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BACKGROUNDStudies have demonstrated the role of ghrelin in alcohol-related behaviors and consumption. Blockade of the growth hormone secretagogue receptor (GHSR), which is the ghrelin receptor, has been shown to decrease alcohol drinking and reward-related behaviors across several animal models. We previously conducted a human study testing a GHSR inverse agonist/competitive antagonist, PF-5190457, in individuals who are heavy drinkers and showed its safety when coadministered with alcohol. Here, we conducted a phase IIa experimental medicine study in patients with alcohol use disorder (AUD) to investigate the effects of PF-5190457 on alcohol- and food-related outcomes.METHODSForty-two individuals with AUD (n = 29 completers) participated in a randomized, double-blind, placebo-controlled study where they received PF-5190457 100mg b.i.d. (or placebo) in 2 counterbalanced, within-subject stages. Participants completed an alcohol cue-reactivity (CR) experiment in a bar-like laboratory and a virtual food choice experiment in a cafeteria-like virtual reality (VR) environment. A subset of participants (n = 12) performed a CR task during a brain functional MRI (fMRI) experiment.RESULTSPF-5190457 did not reduce cue-elicited alcohol craving. PF-5190457 reduced virtual calories selected (P = 0.04) in the VR environment. PF-5190457 did not influence neural activation during CR task in the fMRI experiment.CONCLUSIONThis study provides human evidence of the role of GHSR blockade in behaviors related to food selection and highlights the need for future investigations into targeting the ghrelin system in AUD.TRIAL REGISTRATIONClinicalTrials.gov (accession no. NCT02707055).FUNDINGNIDA and NIAAA ZIA-DA000635; National Center for Advancing Translational Sciences UH2/UH3-TR000963.

Objective: Increasing evidence indicates discrimination is an emerging risk factor for reducing psychological well-being. Negative affectivity is a personality trait that has been associated with discrimination. Yet, few studies to date have examined the longitudinal relationship between discrimination and personality. The current study addresses this gap by examining how general discrimination and negative affectivity influence each other longitudinally., Method: The Midlife in the United States (MIDUS) dataset was used for the current study. The MIDUS sample (N = 4244) was predominately white (90.7%), 52% female, and had an average age of 46 years old. Individuals completed follow-up measures 10 and 20 years after baseline. Data were analyzed using a random-intercept cross-lagged panel model., Results: Individuals that scored higher on trait negative affectivity also tended to score higher on perceived daily discrimination. We found general perceived discrimination at age 55 unidirectionally predicted changes in negative affectivity around retirement age, but not from age 45 to 55. In contrast, negative affectivity did not significantly predict increases in perceived discrimination at any timepoint., Conclusion: Our results indicate that perceived discrimination has pernicious impacts on well-being up to a decade later and may do so by increasing an individual's tendency to experience negative emotions (i.e., negative affectivity)., (© 2024 Wiley Periodicals LLC.)

