Disgust sensitivity and behavioural inhibitory systems in binge eating disorder: associations with eating pathology.

Disgust sensitivity refers to how unpleasant a disgusting experience is to an individual and is involved in the development of many psychiatric conditions. Given its link with food ingestion, there is an interest in understanding how an individual's susceptibility to disgust relates to dietary habits. One possible mechanism giving rise to this association is through the effects negative emotions have on high-order cognitive processes, but few studies take this model into account. The aim of this study was to characterize general disgust sensitivity in a clinical binge eating disorder (BED) population, and explore whether disgust sensitivity relates to inhibitory control and eating pathology. Following a case-controlled study design, our results show that: (1) disgust sensitivity and its subscales do not differ between BED and healthy controls, (2) higher disgust sensitivity in BED relates to greater behavioural inhibition, (3) inhibitory control reaction times relate to aspects of eating pathology, and (4) inhibitory control does not mediate relationships between disgust sensitivity and BMI among participants with BED. Understanding the role of disgust sensitivity in BED may allow us to understand how negative emotion systems maintain dysregulated eating behaviours with the potential to inform emotion-regulation treatment approaches. Level of evidence: Level III: Evidence obtained from well-designed cohort or case-control analytic studies.

Multidimensional elements of impulsivity as shared and unique risk factors for food addiction and alcohol misuse.

Food addiction (FA) and alcohol misuse tend to co-occur, which suggests shared factors in the etiology and persistence of these health behaviors. One shared factor that has been linked to both is impulsivity, a multidimensional construct reflecting multiple facets of self-regulatory capacity. However, co-occurrence also raises issues of possible confounding if both domains are not considered concurrently, and the intersection between FA, alcohol misuse, and impulsivity has not been well characterized empirically. Therefore, the current study examined the intersection of FA, alcohol consequences, and multiple indicators of impulsivity. Participants were emerging adults reporting regular heavy episodic drinking recruited from Hamilton, Ontario (N = 730; ages 19.5-23). Participants completed measures of FA, alcohol problems, impulsive personality traits (i.e., Barratt Impulsiveness Scales, UPPS-P Impulsive Behavior Scales), impulsive choice (i.e., delay discounting), impulsive action (i.e., Go/NoGo task). Findings revealed a significant association between FA and alcohol-related consequences and both shared similar associations with specific impulsive personality traits (Positive and Negative Urgency, Lack of Premeditation, Motor and Attentional Impulsivity). However, alcohol-related consequences were uniquely associated with other impulsive personality traits (Lack of Perseverance, Sensation Seeking, Non-planning impulsivity) and impulsive choice, and FA was uniquely associated with impulsive action. Beyond alcohol-related consequences, FA was associated with additional variance in measures of impulsive personality traits (Positive and Negative Urgency, Lack of Premeditation, Motor Impulsivity, and Attentional Impulsivity) and impulsive action, but not impulsive choice. Overall, the current study reveals several common self-regulatory processes associated with both adverse drinking consequences and FA, and that the risk of inadvertent confounding appears to be limited.

A Comparison of Gambling-Related Cognitions and Behaviors in Gamblers from the United States and Spain.

Few studies have compared the clinical characteristics of gambling disorder (GD) from a cross-cultural perspective. In the present study, we aimed to examine differences in gambling-related cognitions, gambling preferences, GD severity and other clinical and sociodemographic variables in individuals with GD in the United States and Spain. Two groups of participants with GD (from the United States of America (US; n = 109) and Spain (n = 243) were compared using the South Oaks gambling screen and the gambling-related cognitions scale. In Spain, the prevalence of participants who reported only non-strategic gambling preferences was higher, whereas in the US, participants tended to engage in a wider breadth of gambling activities. Moreover, Spanish participants reported higher GD severity, while participants in the US endorsed greater gambling-related cognitions. Our findings suggest that there may jurisdictional or cultural differences in terms of gambling-related cognitions, gambling preferences, and GD severity levels among individuals in the US versus Spain. These differences, which may reflect cultural regulatory or other factors, should be investigated further, and considered when developing and implementing interventions for GD.

