Candidate Genes from an FDA-Approved Algorithm Fail to Predict Opioid Use Disorder Risk in Over 450,000 Veterans.

Importance: Recently, the Food and Drug Administration gave pre-marketing approval to algorithm based on its purported ability to identify genetic risk for opioid use disorder. However, the clinical utility of the candidate genes comprising the algorithm has not been independently demonstrated. Objective: To assess the utility of 15 variants in candidate genes from an algorithm intended to predict opioid use disorder risk. Design: This case-control study examined the association of 15 candidate genetic variants with risk of opioid use disorder using available electronic health record data from December 20, 1992 to September 30, 2022. Setting: Electronic health record data, including pharmacy records, from Million Veteran Program participants across the United States. Participants: Participants were opioid-exposed individuals enrolled in the Million Veteran Program (n = 452,664). Opioid use disorder cases were identified using International Classification of Disease diagnostic codes, and controls were individuals with no opioid use disorder diagnosis. Exposures: Number of risk alleles present across 15 candidate genetic variants. Main Outcome and Measures: Predictive performance of 15 genetic variants for opioid use disorder risk assessed via logistic regression and machine learning models. Results: Opioid exposed individuals (n=33,669 cases) were on average 61.15 (SD = 13.37) years old, 90.46% male, and had varied genetic similarity to global reference panels. Collectively, the 15 candidate genetic variants accounted for 0.4% of variation in opioid use disorder risk. The accuracy of the ensemble machine learning model using the 15 genes as predictors was 52.8% (95% CI = 52.1 - 53.6%) in an independent testing sample. Conclusions and Relevance: Candidate genes that comprise the approved algorithm do not meet reasonable standards of efficacy in predicting opioid use disorder risk. Given the algorithm's limited predictive accuracy, its use in clinical care would lead to high rates of false positive and negative findings. More clinically useful models are needed to identify individuals at risk of developing opioid use disorder.

N-acetylcysteine as a treatment for substance use cravings: A meta-analysis.

N-acetylcysteine (NAC) may serve as a novel pharmacotherapy for substance use and substance craving in individuals with substance use disorders (SUDs), possibly through its potential to regulate glutamate. Though prior meta-analyses generally support NAC's efficacy in reducing symptoms of craving, individual trials have found mixed results. The aims of the this updated meta-analysis were to (1) examine the efficacy of NAC in treating symptoms of craving in individuals with a SUD and (2) explore subgroup differences, risk of bias, and publication bias across trials. Database searches of PubMed, Cochrane Library, and ClinicalTrials.gov were conducted to identify relevant randomized control trials (RCTs). The meta-analysis consisted of 9 trials which analyzed data from a total of 623 participants. The most targeted substance in the clinical trials was alcohol (3/9; 33.3%), followed by tobacco (2/9; 22.2%) and multiple substances (2/9; 22.2%). Meta-analysis, subgroup analyses, and leave-one-out analyses were conducted to examine treatment effect on craving symptoms and adverse events (AEs). Risk of bias assessments, Egger's tests, and funnel plot tests were conducted to examine risk of bias and publication bias. NAC did not significantly outperform placebo in reducing symptoms of craving in the meta-analysis (SMD = 0.189, 95% CI = -0.015 - 0.393). Heterogeneity was very high in the meta-analysis (99.26%), indicating that findings may have been influenced by clinical or methodological differences in the study protocols. Additionally, results indicate that there may be publication bias present. There were no between-group differences in risk of AEs. Overall, our findings are contrary to those of prior meta-analyses, suggesting limited impact of NAC on substance craving. However, the high heterogeneity and presence of publication bias identified warrants cautious interpretation of the meta-analytic outcomes.

Alcohol use disorder and body mass index show genetic pleiotropy and shared neural associations.