Objective: Despite the well-established link between posttraumatic stress disorder (PTSD) and nonsuicidal self-injury (NSSI), little is known about factors that may lead to self-injury among trauma-exposed individuals. Moreover, no research to date has examined these relations in the context of the newly revised Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) PTSD criteria. Thus, the purpose of the current study was to explore the associations between DSM-5 PTSD symptom clusters (i.e., intrusion, avoidance, negative alterations in cognitions and mood, alterations in arousal and reactivity) and self-injury functions using a small sample of college students., Method: Participants ( N = 81) were recruited for a lifetime history of NSSI and trauma exposure., Results: Findings revealed a statistically significant path from PTSD avoidance symptoms to NSSI social functions and from PTSD negative alterations in cognitions and mood symptoms to NSSI intrapersonal functions, even after controlling for relevant covariates., Conclusions: Results of the current study highlight the importance of assessing for NSSI among trauma-exposed individuals. Considering that NSSI is a risk factor for suicidal behavior and potentially a clinically distinct diagnosis, future research should continue to explore these associations using larger, more diverse clinical samples. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Objective: Psychotherapy access, utilization, retention, and effectiveness require continued improvement, especially for groups for whom availability and outcomes may be currently suboptimal, including ethnoracial minorities. Further, ethnoracial status' intersectionality with other identity variables (e.g., gender) may relate to structural barriers to care and effectiveness of care, an area in need of further research., Method: The Florida State University Psychology Clinic, a low-cost population-facing treatment center, has routinely collected clinically relevant information on all consenting clients, including severity of clinical presentation at intake and over time, number of therapy sessions attended and of no-shows, premature termination, demographics, etc. A large sample of clients ( N = 2,076; 57% women; 67.9% non-Hispanic White) on whom we collected and entered at least some data, though missing data were common, has accrued. We conducted chi-square tests to examine treatment utilization gaps, analysis of variance to measure differences in intake severity, and analysis of covariance to measure differences in treatment effectiveness., Results: Based on the percentages of ethnoracial minority groups with mental disorders in the broader local community, we are falling short in outreach to Black clients, and when we do engage them, we retain them suboptimally. Once well engaged, however, results across groups suggest few differences in outcomes by ethnoracial status, gender, or their intersection. Ethnoracial match was associated with more sessions attended in Black people., Conclusions: Psychotherapy effectiveness has the potential to be optimized for everyone, and a promising direction in this regard is the case conceptualization of a cultural formulation interview and cultural humility mindset. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Cluster B personality traits often co-occur with psychopathic traits. However, few investigations have been conducted to understand the high co-occurrence of antisocial (ASPD), borderline (BPD), narcissistic (NPD), and histrionic (HPD) personality disorder traits and psychopathy. The triarchic model of psychopathy is a framework that focuses on dispositional constructs (meanness, boldness, and disinhibition) with neurobiological and developmental correlates that may be particularly useful in elucidating the overlap between Cluster B personality traits and psychopathy. This study investigated how the triarchic model relates to Cluster B personality traits. Two independent samples completed self-report measures of personality disorder traits. Sample 1 consists of 508 adults, and Sample 2 consists of 529 undergraduate students. Disinhibition positively predicted all Cluster B PDs. Meanness positively predicted ASPD, NPD, and BPD, and negatively predicted HPD. Boldness positively predicted ASPD, NPD, and HPD and negatively predicted BPD. Overall, our study provides insights into how these disorders may fit within new dimensional models of psychopathology and provides information regarding how transdiagnostic features (e.g., boldness) exist among the Cluster B personality disorder traits. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Sexual minorities are at heightened risk for nonsuicidal self-injury (NSSI), suicidal ideation and attempts. We tested whether sexual minority and heterosexual females differ on these characteristics. Sexual minority females (n = 45) had higher lifetime frequency of NSSI and higher thwarted belonginess compared to heterosexual females (n = 47). These specific factors may contribute to the higher rates of suicide attempts among sexual minorities than heterosexual individuals., (Copyright © 2022 Elsevier B.V. All rights reserved.)

In the psychological science field, there is substantial interest in quantifying individual differences in self-regulatory capacity because of its transdiagnostic relevance to various forms of psychopathology. Trait disinhibition and impulsiveness are popular conceptualizations of dispositions reflecting self-regulation of behavioral and emotional responding. In the literature, these constructs are often treated interchangeably because of their shared focus on general disconstraint and a lack of direct comparisons between measures of each. The current work used structural modeling to examine conceptual and empirical differences between 2 popular operationalizations of these traits in 2 samples ( N s = 400, 308), and employed regression and dominance analyses to compare their predictive relations with criterion measures of externalizing problems and negative affectivity (NA). Impulsigenic traits were related both to externalizing problems and NA, whereas trait disinhibition was selectively associated with externalizing. In a dominance analysis, trait disinhibition exhibited complete dominance over all impulsigenic traits in predicting externalizing problems. Conversely, multiple impulsigenic traits evidenced complete dominance over trait disinhibition in prediction of NA. The current work provides evidence that (a) disinhibition and impulsigenic traits are not interchangeable, (b) disinhibition specifically indexes propensity for externalizing problems, and (c) impulsigenic traits reflect a blend of externalizing and NA that appears relevant to diverse forms of psychopathology. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Genetics account for moderate variation of individual differences in developing alcohol use disorder (AUD), but it is unclear which genetic variations contribute to AUD risk. One candidate gene investigated due to its association with AUD is the dopamine D4 receptor gene (DRD4), which contains a 48-base pair variable number tandem repeat (VNTR) in exon 3 of its coding region. To date, no quantitative synthesis of the published literature on the effects of DRD4 VNTR variation on alcohol-related phenotypes has been conducted. MEDLINE, Embase, Web of Science, and PsycInfo were searched for studies that reported on alcohol craving, alcohol consumption, severity of AUD, and case-control (AUD versus no diagnosis of AUD) studies in DRD4L (seven repeats or more) carriers compared with DRD4S (six repeats or less) homozygotes. Random-effects meta-analysis was used for all analyses. A pooled sample size of 655 to 13,360 of 28 studies were included. Compared with DRD4S homozygotes, DRD4L carriers had increased number of drinking days (SMD: 0.205; 95% CI: 0.008 to 0.402), binge drinking days (SMD: 0.217; 95% CI: 0.0532 to 0.380), and severity of AUD (SMD: 0.143; 95% CI: 0.028 to 0.259). There was no difference between DRD4 VNTR genotypes on drinks per drinking day, largest number of drinks per day/occasion, and case-control analysis. It was not possible to conduct a meta-analysis of the craving data, but a systematic review of this literature found mixed results on DRD4 VNTR genotype effect. The present meta-analysis suggests DRD4 VNTR variation may be a risk factor for problematic alcohol use. Our findings are limited, however, by the absence of ancestry data from studies included in our analysis, precluding our ability to adjust for population stratification. Due to the likelihood of type I error in candidate gene approaches, our work highlights the critical need for studies with larger and more inclusive samples that account for sex and genetic ancestry to fully understand this relationship., (© 2019 Society for the Study of Addiction.)