Neural Correlates of Personalized Spiritual Experiences.

Across cultures and throughout history, human beings have reported a variety of spiritual experiences and the concomitant perceived sense of union that transcends one's ordinary sense of self. Nevertheless, little is known about the underlying neural mechanisms of spiritual experiences, particularly when examined across different traditions and practices. By adapting an individualized guided-imagery task, we investigated neural correlates of personally meaningful spiritual experiences as compared with stressful and neutral-relaxing experiences. We observed in the spiritual condition, as compared with the neutral-relaxing condition, reduced activity in the left inferior parietal lobule (IPL), a result that suggests the IPL may contribute importantly to perceptual processing and self-other representations during spiritual experiences. Compared with stress cues, responses to spiritual cues showed reduced activity in the medial thalamus and caudate, regions associated with sensory and emotional processing. Overall, the study introduces a novel method for investigating brain correlates of personally meaningful spiritual experiences and suggests neural mechanisms associated with broadly defined and personally experienced spirituality.

Systematic review of the effects of acute stress in binge eating disorder.

Binge eating disorder (BED) is characterized by recurrent episodes of eating an excessive amount of food over a discrete time period, while feeling a loss of control over one's eating. Although stress is one of the most commonly reported triggers of binge eating in individuals with BED, there has been little work examining the stress response specifically in individuals with the disorder. In this review, we examine what is known about how individuals with BED respond to acute stressors. A systematic literature search identified 14 relevant articles that report on the effects of experimentally induced stress on objective measures. Dependent measures that have been examined include changes in the levels of hormones such as cortisol and ghrelin, cardiovascular function, ad libitum food intake and eating rate. In this review, we describe the published findings and discuss their implications in the context of the wider literature. Overall, we found partial evidence that BED is associated with a heightened response to stress. Given the inconsistencies between studies, we suggest that reported differences between individuals with and without BED might be driven by factors that are correlated with, but not specific to, BED. We suggest that two priorities for this research area are to identify factors that modulate the stress response in individuals with BED, and to address the underrepresentation of males in this literature.

An Exploratory Study of Relationships Among Five-Factor Personality Measures and Forms of Gambling in Adults With and Without Probable Pathological Gambling.

The present study explored relationships between personality domains and gambling forms in individuals with and without probable pathological gambling (PPG). Associations among personality domain scores obtained from the NEO Personality Inventory-Revised, endorsements of gambling activities on the South Oaks Gambling Screen (SOGS), and PPG as determined by the SOGS were examined with bivariate and logistic regression analyses. Compared to recreational gamblers, those with PPG scored significantly higher in neuroticism and lower in agreeableness and conscientiousness. Agreeableness was inversely associated with gambling on cards, sports, bingo, stock market, dice, and skill games. Conscientiousness was inversely associated with gambling on sports and animal racing. Extraversion was positively associated with gambling on cards, dice, and stocks. Neuroticism and openness were positively associated with gambling on animal racing and stock gambling, respectively. Significant interactions indicated stronger inverse associations between agreeableness and gambling in casinos, on sports, and on skill games and stronger positive associations between openness and gambling on stocks and skill games in individuals with PPG compared to those without. The results suggest different relationships between personality domain measures and specific forms of gambling in individuals with and without PPG. Future research efforts should examine how personality factors may be used to enhance policy, prevention, and treatment efforts.

Neurobiological features of binge eating disorder.

Biobehavioral features associated with binge-eating disorder (BED) have been investigated; however, few systematic reviews to date have described neuroimaging findings from studies of BED. Emerging functional and structural studies support BED as having unique and overlapping neural features as compared with other disorders. Neuroimaging studies provide evidence linking heightened responses to palatable food cues with prefrontal areas, particularly the orbitofrontal cortex (OFC), with specific relationships to hunger and reward-sensitivity measures. While few studies to date have investigated non-food-cue responses; these suggest a generalized hypofunctioning in frontostriatal areas during reward and inhibitory control processes. Early studies applying neuroimaging to treatment efforts suggest that targeting neural function underlying motivational processes may prove important in the treatment of BED.