Background: The prevalence of co-occurring heavy alcohol consumption and obesity is increasing in the United States. Despite neurobiological overlap in the regulation of alcohol consumption and eating behavior, alcohol- and body mass index (BMI)-related phenotypes show no or minimal genetic correlation. We hypothesized that the lack of genetic correlation is due to mixed effect directions of variants shared by AUD and BMI. Methods: We applied MiXeR, to investigate shared genetic architecture between AUD and BMI in individuals of European ancestry. We used conjunctional false discovery rate (conjFDR) analysis to detect loci associated with both phenotypes and their directional effect, Functional Mapping and Annotation (FUMA) to identify lead single nucleotide polymorphisms (SNPs), Genotype-Tissue Expression (GTEx) samples to examine gene expression enrichment across tissue types, and BrainXcan to evaluate the shared associations of AUD and BMI with brain image-derived phenotypes. Results: MiXeR analysis indicated polygenic overlap of 80.9% between AUD and BMI, despite a genetic correlation (r g ) of -.03. ConjFDR analysis yielded 56 lead SNPs with the same effect direction and 76 with the opposite direction. Of the 132 shared lead SNPs, 53 were novel for both AUD and BMI. GTEx analyses identified significant overexpression in the frontal cortex (BA9), hypothalamus, cortex, anterior cingulate cortex (BA24), hippocampus, and amygdala. Amygdala and caudate nucleus gray matter volumes were significantly associated with both AUD and BMI in BrainXcan analyses. Conclusions: More than half of variants significantly associated with AUD and BMI had opposite directions of effect for the traits, supporting our hypothesis that this is the basis for their lack of genetic correlation. Follow-up analyses identified brain regions implicated in executive functioning, reward, homeostasis, and food intake regulation. Together, these findings clarify the extensive polygenic overlap between AUD and BMI and elucidate several overlapping neurobiological mechanisms.

Evaluating the Acceptability and Feasibility of Collecting Passive Smartphone Data to Estimate Psychological Functioning in U.S. Service Members and Veterans: A Pilot Study.

INTRODUCTION: This study investigated the acceptability and feasibility of digital phenotyping in a military sample with a history of traumatic brain injury and co-occurring psychological and cognitive symptoms. The first aim was to evaluate the acceptability of digital phenotyping by (1a) quantifying the proportion of participants willing to download the app and rates of dropout and app discontinuation and (1b) reviewing the stated reasons for both refusing and discontinuing use of the app. The second aim was to investigate technical feasibility by (2a) characterizing the amount and frequency of transferred data and (2b) documenting technical challenges. Exploratory aim 3 sought to leverage data on phone and keyboard interactions to predict if a participant (a) is depressed and (b) has depression that improves over the course of the study. MATERIALS AND METHODS: A passive digital phenotyping app (Mindstrong Discovery) functioned in the background of the participants' smartphones and passively collected phone usage and typing kinematics data. RESULTS: Fifteen out of 16 participants (93.8%) consented to install the app on their personal smartphone devices. Four participants (26.7%) discontinued the use of the app partway through the study, primarily because of keyboard usability and technical issues. Fourteen out of 15 participants (93.3%) had at least one data transfer, and the median number of days with data was 40 out of a possible 57 days. The exploratory machine learning models predicting depression status and improvement in depression performed better than chance. CONCLUSIONS: The findings of this pilot study suggest that digital phenotyping is acceptable and feasible in a military sample and provides support for future larger investigations of this technology.

A high-resolution PheWAS approach to alcohol-related polygenic risk scores reveals mechanistic influences of alcohol reinforcing value and drinking motives.

AIMS: This study uses a high-resolution phenome-wide approach to evaluate the motivational mechanisms of polygenic risk scores (PRSs) that have been robustly associated with coarse alcohol phenotypes in large-scale studies. METHODS: In a community-based sample of 1534 Europeans, we examined genome-wide PRSs for the Alcohol Use Disorders Identification Test (AUDIT), drinks per week, alcohol use disorder (AUD), problematic alcohol use (PAU), and general addiction, in relation to 42 curated phenotypes. The curated phenotypes were in seven categories: alcohol consumption, alcohol reinforcing value, drinking motives, other addictive behaviors, commonly comorbid psychiatric syndromes, impulsivity, and personality traits. RESULTS: The PRS for each alcohol phenotype was validated via its within-sample association with the corresponding phenotype (adjusted R2s = 0.35-1.68%, Ps = 0.012-3.6 × 10-7) with the exception of AUD. All PRSs were positively associated with alcohol reinforcing value and drinking motives, with the strongest effects from AUDIT-consumption (adjusted R2s = 0.45-1.33%, Ps = 0.006-3.6 × 10-5) and drinks per week PRSs (adjusted R2s = 0.52-2.28%, Ps = 0.004-6.6 × 10-9). Furthermore, the PAU and drinks per week PRSs were positively associated with adverse childhood experiences (adjusted R2s = 0.6-0.7%, Ps = 0.0001-4.8 × 10-4). CONCLUSIONS: These results implicate alcohol reinforcing value and drinking motives as genetically-influenced mechanisms using PRSs for the first time. The findings also highlight the value of dissecting genetic influence on alcohol involvement through diverse phenotypic risk pathways but also the need for future studies with both phenotypic richness and larger samples.

