image. RESULTS: TGNC participants and cis-women were significantly more likely to report intrapersonally motivated NSSI and greater function versatility than cis-men. Low mood, emotional distress, suicidality, and trauma symptomology appeared to contribute to gender differences in function endorsement. Gender similarities also emerged; across groups, intrapersonal functions were substantially more common than social functions, and the most endorsed domains were affect regulation and self-punishment. No domains were gender specific. LIMITATIONS: The OSI-F was developed from majority female samples and may not adequately capture the experiences of other gender groups. CONCLUSIONS: Interventions which reduce distress and strengthen emotion regulation are likely to benefit individuals who self-injure regardless of gender. However, most individuals report multiple NSSI functions and person-centred interventions which address this complexity are needed. Future research should develop gender-informed treatment models which consider the unique experiences of TGNC individuals and cis-men who self-injure.

A comprehensive evaluation of the neurocognitive predictors of problematic alcohol use, eating, pornography, and internet use: A 6-month longitudinal study.

Background and aims: Cognitive control and reward-related abnormalities are centrally implicated in addiction. However, findings from longitudinal studies addressing neurocognitive predictors of addictive behaviors are mixed. Further, little work has been conducted predicting non-substance-related addictive behaviors. Our study aimed to assess predictors of substance and non-substance addictive behaviors in a community sample, systematically evaluating each neurocognitive function's independent influence on addictive behavior. Methods: Australians (N = 294; 51.7% female; M[SD] age = 24.8[4.7] years) completed online neurocognitive tasks and surveys at baseline and 3-month follow-up. Self-report scales assessed problematic alcohol use, addictive eating (AE), problematic pornography use (PPU), and problematic internet use (PUI) at 3- and 6-month follow-ups. Linear regressions with bootstrapping assessed neurocognitive predictors for each addictive behavior across a 6-month period. Results: Neurocognition at baseline did not predict AE or PUI severity at 6-month follow-up. Less delay discounting at baseline predicted higher PPU at 6-month follow-up (ß = -0.16, p = 0.005). Poorer performance monitoring at baseline predicted higher AE at 3-month follow-up (ß = -0.16, p = 0.004), and more reward-related attentional capture at 3-months predicted higher AE at 6-month follow-up (ß = 0.14, p = 0.033). Less reward-related attentional capture (ß = -0.14, p = 0.003) and less risk-taking under ambiguity (ß = -0.11, p = 0.029) at baseline predicted higher PUI at 3-month follow-up. All findings were of small effect size. None of the neurocognitive variables predicted problematic alcohol use. Discussion and conclusions: We were unable to identify a core set of specific neurocognitive functions that reliably predict multiple addictive behavior types. However, our findings indicate both cognitive control and reward-related functions predict non-substance addictive behaviors in different ways. Findings suggest that there may be partially distinct neurocognitive mechanisms contributing to addiction depending on the specific addictive behavior.

A familial subtype of gambling disorder.

Background: Although family history of psychiatric disorders has often been considered potentially useful in understanding clinical presentations in patients, it is less clear what a positive gambling family history means for people with gambling disorder. We sought to understand the clinical impact of having a first-degree relative with gambling disorder in a sample of adults with gambling disorder. Methods: Data from 455 participants (aged 18-65 years) who had participated in previous pharmacological and psychotherapeutic clinical trials for gambling disorder were pooled in a secondary analysis. Demographic and clinical variables were compared between those who did versus did not have one or more first-degree relative(s) with gambling disorder. Additionally, we examined whether a family history of gambling disorder was associated with treatment outcome. Results: 223 (49.0%) participants had at least one first-degree family member(s) with gambling disorder. In terms of clinical variables, family history of gambling disorder was significantly associated with being female, having an earlier age of gambling onset, longer duration of untreated gambling illness, a greater likelihood of developing legal problems secondary to gambling, and higher rates of alcohol use disorder in family members. Family history of gambling disorder was also associated with a greater gambling symptom improvement from pharmacotherapy. Conclusions: These results indicate that gamblers with a first-degree family member with a gambling disorder may have a unique clinical presentation and better response to treatment interventions.

Comorbid Posttraumatic Stress Disorder and Trichotillomania.