A pilot study linking reduced fronto-Striatal recruitment during reward processing to persistent bingeing following treatment for binge-eating disorder.

OBJECTIVE: The primary purpose of this study was to examine neurobiological underpinnings of reward processing that may relate to treatment outcome for binge-eating disorder (BED). METHOD: Prior to starting treatment, 19 obese persons seeking treatment for BED performed a monetary incentive delay task during functional magnetic resonance imaging (fMRI). Analyses examined how the neural correlates of reward processing related to binge-eating status after 4-months of treatment. RESULTS: Ten individuals continued to report binge-eating (BEpost-tx ) following treatment and 9 individuals did not (NBEpost-tx ). The groups did not differ in body mass index. The BEpost-tx group relative to the NBEpost-tx group showed diminished recruitment of the ventral striatum and the inferior frontal gyrus during the anticipatory phase of reward processing and reduced activity in the medial prefrontal cortex during the outcome phase of reward processing. DISCUSSION: These results link brain reward circuitry to treatment outcome in BED and suggest that specific brain regions underlying reward processing may represent important therapeutic targets in BED.

Adolescent alcohol-drinking frequency and problem-gambling severity: adolescent perceptions regarding problem-gambling prevention and parental/adult behaviors and attitudes.

BACKGROUND: The study examined in adolescents how alcohol-drinking frequency relates to gambling-related attitudes and behaviors and perceptions of both problem-gambling prevention strategies and adult (including parental) behaviors/attitudes. METHODS: A survey assessing alcohol, gambling, and health and functioning measures in 1609 high school students. Students were stratified into low-frequency/nondrinking and high-frequency-drinking groups, and into low-risk and at-risk/problematic gambling groups. RESULTS: High-frequency drinking was associated with at-risk/problematic gambling (χ(2)(1,N = 1842) = 49.22, P < .0001). High-frequency-drinking versus low-frequency/nondrinking adolescents exhibited more permissive attitudes towards gambling (e.g., less likely to report multiple problem-gambling prevention efforts to be important). At-risk problematic gamblers exhibited more severe drinking patterns and greater likelihood of acknowledging parental approval of drinking (χ(2)(1, N = 1842) = 31.58, P < .0001). Problem-gambling severity was more strongly related to gambling with adults among high-frequency-drinking adolescents (odds ratio [OR] = 3.17, 95% confidence interval [95% CI] = [1.97, 5.09]) versus low-frequency/nondrinking (OR = 1.86, 95% CI = [0.61, 2.68]) adolescents (interaction OR = 1.78, 95% CI = [1.05, 3.02]). CONCLUSIONS: Interrelationships between problematic drinking and gambling in youth may relate to more permissive attitudes across these domains. Stronger links between at-risk/problem gambling and gambling with adults in the high-frequency-drinking group raises the possibility that interventions targeting adults may help mitigate youth gambling and drinking.

Reward learning capacity in a community sample of individuals who use cannabis.

Cannabis use has been linked to deficient reward processing; however, little is known about its relation to the specific construct of reward learning, in which behavior is modified through associating novel stimuli with a positive outcome. The probabilistic reward task was used to objectively evaluate reward learning in 38 individuals who use recreational cannabis and 34 control comparison participants from the community. Reward learning was evidenced by the development of a response bias, which indicates the propensity to modulate behavior as a function of prior reinforcement. Both cannabis and control groups demonstrated reward learning, with no group differences in response bias development. Among cannabis participants, trending significant relationships between greater chronicity, r(36) = -.30, p = .077, self-reported potency, r(19) = -.33, p = .052, and poorer reward learning were found. Nonsignificant relationships were found between reward learning and frequency, age of initiation, weekly quantity or Cannabis Use Disorder Identification Test-Revised (CUDIT-R) scores (all p > .05). The ability to form noncannabis reward associations is promising for the success of therapeutic interventions for problematic cannabis use; however, indications of severity of use in relation to poorer reward learning suggests a need for a better pharmacological and pharmacokinetic understanding of cannabis. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

A preliminary investigation of Stroop-related intrinsic connectivity in cocaine dependence: associations with treatment outcomes.