Healthcare utilization and readiness outcomes among soldiers with post-deployment at-risk drinking, by multimorbidity class.

Although alcohol use disorder (AUD) regularly co-occurs with other conditions, there has not been investigation of specific multimorbidity classes among military members with at-risk alcohol use. We used latent class analysis (LCA) to cluster 138,929 soldiers with post-deployment at-risk drinking based on their co-occurring psychological and physical health conditions and indicators of alcohol severity. We examined the association of these multimorbidity classes with healthcare utilization and military readiness outcomes. Latent class analysis was conducted on 31 dichotomous indicators capturing alcohol use severity, mental health screens, psychological and physical health diagnoses, and tobacco use. Longitudinal survival analysis was used to examine the relative hazards of class membership regarding healthcare utilization (e.g., emergency department visit, inpatient stay) and readiness outcomes (e.g., early separation for misconduct). Latent class analysis identified five classes: Class 1 -Relatively Healthy (51.6 %); Class 2 - Pain/Tobacco (17.3 %); Class 3 - Heavy Drinking/Pain/Tobacco (13.1 %); Class 4 - Mental Health/Pain/Tobacco (12.7 %); and Class 5 - Heavy Drinking/Mental Health/Pain/Tobacco (5.4 %). Musculoskeletal pain and tobacco use were prevalent in all classes, though highest in Classes 2, 4, and 5. Classes 4 and 5 had the highest hazards of all outcomes. Class 5 generally exhibited slightly higher hazards of all outcomes than Class 4, demonstrating the exacerbation of risk among those with heavy drinking/AUD in combination with mental health conditions and other multimorbidity. This study provides new information about the most common multimorbidity presentations of at-risk drinkers in the military so that targeted, individualized care may be employed. Future research is needed to determine whether tailored prevention and treatment approaches for soldiers in different multimorbidity classes is associated with improved outcomes.

Diagnostic profiles associated with long-term opioid therapy in active duty servicemembers.

INTRODUCTION: Over-prescription of opioids has diminished in recent years; however, certain populations remain at high risk. There is a dearth of research evaluating prescription rates using specific multimorbidity patterns. OBJECTIVE: To identify distinct clinical profiles associated with opioid prescription and evaluate their relative odds of receiving long-term opioid therapy. DESIGN: Retrospective analysis of the complete military electronic health record. We assessed demographics and 26 physiological, psychological, and pain conditions present during initial opioid prescription. Latent class analysis (LCA) identified unique clinical profiles using diagnostic data. Logistic regression measured the odds of these classes receiving long-term opioid therapy. SETTING: All electronic health data under the TRICARE network. PARTICIPANTS: All servicemembers on active duty during fiscal years 2016 through 2019 who filled at least one opioid prescription. MAIN OUTCOME MEASURES: Number and qualitative characteristics of LCA classes; odds ratios (ORs) from logistic regression. We hypothesized that LCA classes characterized by high-risk contraindications would have significantly higher odds of long-term opioid therapy. RESULTS: A total of N = 714,446 active duty servicemembers were prescribed an opioid during the study window, with 12,940 (1.8%) receiving long-term opioid therapy. LCA identified five classes: Relatively Healthy (82%); Musculoskeletal Acute Pain and Substance Use Disorders (6%); High Pain, Low Mental Health Burden (9%); Low Pain, High Mental Health Burden (2%), and Multisystem Multimorbid (1%). Logistic regression found that, compared to the Relatively Healthy reference, the Multisystem Multimorbid class, characterized by multiple opioid contraindications, had the highest odds of receiving long-term opioid therapy (OR = 9.24; p < .001; 95% confidence interval [CI]: 8.56, 9.98). CONCLUSION: Analyses demonstrated that classes with greater multimorbidity at the time of prescription, particularly co-occurring psychiatric and pain disorders, had higher likelihood of long-term opioid therapy. Overall, this study helps identify patients most at risk for long-term opioid therapy and has implications for health care policy and patient care.