Objective: To examine rates of current posttraumatic stress disorder (PTSD) in adults with trichotillomania and further assess how PTSD impacts symptom severity and functionality.Methods: 209 adults with trichotillomania completed a self-report form for PTSD. The survey was open between April 10, 2023, and May 11, 2023. Independent sample t-tests and Pearson χ2 tests were used to analyze differences in symptom severity and comorbidity presence between participants with and without co-occurring PTSD.Results: Forty (19.1%) individuals with trichotillomania endorsed symptoms consistent with current PTSD. Participants with PTSD were significantly more likely to be male, to have a co-occurring alcohol use disorder, and to engage in various impulsive behaviors (gambling, sex, stealing, and eating). There were no significant associations between PTSD status and trichotillomania symptom severity.Conclusion: PTSD is frequently comorbid with trichotillomania, and their co occurrence enhances the risk for a range of impulsive behaviors. Future research should examine whether treating the core trauma in a subset of people with trichotillomania may address a range of co-occurring disorders.Prim Care Companion CNS Disord 2024;26(4):24m03751. Author affiliations are listed at the end of this article.

Validation of an abbreviated Big Five personality inventory at large population scale: Psychometric structure and associations with common psychiatric and neurological disorders.

BACKGROUND: The five-factor model of personality, as quantified using instruments such as the Big Five Inventory, consists of broad personality domains including Extraversion, Agreeableness, Conscientiousness, Neuroticism (emotional instability), and Openness. Such instruments typically include >40 items. However, instruments with many items can be unwieldly and a cause of measurement error in clinical and cohort studies where multiple scales are sequenced. Conversely, established 5- and 10-item versions of the Big Five Inventory have poor reliability. Here, we developed and validated an abbreviated 18-item Big Five Inventory that balances efficiency, reliability and sensitivity. METHOD: We analysed three datasets (N = 59,797, N = 21,177, and N = 87,983) from individuals who participated in the online Great British Intelligence Test (GBIT) study, a collaborative citizen science project with BBC2 Horizon. We applied factor analyses (FA), predictive normative modelling, and one-sample t-tests to validate the 18-item version of the Big Five and to investigate its associations with psychiatric and neurological conditions. RESULTS: The 18-item version of the Big Five Inventory had higher validity and retest reliability compared to the other previously shortened versions in the literature, with comparable demographic associations to the full Big Five Inventory. It exhibited strong (i.e. large effect size) associations with psychiatric conditions, and moderate (small-medium) associations with neurological conditions. Neuroticism (emotional instability) was substantially higher in all psychiatric conditions, whereas Conscientiousness, Openness and Extraversion showed differential associations across conditions. CONCLUSION: The newly validated 18-item version of the Big Five provides a convenient means of measuring personality traits that is suitable for deployment in a range of studies. It retains psychometric structure, retest reliability and clinical-group sensitivity, as compared to the full original scale.

Sleep Problems and Gambling Disorder: Cross-Sectional Relationships in a Young Cohort.

AIMS: To investigate the potential association between gambling disorder and symptoms of sleep problems (including insomnia and excessive daytime sleepiness). It was hypothesised that, compared to controls, individuals with gambling disorder would have significantly greater disturbance of sleep, as indicated by increased scores in: (1) sleep items on the Hamilton Anxiety Rating Scale (HAM-A) and Hamilton Rating Scale for Depression (HAM-D); (2) total score on the HAM-A and HAM-D; and (3) the Epworth Sleepiness Scale (ESS). METHODS: Secondary analysis of previously published data from 152 young adults, aged 18-29 years. Individuals were stratified into three groups: controls, those at risk of gambling disorder, and those with gambling disorder. One-way ANOVAs with post-hoc tests were conducted to determine whether groups differed significantly in sleep item scores and total scores of the HAM-A and HAM-D, and the ESS. RESULTS: HAM-D scale insomnia item scores were significantly higher in the disorder group, when compared to controls, this being particularly marked for middle and late insomnia. The HAM-A item score indicated significantly worse sleep quality in the disorder group, compared to at risk and control groups. Total HAM-A and HAM-D scores were significantly higher in the disorder group, but ESS scores did not differ significantly. CONCLUSION: Measures of disruptions in sleep were significantly higher in gambling disorder than controls. Anxiety and depressive symptom severity was also significantly higher in the gambling disorder group. Further research could have implications for identification and treatment of sleep disorders and psychiatric comorbidities in gambling disorder.

Lifetime alcohol use disorder and gambling disorder: clinical profile and treatment response.