BACKGROUND: Cocaine-dependent individuals demonstrate neural and behavioral differences compared to healthy comparison subjects when performing the Stroop color-word interference test. Stroop measures also relate to treatment outcome for cocaine dependence. Intrinsic connectivity analyses assess the extent to which task-related regional brain activations are related to each other in the absence of defining a priori regions of interest. OBJECTIVE: This study examined 1) the extent to which cocaine-dependent and non-addicted individuals differed on measures of intrinsic connectivity during fMRI Stroop performance; and 2) the relationships between fMRI Stroop intrinsic connectivity and treatment outcome in cocaine dependence. METHODS: Sixteen treatment-seeking cocaine-dependent patients and matched non-addicted comparison subjects completed an fMRI Stroop task. Between-group differences in intrinsic connectivity were assessed and related to self-reported and urine-toxicology-based cocaine-abstinence measures. RESULTS: Cocaine-dependent patients vs. comparison subjects showed less intrinsic connectivity in cortical and subcortical regions. When adjusting for individual degree of intrinsic connectivity, cocaine-dependent vs. comparison subjects showed relatively greater intrinsic connectivity in the ventral striatum, putamen, inferior frontal gyrus, anterior insula, thalamus and substantia nigra. Non-mean-adjusted intrinsic-connectivity measures in the midbrain, thalamus, ventral striatum, substantia nigra, insula and hippocampus negatively correlated with measures of cocaine abstinence. CONCLUSION: The diminished intrinsic connectivity in cocaine-dependent vs. comparison subjects suggests poorer communication across brain regions during cognitive-control processes. In mean-adjusted analyses, the cocaine-dependent group displayed relatively greater Stroop-related connectivity in regions implicated in motivational processes in addictions. The relationships between treatment outcomes and connectivity in the midbrain and basal ganglia suggest that connectivity represents a potential treatment target.

Phenobarbital for alcohol withdrawal management in the emergency department: A systematic review of direct evidence for the SAEM GRACE initiative.

OBJECTIVES: Alcohol withdrawal syndrome (AWS) is a commonly presenting condition in the emergency department (ED) and can have severe complications, including mortality. Benzodiazepines are first-line medications for treating AWS but may be unavailable or insufficient. This systematic review evaluates the direct evidence assessing the utility of phenobarbital for treating AWS in the ED. METHODS: A systematic search was conducted and designed according to the patient-intervention-comparator-outcome (PICO) question: (P) adults (≥18 years old) presenting to the ED with alcohol withdrawal; (I) phenobarbital (including adjunctive); (C) benzodiazepines or no intervention; and (O) AWS complications, admission to a monitored setting, control of symptoms, adverse effects, and adjunctive medications. Two reviewers independently assessed articles for inclusion and conducted risk of bias assessments for included studies. RESULTS: From 70 potentially relevant articles, seven studies met inclusion criteria: three retrospective cohort studies, two retrospective chart reviews, and two randomized controlled trials (RCTs), one examining phenobarbital monotherapy and one examining adjunctive phenobarbital. Across the retrospective cohort studies, treatment of AWS with phenobarbital resulted in lower odds of a subsequent ED visit. The retrospective chart reviews indicated that phenobarbital was associated with higher discharge rate compared to benzodiazepine-only treatments. For the two RCTs, phenobarbital did not differ significantly from benzodiazepine for most outcomes, although concomitant treatment with phenobarbital was associated with lower benzodiazepine use and intensive care unit admission. The heterogeneous designs and small number of studies prevented quantitative synthesis. CONCLUSIONS: Relatively few studies provide direct evidence on the utility of phenobarbital for AWS in the ED, but the evidence that exists generally suggests that it is a reasonable and appropriate approach. Additional RCTs and other methodologically rigorous investigations are needed for more definitive direct evidence.

