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.

Behavioral economic analysis of legal and illegal cannabis demand in Spanish young adults with hazardous and non-hazardous cannabis use.

BACKGROUND: In October 2021, a legal framework that regulates cannabis for recreational purposes in Spain was proposed, but research on its potential impacts on cannabis use is currently limited. This study examined the reliability and discriminant validity of two Marijuana Purchase Tasks (MPTs) for measuring hypothetical legal and illegal cannabis demand, and to examine differences in demand of both commodities in young adults at hazardous vs. non-hazardous cannabis use risk levels. METHODS: A total of 171 Spanish young adults [Mage = 19.82 (SD = 1.81)] with past-month cannabis use participated in a cross-sectional study from September to November 2021. Two 27-item MPTs were used to estimate hypothetical demand for legal and illegal cannabis independently. The Cannabis Use Disorder Identification Test (CUDIT-R) was used to assess hazardous cannabis use and test for discriminant validity of the MPTs. Reliability analyses were conducted using Classical Test Theory (Cronbach's alpha) and Item Response Theory (Item Information Functions). RESULTS: The MPT was reliable for measuring legal (α = 0.94) and illegal (α = 0.90) cannabis demand. Breakpoint (price at which demand ceases), and Pmax (price associated with maximum expenditure) were the most sensitive indicators to discriminate participants with different levels of the cannabis reinforcing trait. No significant differences between legal and illegal cannabis demand in the whole sample were observed, but hazardous vs. non-hazardous users showed higher legal and illegal demand, and decreased Breakpoint and Pmax if cannabis were legal vs illegal. CONCLUSION: The MPT exhibits robust psychometric validity and may be useful to inform on cannabis regulatory science in Spain.

Longitudinal examination of alcohol demand and alcohol-related reinforcement as predictors of heavy drinking and adverse alcohol consequences in emerging adults.

BACKGROUND AND AIMS: Behavioral economic theory predicts that high alcohol demand and high proportionate alcohol-related reinforcement are important determinants of risky alcohol use in emerging adults, but the majority of research to date has been cross-sectional in nature. The present study investigated prospective and dynamic relationships between alcohol demand and proportionate alcohol-related reinforcement in relation to heavy drinking days and alcohol problems. DESIGN: Longitudinal cohort with assessments every 4 months for 20 months. SETTING: Ontario, Canada. PARTICIPANTS: Emerging adults reporting regular heavy episodic drinking (n = 636, Mage = 21.44; 55.8% female). MEASUREMENTS: Heavy drinking days (HDD; Daily Drinking Questionnaire), alcohol problems (Brief Young Adult Alcohol Consequences Questionnaire), alcohol demand (Alcohol Purchase Task) and proportionate alcohol-related reinforcement (Activity Level Questionnaire). FINDINGS: Linear mixed effects models revealed that behavioral economic indicators and alcohol-related outcomes significantly decreased over the study, consistent with 'aging out' of risky alcohol use. Random intercept cross-lagged panel models revealed significant between-person relationships, such that higher alcohol demand and alcohol-related reinforcement were positively associated with HDD and alcohol problems (random intercepts = 0.187-0.534, Ps < 0.01). Moreover, alcohol demand indicators (particularly the rate of change in elasticity of the demand curve, as measured by α, and the maximum expenditure, Omax) and proportionate alcohol-related reinforcement significantly forecasted changes in HDD at all time points (|ßs| = 0.063-0.103, Ps < 0.05) in cross-lagged relationships, with bidirectional associations noted for the rate of change in elasticity (ßs = -0.085 to -0.104, Ps < 0.01). Proportionate alcohol-related reinforcement also significantly forecasted changes in alcohol problems at all time points (ßs = 0.072-0.112, Ps < 0.01). CONCLUSIONS: Multiple behavioral economic indicators (demand elasticity, maximum expenditure and reinforcement ratio) forecast changes in heavy episodic drinking and alcohol problems over the course of emerging adulthood. These results further implicate alcohol demand and proportionate alcohol-related reinforcement as etiologically and developmentally important mechanisms in alcohol use trajectories.

Changing cannabis legislation in Canada and a longitudinal look at "regular" cannabis use in patients with eating disorders.

Regular cannabis use (CU), defined as "weekly or more often", is associated with a number of negative mental health outcomes. In the last decade, Canada legalized first medical and then recreational CU. Despite higher prevalence in mental health populations, little research has documented changes in frequency of CU with progressive legalization of cannabis. This study examined rates of CU in a sample of 843 treatment-seeking patients with eating disorders (ED) in an outpatient setting between 2004 and 2020. Across ED diagnoses, segmented regression indicated a significant break-point in regular CU in 2014, commensurate with the relaxation of medical cannabis laws. Regular CU increased from 4.9 % to 23.7 % from 2014 to 2020; well above the stable 6 % found in the general population. No significant break-point was observed in either alcohol or illicit substance use over the same time period. Significant increases in regular CU were found in patients with anorexia nervosa and binge eating disorder, while regular use remained stable in patients with bulimia nervosa. Comorbid psychiatric diagnoses did not increase odds of regular CU. Findings suggest certain patient groups with mental illness may be at risk of engaging in high frequency use in the context of legislation implying medical benefits of cannabis.