OBJECTIVES: Gambling disorder affects 0.5-2.4% of the population and shows strong associations with lifetime alcohol use disorder. Very little is known regarding whether lifetime alcohol use disorder can impact the clinical presentation or outcome trajectory of gambling disorder. METHODS: Data were pooled from previous clinical trials conducted on people with gambling disorder, none of whom had current alcohol use disorder. Demographic and clinical variables were compared between those who did versus did not have lifetime alcohol use disorder. RESULTS: Of the 621 participants in the clinical trials, 103 (16.6%) had a lifetime history of alcohol use disorder. History of alcohol use disorder was significantly associated with male gender (relative risk [RR] = 1.42), greater body weight (Cohen's D = 0.27), family history of alcohol use disorder in first-degree relative(s) (RR = 1.46), occurrence of previous hospitalization due to psychiatric illness (RR = 2.68), and higher gambling-related legal problems (RR = 1.50). History of alcohol use disorder was not significantly associated with other variables that were examined, such as severity of gambling disorder or extent of functional disability. Lifetime alcohol use disorder was not significantly associated with the extent of clinical improvement in gambling disorder symptoms during the subsequent clinical trials. CONCLUSIONS: These data highlight that lifetime alcohol use disorder is an important clinical variable to be considered when assessing gambling disorder because it is associated with several untoward features (especially gambling-related legal problems and prior psychiatric hospitalization). The study design enabled these associations to be disambiguated from current or recent alcohol use disorder.

Non-suicidal self-injury in trichotillomania and skin picking disorder.

BACKGROUND: Trichotillomania and skin picking disorder have been characterized as body-focused repetitive behavior (BFRB) disorders (i.e., repetitive self-grooming behaviors that involve biting, pulling, picking, or scraping one's own hair, skin, lips, cheeks, or nails). Trichotillomania and skin picking disorder have also historically been classified, by some, as types of compulsive self-injury as they involve repetitive hair pulling and skin picking, respectively. The question of the relationship of these disorders to more conventional forms of self-injury such as cutting or self-burning remains incompletely investigated. The objective of this study was to examine the relationship of these two disorders with non-suicidal self-injury (NSSI). METHODS: Adults with trichotillomania (n = 93) and skin picking (n = 105) or both (n = 82) were recruited from the general population using advertisements and online support groups and completed an online survey. Participants completed self-report instruments to characterize clinical profiles and associated characteristics. In addition, each participant completed a mental health history questionnaire. RESULTS: Of the 280 adults with BFRB disorders, 141 (50.1%) reported a history of self-injury independent of hair pulling and skin picking. Participants with a history of self-injury reported significantly worse pulling and picking symptoms (p < .001) and were significantly more likely to have co-occurring alcohol problems (p < .001), borderline personality disorder (p < .001), buying disorder (p < .001), gambling disorder (p < .001), compulsive sex behavior (p < 001), and binge eating disorder (p = .041). CONCLUSIONS: NSSI appears common in trichotillomania and skin picking disorder and may be part of a larger constellation of behaviors associated with impulse control or reward-related dysfunction.

Emotion regulation across psychiatric disorders.

OBJECTIVE: Difficulties with emotion regulation have been associated with multiple psychiatric conditions. In this study, we aimed to investigate emotional regulation difficulties in young adults who gamble at least occasionally (ie, an enriched sample), and diagnosed with a range of psychiatric disorders using the validated Difficulties in Emotion Regulation Scale (DERS). METHODS: A total of 543 non-treatment-seeking individuals who had engaged in gambling activities on at least 5 occasions within the previous year, aged 18-29 were recruited from general community settings. Diagnostic assessments included the Mini International Neuropsychiatric Inventory, Minnesota Impulsive Disorders Interview, attention-deficit/hyperactivity disorder World Health Organization Screening Tool Part A, and the Structured Clinical Interview for Gambling Disorder. Emotional dysregulation was evaluated using DERS. The profile of emotional dysregulation across disorders was characterized using Z-scores (those with the index disorder vs. those without the index disorder). RESULTS: Individuals with probable ADHD displayed the highest level of difficulties in emotional regulation, followed by intermittent explosive disorder, social phobia, and generalized anxiety disorder. In contrast, participants diagnosed with obsessive-compulsive disorder showed relatively lower levels of difficulties with emotional regulation. CONCLUSIONS: This study highlights the importance of recognizing emotional dysregulation as a trans-diagnostic phenomenon across psychiatric disorders. The results also reveal differing levels of emotional dysregulation across diagnoses, with potential implications for tailored treatment approaches. Despite limitations such as small sample sizes for certain disorders and limited age range, this study contributes to a broader understanding of emotional regulation's role in psychiatric conditions.