Anti-craving medications for alcohol use disorder treatment in the emergency department: A systematic review of direct evidence for SAEM GRACE.

OBJECTIVES: Alcohol-related concerns commonly present to the emergency department (ED), with a subset of individuals experiencing the symptoms of an alcohol use disorder (AUD). As such, examining the efficacy of pharmacological anti-craving treatment for AUD in the ED is of increasing interest. The objective of this systematic review was to evaluate the direct evidence assessing the efficacy of providing anti-craving medications for AUD treatment in the ED. METHODS: A systematic search was conducted according to the patient-intervention-control-outcome question: (P) adults (≥18 years old) presenting to the ED with an AUD (including suspected AUD); (I) anti-craving medications (i.e., naltrexone, acamprosate, gabapentin); (C) no prescription or placebo; (O) reduction of repeat ED visits, engagement in addiction services, reductions in heavy drinking days, reductions in any drinking and amount consumed (or abstinence), and in relapse. Two reviewers independently assessed articles for inclusion and conducted risk of bias assessments for included studies. RESULTS: From 143 potentially relevant articles, 6 met inclusion criteria: 3 clinical trials, and 3 case studies. The clinical trials identified evaluated oral versus extended-release naltrexone, monthly extended-release naltrexone injections, and disulfiram. Both oral and extended-release naltrexone resulted in decreased alcohol consumption. Monthly extended-release naltrexone injections resulted in significant improvements in drinking and quality of life. Although out of scope, the disulfiram studies identified did not result in an improvement in drinking in comparison to no medication. CONCLUSIONS: Overall, there are few studies directly examining the efficacy of anti-craving medications for AUD in the ED, although the limited evidence that exists is supportive of naltrexone pharmacotherapy, particularly extended-release injection formulation. Additional randomized controlled trials are necessary for substantive direct evidence on anti-craving medication initiation in the ED.

A preliminary study of the neural correlates of the intensities of self-reported gambling urges and emotions in men with pathological gambling.

Although self-reported gambling urge intensities have clinical utility in the treatment of pathological gambling (PG), prior studies have not investigated their neural correlates. Functional magnetic resonance imaging (fMRI) was conducted while 10 men with PG and 11 control comparison (CON) men viewed videotaped scenarios of gambling, happy or sad content. Participants rated the intensity of their emotions and motivations and reported the qualities of their responses. Relative to the CON group, the PG group reported similar responses to sad and happy scenarios, but stronger emotional responses and gambling urges when viewing the gambling scenarios. Correlations between self-reported responses and brain activations were typically strongest during the period of reported onset of emotional/motivational response and more robust in PG than in CON subjects for all conditions. During this epoch, corresponding with conscious awareness of an emotional/motivational response, subjective ratings of gambling urges in the PG group were negatively correlated with medial prefrontal cortex activation and positively correlated with middle temporal gyrus and temporal pole activations. Sadness ratings in the PG group correlated positively with activation of the medial orbitofrontal cortex, middle temporal gyrus, and retrosplenial cortex, while self-reported happiness during the happy videos demonstrated largely inverse correlations with activations in the temporal poles. Brain areas identified in the PG subjects have been implicated in explicit, self-referential processing and episodic memory. The findings demonstrate different patterns of correlations between subjective measures of emotions and motivations in PG and CON subjects when viewing material of corresponding content, suggesting in PG alterations in the neural correlates underlying experiential aspects of affective processing.

Mental Health Over Time and Financial Concerns Predict Change in Online Gambling During COVID-19.

