ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
To reduce the spread of COVID-19 transmission, government agencies in the United States (US) recommended precautionary guidelines, including wearing masks and social distancing to encourage the prevention of the disease. However, compliance with these guidelines has been inconsistent. This correlational study examined whether individual differences in risky decision-making and motivational propensities predicted compliance with COVID-19 preventative behaviors in a sample of US adults (N = 404). Participants completed an online study from September through December 2020 that included a risky choice decision-making task, temporal discounting task, and measures of appropriate mask-wearing, social distancing, and perceived risk of engaging in public activities. Linear regression results indicated that greater temporal discounting and risky decision-making were associated with less appropriate mask-wearing behavior and social distancing. Additionally, demographic factors, including personal experience with COVID-19 and financial difficulties due to COVID-19, were also associated with differences in COVID-19 preventative behaviors. Path analysis results showed that risky decision-making behavior, temporal discounting, and risk perception collectively predicted 55% of the variance in appropriate mask-wearing behavior. Individual differences in general decision-making patterns are therefore highly predictive of who complies with COVID-19 prevention guidelines.