Examining the unique relationships between problematic use of the internet and impulsive and compulsive tendencies: network approach.

BACKGROUND: Both impulsivity and compulsivity have been identified as risk factors for problematic use of the internet (PUI). Yet little is known about the relationship between impulsivity, compulsivity and individual PUI symptoms, limiting a more precise understanding of mechanisms underlying PUI. AIMS: The current study is the first to use network analysis to (a) examine the unique association among impulsivity, compulsivity and PUI symptoms, and (b) identify the most influential drivers in relation to the PUI symptom community. METHOD: We estimated a Gaussian graphical model consisting of five facets of impulsivity, compulsivity and individual PUI symptoms among 370 Australian adults (51.1% female, mean age = 29.8, s.d. = 11.1). Network structure and bridge expected influence were examined to elucidate differential associations among impulsivity, compulsivity and PUI symptoms, as well as identify influential nodes bridging impulsivity, compulsivity and PUI symptoms. RESULTS: Results revealed that four facets of impulsivity (i.e. negative urgency, positive urgency, lack of premeditation and lack of perseverance) and compulsivity were related to different PUI symptoms. Further, compulsivity and negative urgency were the most influential nodes in relation to the PUI symptom community due to their highest bridge expected influence. CONCLUSIONS: The current findings delineate distinct relationships across impulsivity, compulsivity and PUI, which offer insights into potential mechanistic pathways and targets for future interventions in this space. To realise this potential, future studies are needed to replicate the identified network structure in different populations and determine the directionality of the relationships among impulsivity, compulsivity and PUI symptoms.

Linking Striatal Dopaminergic Asymmetry with Personality Traits: Insights from Gambling Disorder.

The role of dopamine in the pathophysiology of gambling disorder (GD) remains incompletely understood, with disparate research findings concerning presynaptic and postsynaptic structures and dopaminergic synthesis. The aim of this study was to investigate potential correlations between striatal dopamine transporter (DAT) lateralization and asymmetry index, as assessed by 123I-FP-CIT SPECT, and temperamental traits, as measured by Cloninger's Temperament and Character Inventory (TCI), in GD subjects. Significant associations were found between DAT binding asymmetries in the caudate and putamen and the temperamental dimensions of harm avoidance and novelty seeking. Specifically, high novelty seeking scores correlated with increased DAT binding in the left caudate relative to the right, whereas higher harm avoidance scores corresponded to increased DAT binding in the right putamen relative to the left. These observations potentially imply that the asymmetry in DAT expression in the basal ganglia could be an outcome of hemispheric asymmetry in emotional processing and behavioural guidance. In summary, our study provides evidence supporting the relationship between DAT asymmetries, temperamental dimensions and GD. Future investigations could be directed towards examining postsynaptic receptors to gain a more comprehensive understanding of dopamine's influence within the basal ganglia circuit in disordered gambling. If confirmed in larger cohorts, these findings could have substantial implications for the tailoring of individualized neuromodulation therapies in the treatment of behavioural addictions.

Increased apathy post-interstitial laser capsulotomy for refractory obsessive-compulsive disorder.

BACKGROUND: MRI guided laser interstitial thermal therapy (M-LITT) capsulotomy has proven to be efficacious in decreasing refractory obsessive-compulsive disorder (OCD) related symptomatology yet capsulotomy either via radiosurgery or radiofrequency ablation has in some patients led to increased apathy following surgery. The current case series aims to investigate objective patient-reported change in apathy, disinhibition, depression, and executive dysfunction following anterior capsulotomy via M-LITT for OCD. METHODS: Ten consecutive patients pre- and post-M-LITT completed measures of OCD, apathy, disinhibition, executive dysfunction, and depression (Mtime between = 1.3 years; 0.42-3.7 years). Reliable Change Index (RCI) was used to evaluate change in pre- and post-M-LITT. OCD symptom response was evaluated using percent change (Y-BOCS scores: 24-34 % reduction indicating partial response; ≥35% reduction indicating full response). RESULTS: Positive post-surgical change was noted in OCD symptomatology with >65% reporting a partial or full response. However, six patients endorsed increased apathy with half of the non-responders (e.g., less than <24% score reduction on Y-BOCS) reporting increases in apathy. Patients reported relatively stable disinhibition and executive dysfunction, while over half reported a decrease in depression symptoms. Two of the non-responders and one responder endorsed increased apathy despite stable or improved depression symptoms, disinhibition, and executive dysfunction. CONCLUSIONS: Most patients in the current cohort achieved full-or-partial OCD recovery. Yet, 60% of patients also reported significant increases in apathy, despite experiencing a decrease in depression symptoms, with stable disinhibition and executive dysfunction. Despite these promising improvements in OCD symptomatology following M-LITT, further investigations of the impact of surgery and lesion location on apathy levels is clearly warranted using objective, quantifiable methods.