This study examined online gambling behavior during COVID-19 land-based gambling restrictions and associations with changes in mental health, impacts on household income due to the pandemic, financially focused motivations, and symptoms of gambling problems. A repeated online survey was administered to adult gamblers in Ontario, Canada. Wave 1 was conducted at the beginning of the first COVID-19 lockdown (April 2020) and wave 2 in August 2020. Respondents (N = 940) completed validated self-report questionnaires related to depression and anxiety, financial motivation, financial impacts due to the pandemic, online gambling behaviors, and problem gambling symptomatology. A cluster analysis identified three subgroups: no online gambling (subgroup 1), engagement in a range of gambling games online and change in gambling involvement (i.e., some increased and some decreased gambling; subgroup 2), and predominantly online lottery play with no change in online gambling (subgroup 3). Respondents who reported increased anxiety and depression symptom severity between the two waves and those who experienced greater symptoms of problem gambling and negative impacts on household income due to COVID-19 were most likely to be found in subgroup 2. Greater financial focus was also noted in this group. Results indicate a link between change in online gambling involvement during COVID-19 and increased mental health problems, elevated problem gambling severity, negative impacts on household income, and a greater financially focused self-concept. These results may help generate novel research questions examining short and long-term effects of the pandemic on online behaviors that inform policy and practice.

The stress-response-dampening effects of placebo.

This experiment used both biological and self-report measures to examine how alcohol modifies stress responses, and to test whether the interaction between these two factors alters risk-taking in healthy young adults. Participants were divided into stress or no-stress conditions and then further divided into one of three beverage groups. The alcohol group consumed a binge-drinking level of alcohol; the placebo group consumed soda, but believed they were consuming alcohol; the sober group was aware that they were not consuming alcohol. Following beverage consumption, the stress group was subjected to the Trier Social Stress Test (TSST) while the no-stress group completed crossword puzzles; all participants subsequently completed a computerized risk-taking task. Exposure to the TSST significantly increased salivary levels of the hormone cortisol and the enzyme alpha-amylase, as well as subjective self-ratings of anxiety and tension. In the stress condition, both placebo and intoxicated groups reported less tension and anxiety, and exhibited a smaller increase in cortisol, following the TSST than did the sober group. Thus, the expectation of receiving alcohol altered subjective and physiological responses to the stressor. Neither alcohol nor stress increased risk taking, however the sober group demonstrated lower risk-taking on the computer task on the second session. These findings clearly demonstrate that the expectation of alcohol (placebo) alters subsequent physiological responses to stress.

A review of effort-based decision-making in eating and weight disorders.

Effort-based decision-making provides a framework to understand the mental computations estimating the amount of work ("effort") required to obtain a reward. The aim of the current review is to systematically synthesize the available literature on effort-based decision-making across the spectrum of eating and weight disorders. More specifically, the current review summarises the literature examining whether 1) individuals with eating disorders and overweight/obesity are willing to expend more effort for rewards compared to healthy controls, 2) if particular components of effort-based decision-making (i.e. risk, discounting) relate to specific binge eating conditions, and 3) how individual differences in effort and reward -processing measures relate to eating pathology and treatment measures. A total of 96 studies were included in our review, following PRISMA guidelines. The review suggests that individuals with binge eating behaviours 1) are more likely to expend greater effort for food rewards, but not monetary rewards, 2) demonstrate greater decision-making impairments under risk and uncertainty, 3) prefer sooner rather than delayed rewards for both food and money, and 4) demonstrate increased implicit 'wanting' for high fat sweet foods. Finally, individual differences in effort and reward -processing measures relating to eating pathology and treatment measures are also discussed.

Food addiction in a large community sample of Canadian adults: prevalence and relationship with obesity, body composition, quality of life and impulsivity.