Uncommon Protein-Coding Variants Associated With Suicide Attempt in a Diverse Sample of U.S. Army Soldiers.

BACKGROUND: Suicide is a societal and public health concern of global scale. Identifying genetic risk factors for suicide attempt can characterize underlying biology and enable early interventions to prevent deaths. Recent studies have described common genetic variants for suicide-related behaviors. Here, we advance this search for genetic risk by analyzing the association between suicide attempt and uncommon variation exome-wide in a large, ancestrally diverse sample. METHODS: We sequenced whole genomes of 13,584 soldiers from the Army STARRS (Army Study to Assess Risk and Resilience in Servicemembers), including 979 individuals with a history of suicide attempt. Uncommon, nonsilent protein-coding variants were analyzed exome-wide for association with suicide attempt using gene-collapsed and single-variant analyses. RESULTS: We identified 19 genes with variants enriched in individuals with history of suicide attempt, either through gene-collapsed or single-variant analysis (Bonferroni padjusted < .05). These genes were CIB2, MLF1, HERC1, YWHAE, RCN2, VWA5B1, ATAD3A, NACA, EP400, ZNF585A, LYST, RC3H2, PSD3, STARD9, SGMS1, ACTR6, RGS7BP, DIRAS2, and KRTAP10-1. Most genes had variants across multiple genomic ancestry groups. Seventeen of these genes were expressed in healthy brain tissue, with 9 genes expressed at the highest levels in the brain versus other tissues. Brains from individuals deceased from suicide aberrantly expressed RGS7BP (padjusted = .035) in addition to nominally significant genes including YWHAE and ACTR6, all of which have reported associations with other mental disorders. CONCLUSIONS: These results advance the molecular characterization of suicide attempt behavior and support the utility of whole-genome sequencing for complementing the findings of genome-wide association studies in suicide research.

Longitudinal Associations Between Perceived Discrimination and Suicidality in Youth.

Research among adults reveals robust associations between discrimination and suicidality. However, the relationship between discrimination and suicidality is understudied in youth. Participants in the Adolescent Brain Cognitive Development study (n = 10  312) completed a measure of discrimination based on multiple attributes. The Kiddie Schedule for Affective Disorders and Schizophrenia was administered 1 year later to assess depressive disorders and suicidality (ideation and behavior). Logistic regressions, adjusting for age, sex, race/ethnicity, family income, lifetime depressive disorders, and body composition were conducted. Adjusting for covariates, discrimination based on weight (OR: 2.19), race/ethnicity/color (OR: 3.21), and sexual orientation (OR: 3.83) were associated with greater odds of reporting suicidality 1 year later (ps < 0.025). Nationality-based discrimination was not significantly associated with suicidality. Compared with those reporting no discrimination, youths reporting discrimination based on 2 or more attributes had nearly 5 times greater odds of recent suicidality (OR: 4.72; P < .001). The current study highlights the deleterious impacts of discrimination on mental health among youths reporting multiple forms of discrimination.

Test-retest reliability of the neuroanatomical correlates of impulsive personality traits in the adolescent brain cognitive development study.

While the neuroanatomical correlates of impulsivity in youths have been examined, there is little research on whether those correlates are consistent across childhood/adolescence. The current study uses data from the age 11/12 (N = 7,083) visit of the Adolescent Brain Cognitive Development Study to investigate the replicability of previous work (Owens et al., 2020) the neuroanatomical correlates of impulsive personality traits identified at age 9/10. Neuroanatomy was measured using structural and diffusion magnetic resonance imaging, and impulsive personality was measured using the UPPS-P Impulsive Behavior Scale. Replicability was quantified using three Open Science Collaboration replication criteria, intraclass correlations, and elastic net regression modeling to make predictions across timepoints. Replicability was highly variable among traits: The neuroanatomical correlates of positive urgency showed substantial similarity between ages 9/10 and 11/12, negative urgency and sensation seeking showed moderate similarity across ages, and (lack of) premeditation and perseverance showed substantial dissimilarity across ages. In all cases, effect sizes between impulsive traits and brain variables were small. These findings suggest that, even for studies with large sample sizes and the same participant pool, the replicability of brain-behavior correlations across a 2-year period cannot be assumed. This may be due to developmental changes across the two timepoints or false-positive/false-negative results at one or both timepoints. These results also highlight an array of neuroanatomical structures that may be important to impulsive personality traits across development from childhood into adolescence. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

The prospective relationship between weight-based discrimination and eating pathology among youth.