The Role of Axillary Lymph Node Dissection versus Sentinel Lymph Node Dissection in Breast Cancer Patients with Clinical N2b-N3c Disease Who Receive Adjuvant Radiotherapy.

BACKGROUND: For breast cancer with advanced regional lymph node involvement, axillary lymph node dissection (ALND) remains the standard of care for staging and treating the axilla despite the presence of undissected lymph nodes. The benefit of ALND in this setting is unknown. OBJECTIVES: We sought to describe national patterns of care of axillary surgery and its association with overall survival (OS) among women with cN2b-N3c breast cancer who receive adjuvant radiotherapy. PATIENTS AND METHODS: We identified female patients with cN2b-N3c breast cancer from 2012 to 2017 from the National Cancer Database. Clinical and demographic information were analyzed using Wilcoxon rank sum and χ2 tests. Predictors of receipt of ALND and predictors of death were identified with multivariable logistic regression modeling. Inverse probability of treatment weighting was implemented to adjust for differences in treatment cohorts. The Kaplan-Meier method was used to evaluate OS. RESULTS: We identified 7167 patients. Of these, 922 (13%) received SLNB and 6254 (87%) received ALND; 7% were cN2b, 19% cN3a, 24% cN3b, 19% cN3c, and 31% cN3, not otherwise specified. Predictors of receipt of ALND were age 50-69 years [odds ratio (OR) 1.3, p < 0.01], cN3a (OR 7.6, p < 0.01), cN3b (OR 2.8, p < 0.01), and cN3c (OR 4.2, p < 0.01). Predictors of death included cN3c (OR 1.9, p < 0.01), age 70-90 years (OR 1.5, p = 0.01), and positive surgical margins (OR 1.5, p < 0.01). After cohort balancing, ALND was not associated with improved OS when compared with SLNB (HR 0.99, p = 0.91). CONCLUSIONS: ALND in patients with advanced nodal disease was not associated with improved survival compared with SLNB for women who receive adjuvant radiotherapy.

Treatment discontinuation in pharmacological clinical trials for gambling disorder.

BACKGROUND: Gambling disorder affects 0.5-2% of the population, and of those who receive treatment, dropout tends to be relatively high. Very little is known about participant-specific variables linked to treatment discontinuation/dropout in gambling disorder, especially in pharmacological clinical trial settings. METHODS: Data were pooled from eight previous randomized, controlled pharmacological clinical trials conducted in people with gambling disorder. Demographic and clinical variables were compared between those who did versus did not subsequently dropout from those treatment trials. RESULTS: The sample comprised data from 635 individuals, and the overall rate of treatment dropout was 40%. Subsequent treatment dropout was significantly associated with the following: positive family history of gambling disorder in one or more first degree relatives (relative risk [RR] of dropout in those with positive history vs not = 1.30), preference for mainly strategic vs non-strategic gambling activities (RR = 1.43), lower levels of education (Cohen's D = 0.22), and higher levels of functional disability (Cohen's D = 0.18). These variables did not differ significantly as a function of treatment condition (medication versus placebo). Dropouts and completers did not differ significantly in terms of the other demographic or clinical variables that were considered. CONCLUSIONS: This study identified several candidate participant-specific predictors of pharmacological treatment dropout in gambling disorder. The findings highlight the need for future studies to address a wider range of contextual variables at large scale (including also study-specific variables e.g. trial/intervention duration), including in naturalistic treatment and clinical trial settings, with a view to developing algorithms that might usefully predict dropout risk.

Cognition in trichotillomania: a meta-analysis.

