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.

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.

Post-traumatic growth among pediatric transplant recipients and their caregivers: A scoping review.

BACKGROUND: Pediatric transplantation can be a stressful process for patients and caregivers. Some individuals may experience post-traumatic stress symptoms (PTSS) and post-traumatic growth (PTG) as a result. Although post-traumatic stress disorder (PTSD) has been well-studied in this population, the purpose of the present scoping review is to provide a first synthesis of the existing literature on PTG in pediatric transplant populations. METHODS: We conducted a literature search of PsycINFO and Scopus in May 2023. Eligible articles must have included a sample of solid organ transplant (SOT) or stem cell transplant (SCT) recipients under age 18, siblings of recipients, or caregivers; and must have examined PTG. RESULTS: Twenty-three studies were identified, and nine studies met inclusion criteria and were included in the review (n = 5 cross sectional; n = 4 qualitative). Cross-sectional studies examined demographic, mental health, and medical correlates of PTG in children and caregivers. PTG was correlated with PTSS among caregivers. Qualitative studies identified themes along each of the five factors of PTG. CONCLUSION: Findings overwhelmingly focused on caregiver PTG. Qualitative study findings align with the theoretical model of PTG. Additional research is needed to investigate PTG in siblings of children with a transplant and associations between PTG and medication adherence. This scoping review provides insight into positive change processes following a transplant among children and their caregivers.

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.

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.

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.

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.

Leveraging genetic data to investigate molecular targets and drug repurposing candidates for treating alcohol use disorder and hepatotoxicity.

BACKGROUND: Novel treatments for alcohol use disorder (AUD) and alcohol-related liver disease (ALD) are greatly needed. Genetic information can improve drug discovery rates by facilitating the identification of novel biological targets and potential drugs for repurposing. METHODS: The present study utilized a recently developed Bayesian approach, Integrative Risk Gene Selector (iRIGS), to identify additional risk genes for alcohol consumption using SNPs from the largest alcohol consumption GWAS to date (N = 941,280). iRIGS incorporates several genomic features and closeness of these genes in network space to compute a posterior probability for protein coding genes near each SNP. We subsequently used the Target Central Resource Database to search for drug-protein interactions for these newly identified genes and previously identified risk genes for alcohol consumption. RESULTS: We identified several genes that are novel contributions to the previously published alcohol consumption GWAS. Namely, ACVR2A, which is critical for liver function and linked to anxiety and cocaine self-administration, and PRKCE, which has been linked to alcohol self-administration. Notably, only a minority of the SNPs (18.4 %) were linked to genes with confidence (>0.75), underscoring the need to apply multiple methods to assign function to loci. Finally, some previously identified risk genes for alcohol consumption code for proteins that are implicated in liver function and are targeted by drugs, some of which are candidates for managing hepatotoxicity. CONCLUSIONS: This study demonstrates the value of incorporating regulatory information and drug-protein interaction data to highlight additional molecular targets and drug repurposing candidates for treating AUD and ALD.

Associations of cigarette smoking with gray and white matter in the UK Biobank.

Cigarette smoking is associated with increased risk for myriad health consequences including cognitive decline and dementia, but research on the link between smoking and brain structure is nascent. In the current study, we assessed the relationship of cigarette smoking with gray matter (GM) and white matter (WM) in the UK Biobank, controlling for numerous confounding demographic and health variables. We used negative-binomial regression to model the association of cigarette smoking (having ever smoked regularly, cigarettes per day, and duration smoked) with GM and WM (GM N = 19,615; WM N = 17,760), adjusting for confounders. Ever smoked and duration were associated with smaller total GM volume. Ever smoked was associated with reduced volume of the right VIIIa cerebellum and elevated WM hyperintensity volume. Smoking duration was associated with reduced total WM volume. Regarding specific tracts, ever smoked was associated with reduced fractional anisotropy in the left cingulate gyrus part of the cingulum, left posterior thalamic radiation, and bilateral superior thalamic radiation, and increased mean diffusivity in the middle cerebellar peduncle, right medial lemniscus, bilateral posterior thalamic radiation, and bilateral superior thalamic radiation. This study identified significant associations of cigarette exposure with global measures of GM and WM, and select associations of ever smoked, but not cigarettes per day or duration, with specific GM and WM regions. By controlling for important sociodemographic and health confounders, such as alcohol use, this study identifies distinct associations between smoking and brain structure, highlighting potential mechanisms of risk for common neurological sequelae (e.g., dementia).