Among adults and adolescents, weight-based discrimination is associated with disordered eating. However, these relationships remain understudied in children. Given that weight-based discrimination is commonly reported among youth, and that childhood is a crucial developmental period for the onset of disordered eating, the current study assessed prospective associations between weight-based discrimination and eating pathology among participants in the Adolescent Brain Cognitive Development Study. At the one-year visit, children indicated whether they had experienced discrimination due to their weight within the past year. Parents completed a computerized clinical interview to determine the presence of sub-or-full threshold eating disorders (AN, BN, and BED) among their children. At the two-year visit, children completed the same assessment. Height and fasting weight were obtained. Logistic regressions, adjusting for age, sex, race/ethnicity, family income, BMI%ile, and parent-reported presence of the respective eating disorder at one-year, were conducted to assess the associations between weight-based discrimination and eating pathology. Participants were 10,299 children who completed measures at both the one- and two-year visits (Mage at one-year: 10.92 ± 0.64, 47.6 % female, 45.9 % racial/ethnic minority). The presence of weight-based discrimination, reported by 5.6 % (n = 574) of children, was significantly associated with a greater likelihood of reporting AN, BN, and BED one-year later (ORs: 1.94-4.91). Findings suggest that weight-based discrimination may confer additional risk for the onset of disordered eating, above and beyond the contribution of body weight. Intersectional research is needed to examine the role of multiple forms of discrimination in relation to the development of eating pathology.

Resting-state network analysis of suicide attempt history in the UK Biobank.

BACKGROUND: Prior research has identified altered brain structure and function in individuals at risk for self-directed violence thoughts and behaviors. However, these studies have largely utilized healthy controls and findings have been inconsistent. Thus, this study examined differences in resting-state functional network connectivity among individuals with lifetime suicide attempt(s) v. lifetime self-directed violence thoughts alone. METHODS: Using data from the UK Biobank, this study utilized a series of linear regressions to compare individuals with lifetime suicide attempt(s) (n = 566) v. lifetime self-directed violence thoughts alone (n = 3447) on within- and between- network resting-state functional connectivity subnetworks. RESULTS: There were no significant between-group differences for between-network, within-network, or whole-brain functional connectivity after adjusting for age, sex, ethnicity, and body mass index and performing statistical corrections for multiple comparisons. Resting-state network measures may not differentiate between individuals with lifetime suicide attempt(s) and lifetime self-directed violence thoughts alone. CONCLUSIONS: Null findings diverge from results reported in smaller neuroimaging studies of suicide risk, but are consistent with null findings in other large-scale studies and meta-analyses. Strengths of the study include its large sample size and stringent control group. Future research on a wider array of imaging, genetic, and psychosocial risk factors can clarify relative contributions of individual and combined variables to suicide risk and inform scientific understanding of ideation-to-action framework.

Leveraging related health phenotypes for polygenic prediction of impulsive choice, impulsive action, and impulsive personality traits in 1534 European ancestry community adults.

Impulsivity refers to a number of conceptually related phenotypes reflecting self-regulatory capacity that are considered promising endophenotypes for mental and physical health. Measures of impulsivity can be broadly grouped into three domains, namely, impulsive choice, impulsive action, and impulsive personality traits. In a community-based sample of ancestral Europeans (n = 1534), we conducted genome-wide association studies (GWASs) of impulsive choice (delay discounting), impulsive action (behavioral inhibition), and impulsive personality traits (UPPS-P), and evaluated 11 polygenic risk scores (PRSs) of phenotypes previously linked to self-regulation. Although there were no individual genome-wide significant hits, the neuroticism PRS was positively associated with negative urgency (adjusted R2 = 1.61%, p = 3.6 × 10-7 ) and the educational attainment PRS was inversely associated with delay discounting (adjusted R2 = 1.68%, p = 2.2 × 10-7 ). There was also evidence implicating PRSs of attention-deficit/hyperactivity disorder, externalizing, risk-taking, smoking cessation, smoking initiation, and body mass index with one or more impulsivity phenotypes (adjusted R2 s: 0.35%-1.07%; FDR adjusted ps = 0.05-0.0006). These significant associations between PRSs and impulsivity phenotypes are consistent with established genetic correlations. The combined PRS explained 0.91%-2.46% of the phenotypic variance for individual impulsivity measures, corresponding to 8.7%-32.5% of their reported single-nucleotide polymorphism (SNP)-based heritability, suggesting a non-negligible portion of the SNP-based heritability can be recovered by PRSs. These results support the predictive validity and utility of PRSs, even derived from related phenotypes, to inform the genetics of impulsivity phenotypes.