Background : Cluster of differentiation 38 (CD38) is a transmembrane protein expressed in dopaminergic reward pathways in the brain, including the nucleus accumbens (NAc). The GG genotype of a common single nucleotide polymorphism (SNP) within CD38 , rs3796863, is associated with increased social reward. Objective : Examine whether CD38 rs3796863 and Cd38 knockout (KO) are associated with reward-related neural and behavioral phenotypes. Methods : Data from four independent human studies were used to test whether rs3796863 genotype is associated with: (1) intravenous alcohol self-administration (n = 64, 30 females), (2) alcohol-stimulated dopamine (DA) release measured using 11 C-raclopride positron emission tomography (n = 22 men), (3) ventral striatum (VS) response to positive feedback measured using a card guessing functional magnetic resonance imaging (fMRI) paradigm (n = 531, 276 females), and (4) resting state functional connectivity (rsfc) of the VS (n = 51, 26 females). In a fifth study, we used a mouse model to examine whether cd38 knockout influences stimulated DA release in the NAc core and dorsal striatum using fast-scanning cyclic voltammetry. Results : Relative to T allele carriers, G homozygotes at rs3796863 within CD38 were characterized by greater alcohol self-administration, alcohol-stimulated dopamine release, VS response to positive feedback, and rsfc between the VS and anterior cingulate cortex. High-frequency stimulation reduced DA release among Cd38 KO mice had reduced dopamine release in the NAc. Conclusion : Converging evidence suggests that CD38 rs3796863 genotype may increase DA-related reward response and alcohol consumption.

Background: While the role of attention-deficit/hyperactivity disorder (ADHD) as a risk factor for developing alcohol use disorder (AUD) has been established, the underlying pathways connecting the two are still not fully understood. Overlapping constructs such as impulsivity may explain the increased risk for developing AUD in individuals with ADHD., Methods: In this study, we assessed whether adult ADHD symptoms increase the odds of having a diagnosis of AUD. Furthermore, we tested whether facets of impulsivity explained the relationship between ADHD symptoms and alcohol dependence (AD) severity., Results: In a logistic regression of 749 participants (464 = AD, 285 = controls), overall adult ADHD symptoms, and more specifically, symptoms of hyperactivity/restlessness and problems with self-concept, increased the odds of having a diagnosis of AD. Within the AD sample, we found that impulsivity mediated the relationship between adult ADHD symptoms and AD severity. In particular, negative and positive urgency meditated the relationship of overall adult ADHD symptoms, and symptoms of hyperactivity/restlessness and problems with self-concept with AD severity., Conclusions: These results highlight the importance of looking at cohorts of ADHD symptoms and facets of impulsivity to assess the risk of developing AUD. They also suggest potential avenues for intervention strategies in individuals with preexisting adult ADHD symptoms who are seeking treatment for AUD., (Published 2017. This article is a U.S. Government work and is in the public domain in the USA.)