ABSTRACT Alcohol consumption imposes a substantial public health burden in the United States, yet public and political support for alcohol control policies remains limited despite a strong evidence base. This stems partly from methodological challenges, including difficulties measuring policy implementation and enforcement, accounting for local variation, and assessing long‐term effects, and partly from gaps in translating findings into actionable insights for policymakers and the public. In this narrative review, we highlight three methodological approaches that can strengthen policy‐relevant alcohol research: system dynamics modeling, spatial analysis, and artificial intelligence (AI) tools for policy surveillance. Each is illustrated through a policy example (minimum unit pricing, regulating alcohol outlet density, and limiting hours of sale) to demonstrate how these methods can generate actionable insights for policymakers and the public. We conclude with recommendations for conducting policy‐relevant, methodologically rigorous research: codeveloping research questions with stakeholders, grounding research in specific theories of change, accounting for policy restrictiveness and enforcement, aligning methods with research questions, and planning for dissemination from the outset. Together, these strategies can help bridge the gap between evidence and action, ultimately strengthening support for effective alcohol control policies.
ABSTRACT Background The widespread prevalence of alcohol use disorder (AUD) and availability of treatments contrasts with limited treatment utilization. Here, in the Collaborative Studies on the Genetics of Alcoholism (COGA), we examined the extent to which genetic factors (i.e., family‐based heritability ( h 2 GCTA ), polygenic scores [PGS]) are associated with individual differences in AUD treatment utilization that could be leveraged to target intervention efforts. Methods Non‐proband COGA participants with a lifetime Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM‐5) AUD diagnosis, whose genomic ancestry resembled that of European (EUR‐like: N = 3148; 370 nuclear families; 222 extended family pedigrees) and African (AFR‐like: N = 962; 92 nuclear families; 79 extended family pedigrees) reference panels were selected for analyses. AUD treatment h 2 GCTA and associations with PGS (i.e., alcohol involvement, cigarette use, psychopathology, externalizing behavior, and cognition‐related) were estimated, along with between‐ and within‐family effects of the PGSs. Results AUD treatment was heritable ( h 2 GCTA = 0.36; SE = 0.06) and positively associated with PGS for problematic alcohol use, drinks/week, externalizing behavior, depression, anxiety and schizophrenia/bipolar (ORs > 1.12) while being negatively associated with education attainment (OR = 0.90) in the EUR‐like sample after accounting for AUD severity ( p FDR ≤ 0.04). When all significant PGSs were simultaneously included, only alcohol PGSs remained significant. There were no significant PGS associations in within‐family analyses. Despite a nominally significant positive association with cigarettes per day, no PGSs were associated with AUD treatment following FDR adjustment in the AFR‐like sample. Conclusions Genetic factors underlying alcohol use influence AUD treatment utilization, but this phenotype is largely not significantly associated with current estimates of polygenic scores for other complex traits; this suggests a potential unique genetic etiology requiring further investigation with a genome‐wide association study. The lack of significant within‐family PGS associations may have likely arisen from power reductions due to restricting the sample to full siblings. Together, these findings highlight potential facets influencing the underutilization of AUD treatment.
ABSTRACT Background Decades of prior work have indicated associations between thyroid hormone axis dysregulation and alcohol use disorder (AUD). Specifically, disruptions in thyroid hormone levels are related to altered mood, compulsion, craving, and relapse in patients with AUD. Likewise, modulating thyroid hormones in preclinical models can impact ethanol (EtOH) consumption. Recently, we have shown that daily treatment with central nervous system selective thyroid hormone receptor‐beta agonist, Sob‐AM2, can reduce daily EtOH consumption and preference in male and female C57BL6/J mice at a 1.0 mg/kg dose. However, it is unclear if lower doses can attain reductions in drinking and if the effects of Sob‐AM2 habituate with chronic dosing over time. Furthermore, as thyroid hormone signaling within the brain can influence many behaviors, the precise mechanisms driving Sob‐AM2's influence on EtOH drinking remain unclear. Methods In the present study, we tested if treatment with a lower dose of Sob‐AM2, 0.3 mg/kg, for 9 days would be sufficient to reduce EtOH intake and preference and if these effects would be sustained over a two‐week period. In addition, we tested whether the effects of Sob‐AM2 are exerted via altering ETOH elimination from blood, influencing caloric consumption, affecting taste for sucrose, or altering avoidance of a bitter tastant. Results We found that Sob‐AM2 treatment for 9 days was sufficient to reduce both EtOH intake and preference while increasing water and total fluid intake, and these effects were also present at 23 days of treatment. Meanwhile, treatment with Sob‐AM2 did not result in alterations of EtOH elimination rate, nor did it affect food consumption, sucrose consumption, or quinine avoidance in a way that explains reductions in EtOH consumption. Conclusions These results demonstrate that agonism of central thyroid hormone receptor‐beta selectively decreases voluntary EtOH consumption and may indicate a promising novel therapeutic approach for the treatment of AUD.