The Mediating Role of Family Acceptance and Conflict on Suicidality among Sexual and Gender Minority Youth.

INTRODUCTION: Prior research suggests sexual and gender minority (SGM) youth are profoundly impacted by levels of parental support. This study assessed mediating effects of generalized family acceptance and conflict on lifetime suicidal behaviors among a large diverse sample comprising both SGM and non-SGM youth in early adolescence, when intervention to optimize family dynamics may be critical. MATERIALS: Using data from the first-year follow-up of the Adolescent Brain Cognitive Development Study based in the United States, mediation was tested using a binary logistic regression model fitted with a generalized structural equation. Models included SGM status as the independent variable, family acceptance or family conflict sum score as the mediator, and the presence of lifetime suicidal behaviors as the dependent variable. Models adjusted for age, birth-assigned sex (as reported by the parent/guardian), and race/ethnicity. RESULTS: Of 11,235 youths, lifetime suicidal behaviors were reported by 1.5% (n = 164). Youths with SGM identities reported 40% less parental acceptance and 47% greater family conflict, compared to non-SGM peers. Both parental acceptance and family conflict partially mediated associations between SGM identification and odds of lifetime suicidal behavior (ps = .001). CONCLUSIONS: Identification of modifiable risk factors for suicidality in this vulnerable population, including parental acceptance and family conflict, is critical to improving health outcomes. Clinicians should work with SGM youth and their families starting in childhood to optimize family dynamics and bolster acceptance to potentially reduce adverse health outcomes. HIGHLIGHTSYouths with SGM identity reported 40% less parental acceptance than non-SGM peers.Parental acceptance was associated with lower odds of lifetime suicidal behaviors.Family factors partially mediated associations between SGM status and suicidal behaviors.

Beliefs and Perceived Barriers Regarding Psychedelic-assisted Therapy in a Pilot Study of Service Members and Veterans With a History of Traumatic Brain Injury.

INTRODUCTION: Posttraumatic stress disorder (PTSD) and depression are common in service members and veterans, and the response to currently available treatments is often modest at best. Recent studies suggest potential benefit with psychedelic-assisted therapies (PATs), particularly 3,4-methylenedioxymethamphetamine-assisted therapy for PTSD and psilocybin-assisted therapy for depression. This study examined beliefs and perceived barriers regarding PAT among service members and veterans to inform the delivery of these treatments if they are approved by the FDA. MATERIALS AND METHODS: Twenty-one service members and veterans (67% male, 81% White, and 43% active duty) with a history of traumatic brain injury and co-occurring cognitive and psychological symptoms completed a measure assessing baseline knowledge and views of PAT, read a brief psychoeducation regarding PAT, and then responded to questions related to their beliefs and perceived barriers to PAT. RESULTS: Before psychoeducation, participants reported a neutral view of psychedelic drugs (M = 2.76; range: 1-5), PAT (M = 3.33), and interest in PAT (M = 3.10). After psychoeducation, participants reported a significantly more positive view of psychedelic drugs (M = 3.24, P = .014) and interest in PAT (M = 3.67, P = .016). Overall, participants indicated that they would support PAT availability in medical settings if proven beneficial (M = 4.52; 5 = "agree strongly") and they would support a loved one engaging in PAT (M = 4.29). The most frequently reported health concerns were concern of long-term effects (43%), fear of losing their mind (33%), fear of personality changes (33%), and fear of traumatic brain injury complications (24%). The most frequently endorsed barriers were time commitment, transportation, financial concerns, work, and childcare (33%-19%), with 48% reporting no barriers. CONCLUSIONS: This is the first study to explore beliefs and perceived barriers regarding PAT among service members and veterans. These results indicate that military populations may be interested in PAT, particularly if psychoeducation and outreach regarding these treatments occurred. If FDA approved, it will be important to facilitate command support and address logistical barriers to ensure appropriate access within military contexts.