BACKGROUND AND AIMS: Parallels between the persistent overconsumption of food and addictive drugs have given rise to the notion of food addiction. In a large community sample of Canadian adults, the current study examined the prevalence of food addiction and its relationship with obesity, quality of life and multiple indicators of impulsivity. A secondary goal was to analyze differences between obese and non-obese individuals with and without food addiction. DESIGN: Cross-sectional in-person assessment. SETTING: Hamilton, Ontario, Canada. PARTICIPANTS: A total of 1432 community adults (age = mean ± standard deviation = 38.93 ± 13.7; 42% male) recruited from the general community using print, bus and internet advertisements. MEASUREMENTS: Yale Food Addiction Scale 2.0, anthropometrics (including body mass index), body composition (e.g. body fat, muscle mass, body water), World Health Organization Quality of Life scale and impulsivity measures, including impulsive personality traits, delay discounting and behavioral inhibition. FINDINGS: The prevalence of food addiction was 9.3% and substantially below that of obesity (32.7%), although food addiction was significantly more common among obese individuals (18.5%, P < 0.001). Food addiction was associated with significantly lower quality of life in all domains (ßs = -0.21 to -0.34, Ps < 0.001) and significantly higher impulsive personality traits, particularly negative and positive urgency (ßs = 0.37 and 0.30, Ps < 0.001). Subgroup contrasts within both the obese and non-obese strata revealed that food addiction was associated with significantly lower quality of life in all domains (Ps < 0.001). Food addiction among non-obese individuals was also associated with higher body mass index (P < 0.001). CONCLUSION: In a general community sample, food addiction was present in slightly fewer than one in 10 individuals, approximately one-third the prevalence of obesity, but with twice the prevalence among obese individuals. Food addiction appears to be associated with substantively lower quality of life and elevations in impulsivity, particularly in deficits in emotional regulation.

GABAergic polygenic risk for cocaine use disorder is negatively correlated with precuneus activity during cognitive control in African American individuals.

Impaired cognitive control has been implicated in cocaine use disorder (CUD). GABAergic treatments have been proposed for CUD. Here we examined relationships between GABAergic genes and neural correlates of cognitive control in CUD. We analyzed two independent African American cohorts: one of >3000 genomewide-genotyped subjects with substance dependence and another of 40 CUD and 22 healthy control (HC) subjects who were exome-array genotyped and completed an fMRI Stroop task. We used five association thresholds to select variants of GABAergic genes in the reference cohort, yielding five polygenic risk scores (i.e., CUD-GABA-PRSs) for the fMRI cohort. At p < 0.005, the CUD-GABA-PRSs, which aggregated relative risks of CUD from 89 variants harboring in 16 genes, differed between CUD and HC individuals in the fMRI sample (p = 0.013). This CUD-GABA-PRS correlated inversely with Stroop-related activity in the left precuneus in CUD (r = -80.58, pFWE < 0.05) but not HC participants. Post-hoc seed-based connectivity analysis of the left precuneus identified reduced functional connectivity to the posterior cingulate cortex (PCC) in CUD compared to HC subjects (p = 0.0062) and the degree of connectivity correlated with CUD-GABA-PRSs in CUD individuals (r = 0.287, p = 0.036). Our findings suggest that the GABAergic genetic risk of CUD in African Americans relates to precuneus/PCC functional connectivity during cognitive control. Identification of these GABAergic processes may be relevant targets in CUD treatment. The novel identification of 16 GABAergic genes may be investigated further to inform treatment development efforts for this condition that currently has no medication with a formal indication for its treatment.

Discrete Roles for Impulsivity and Compulsivity in Gambling Disorder.

Background and Objective: Complex associations between gambling disorder (GD) and impulsivity have been identified. However, little is known regarding how compulsivity associates with different impulsivity domains in GD. In this study, we examined associations between self-reported and behavioral measures of impulsivity-assessed through the Barratt Impulsiveness Scale (BIS-11) and the Experiential Discounting Task (EDT), respectively- and compulsivity-measured using the Padua Inventory and the Wisconsin Card Sorting Test (WCST), respectively-, in an adult sample with GD (N = 132, 94 men and 38 women, ages ranging from 18 to 69 years). GD severity was assessed using the South Oaks Gambling Screen. Methods: Structural Equation Modeling was used to examine relationships between impulsivity and compulsivity measures, age, and GD severity. Results: BIS-11 non-planning and BIS-11 total scores positively correlated with GD severity. The standardized coefficients for the SEM showed direct positive contributions of BIS-11 non-planning, Padua and EDT scores to GD severity. Only participants' ages directly contributed to WCST perseverative errors, and no direct or indirect effects were found with respect to GD severity. Conclusion: The findings suggest that specific aspects of impulsivity and compulsivity contribute to GD severity. Interventions specifically targeting domains that are most relevant to GD severity may improve treatment outcomes.