Yu Nathan, Gordon Derek, Zou Hong, Chen Yingying, Yu Lei
Department of Genetics, Rutgers University, Piscataway, New Jersey, United States of America.
Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, Shanghai, People's Republic of China.
PLoS One. 2025 Apr 11;20(4):e0321506. doi: 10.1371/journal.pone.0321506. eCollection 2025.
Alcohol use disorders (AUDs) pose a significant public health challenge, with adolescence representing a critical period of vulnerability for the initiation of alcohol consumption. Variability in drinking behaviors among individuals complicates efforts to characterize developmental trajectories, limiting our understanding of underlying biological mechanisms.
This study aimed to identify and characterize distinct patterns of voluntary alcohol consumption in adolescent mice, using advanced statistical methods to model behavioral heterogeneity.
Thirty-five male CD-1 outbred mice were monitored for alcohol consumption using a two-bottle free-choice paradigm from early adolescence to young adulthood (4-11 weeks of age). Finite mixture modeling, using the method implemented in the software SAS Proc Traj, was applied to categorize individual drinking behaviors into trajectory groups based on Bayesian Information Criterion (BIC) and Bayesian Posterior Probabilities (BPP).
Three distinct drinking trajectory groups were identified: non-drinkers, late drinkers, and early drinkers. Non-drinkers exhibited consistently low alcohol consumption throughout the study, late drinkers showed a significant increase in alcohol intake during adolescence-to-adulthood transition, and early drinkers maintained high levels of consumption from the start. Notably, the late and early drinkers converged on similarly high consumption levels by the end of the observation period. These findings highlight the heterogeneity of drinking behaviors during adolescence and its developmental implications.
This study demonstrates the utility of finite mixture modeling in characterizing developmental trajectories of voluntary alcohol consumption in adolescent mice. The identification of distinct behavioral trajectory patterns provides a foundation for future investigations into the genetic, molecular, and neural mechanisms underpinning susceptibility to alcohol use disorders.
酒精使用障碍(AUDs)对公共卫生构成重大挑战,青春期是开始饮酒的关键脆弱期。个体饮酒行为的变异性使表征发育轨迹的努力变得复杂,限制了我们对潜在生物学机制的理解。
本研究旨在识别并表征青春期小鼠自愿饮酒的不同模式,使用先进的统计方法对行为异质性进行建模。
使用双瓶自由选择范式,从青春期早期到成年早期(4至11周龄)对35只雄性CD-1远交系小鼠的酒精消耗量进行监测。采用软件SAS Proc Traj中实现的方法进行有限混合建模,根据贝叶斯信息准则(BIC)和贝叶斯后验概率(BPP)将个体饮酒行为分类为轨迹组。
识别出三个不同的饮酒轨迹组:不饮酒者、晚期饮酒者和早期饮酒者。在整个研究过程中,不饮酒者的酒精消耗量始终较低;晚期饮酒者在青春期向成年期过渡期间酒精摄入量显著增加;早期饮酒者从一开始就保持较高的饮酒水平。值得注意的是,到观察期结束时,晚期和早期饮酒者的饮酒量趋于相似的高水平。这些发现突出了青春期饮酒行为的异质性及其发育意义。
本研究证明了有限混合建模在表征青春期小鼠自愿饮酒发育轨迹方面的实用性。识别出不同的行为轨迹模式为未来研究酒精使用障碍易感性的遗传、分子和神经机制奠定了基础。