OBJECTIVE: Trichotillomania (TTM) is a mental health disorder characterized by repetitive urges to pull out one's hair. Cognitive deficits have been reported in people with TTM compared to controls; however, the current literature is sparse and inconclusive about affected domains. We aimed to synthesize research on cognitive functioning in TTM and investigate which cognitive domains are impaired. METHODS: After preregistration on the International Prospective Register of Systematic Reviews (PROSPERO), we conducted a comprehensive literature search for papers examining cognition in people with TTM versus controls using validated tests. A total of 793 papers were screened using preestablished inclusion/exclusion criteria, yielding 15 eligible studies. Random-effects meta-analysis was conducted for 12 cognitive domains. RESULTS: Meta-analysis demonstrated significant deficits in motor inhibition and extradimensional (ED) shifting in people with TTM versus controls as measured by the stop-signal task (SST) (Hedge's g = 0.45, [CI: 0.14, 0.75], p = .004) and ED set-shift task (g = 0.38, [CI: 0.13, 0.62], p = .003), respectively. There were no significant between-group differences in the other cognitive domains tested: verbal learning, intradimensional (ID) shifting, road map spatial ability, pattern recognition, nonverbal memory, executive planning, spatial span length, Stroop inhibition, Wisconsin card sorting, and visuospatial functioning. Findings were not significantly moderated by study quality scores. CONCLUSIONS: Motor inhibition and ED set-shifting appear impaired in TTM. However, a cautious interpretation of results is necessary as samples were relatively small and frequently included comorbidities. Treatment interventions seeking to improve inhibitory control and cognitive flexibility merit exploration for TTM.

A systematic review of the cognitive effects of the COMT inhibitor, tolcapone, in adult humans.

OBJECTIVE: The catechol-o-methyltransferase (COMT) inhibitor tolcapone constitutes a potentially useful probe of frontal cortical dopaminergic function. The aim of this systematic review was to examine what is known of effects of tolcapone on human cognition in randomized controlled studies. METHODS: The study protocol was preregistered on the Open Science Framework. A systematic review was conducted using PubMed to identify relevant randomized controlled trials examining the effects of tolcapone on human cognition. Identified articles were then screened against inclusion and exclusion criteria. RESULTS: Of the 22 full-text papers identified, 13 randomized control trials were found to fit the pre-specified criteria. The most consistent finding was that tolcapone modulated working memory; however, the direction of effect appeared to be contingent on the COMT polymorphism (more consistent evidence of improvement in Val-Val participants). There were insufficient nature and number of studies for meta-analysis. CONCLUSION: The cognitive improvements identified upon tolcapone administration, in some studies, are likely to be due to the level of dopamine in the prefrontal cortex being shifted closer to its optimum, per an inverted U model of prefrontal function. However, the results should be interpreted cautiously due to the small numbers of studies. Given the centrality of cortical dopamine to understanding human cognition, studies using tolcapone in larger samples and across a broader set of cognitive domains would be valuable. It would also be useful to explore the effects of different dosing regimens (different doses; and single versus repeated administration).

Silymarin (Milk Thistle) Treatment of Adults With Gambling Disorder: A Double-Blind, Placebo-Controlled Trial.

OBJECTIVE: Data on the pharmacological treatment of gambling disorder are limited. Silymarin (derived from milk thistle) has antioxidant properties. The goal of the current study was to determine the efficacy and tolerability of silymarin in adults with gambling disorder. METHODS: Forty-three individuals (18 [41.9%] women; mean age=49.61 [±13.1] years) with gambling disorder entered an 8-week, double-blind, placebo-controlled study. Dosing of silymarin ranged from 150 to 300 mg twice a day. The primary outcome measure was the Yale Brown Obsessive Compulsive Scale Modified for Pathological Gambling (PG-YBOCS). Secondary outcome measures comprised the Gambling Symptom Assessment Scale and measures of depression and anxiety. Outcomes were examined using mixed-effect models. RESULTS: Silymarin did not statistically differentiate from the placebo on any of the outcome measures of interest, in terms of treatment group×time interactions. There was a robust response in the placebo group (57% reduction on the PG-YBOCS), and on average there was a 56% reduction in YBOCS score for the milk thistle. CONCLUSIONS: The findings of this study do not support the use of silymarin/milk thistle in the treatment of gambling disorder but highlight the large placebo response seen in gambling disorder. Treatment interventions for gambling disorder need to better understand and address the placebo response. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02337634.