Neuroeconomic predictors of smoking cessation outcomes: A preliminary study of delay discounting in treatment-seeking adult smokers.

Large proportions of smokers are unsuccessful in evidence-based smoking cessation treatment and identifying prognostic predictors may inform improvements in treatment. Steep discounting of delayed rewards (delay discounting) is a robust predictor of poor smoking cessation outcome, but the underlying neural predictors have not been investigated. Forty-one treatment-seeking adult smokers completed a functional magnetic resonance imaging (fMRI) delay discounting paradigm prior to initiating a 9-week smoking cessation treatment protocol. Behavioral performance significantly predicted treatment outcomes (verified 7-day abstinence, n = 18; relapse, n = 23). Participants in the relapse group exhibited smaller area under the curve (d = 1.10) and smaller AUC was correlated with fewer days to smoking relapse (r = 0.56, p < 0.001) Neural correlates of discounting included medial and dorsolateral prefrontal cortex, posterior cingulate, precuneus and anterior insula, and interactions between choice type and relapse status were present for the dorsolateral prefrontal cortex, precuneus and the striatum. This initial investigation implicates differential neural activity in regions associated with frontal executive and default mode activity, as well as motivational circuits. Larger samples are needed to improve the resolution in identifying the neural underpinnings linking steep delay discounting to smoking cessation.

The association between child alcohol sipping and alcohol expectancies in the ABCD study.

BACKGROUND: Underage drinking is a serious societal concern, yet relatively little is known about child sipping of alcohol and its relation to beliefs about alcohol. The current study aimed to (1) examine the contexts in which the first sip of alcohol occurs (e.g., type of alcohol, who provided sip, sip offered or taken without permission); (2) examine the association between sipping and alcohol expectancies; and (3) explore how different contexts of sipping are related to alcohol expectancies. We expected to find that children who had sipped alcohol would have increased positive expectancies and reduced negative expectancies compared to children who had never sipped alcohol. METHODS: Data were derived from the 2.0 release of the Adolescent Brain Cognitive Development (ABCD) study, a longitudinal study of children in the United States. We utilized data from 4,842 children ages 9-11; 52% were male, 60% were White, 19% were Hispanic/Latinx, and 9% were Black/African American. RESULTS: We found that 22% of the sample had sipped alcohol. Children reported sipping beer most frequently, and the drink most often belonged to the child's father. We found that children who had sipped had higher positive alcohol expectancies than children who had not while accounting for variables related to alcohol expectancies. Child sipping was not significantly associated with negative expectancies and the context of the first sip of alcohol was not significantly associated with positive and negative expectancies. CONCLUSIONS: Providing sips of alcohol to children is associated with them having more favorable expectations about drinking.

The association of engagement in substance use treatment with negative separation from the military among soldiers with post-deployment alcohol use disorder.

BACKGROUND: Alcohol use disorder (AUD) reduces the health of soldiers and the readiness of the Armed Forces. It remains unknown if engagement in substance use treatment in the Military Health System improves retention in the military. METHODS: The sample consisted of active duty soldiers returning from an Afghanistan/Iraq deployment in fiscal years 2008-2010 who received an AUD diagnosis within 150 days of completing a post-deployment health re-assessment survey (n = 4,726). A Heckman probit procedure was used to examine predictors of substance use treatment initiation and engagement in accordance with Healthcare Effectiveness Data and Information Set (HEDIS) criteria. Cox proportional hazard modeling was used to examine the association between treatment engagement and retention, defined as a negative separation for a non-routine cause (e.g., separation due to misconduct, poor performance, disability) from the military in the two years following the index AUD diagnosis. RESULTS: 40 % of soldiers meeting HEDIS AUD criteria initiated and 24 % engaged in substance use treatment. Among soldiers diagnosed with AUD, meeting criteria for treatment engagement was associated with a significantly higher hazard of having a negative separation compared to soldiers who did not engage in treatment. CONCLUSIONS: Rates of initiation and engagement in substance use treatment for post-deployment AUD were relatively low. Soldiers with AUD who engaged in substance use treatment were more likely to have a negative separation from the military than soldiers with AUD who did not engage. Our findings imply that in the study cohort, treatment did not mitigate negative career consequences of AUD.