Alcohol use disorders (AUDs) affect over 100 million people worldwide with alcohol use accounting for 4.2% of global disability adjusted life years (DALYs) (Degenhardt et al. 2018).
Adolescence and young adulthood is recognised as a critical window for the development of AUDs due to the vulnerability of the corticolimbic system to alcohol-induced damage during this period (Nixon and McClain, 2010). AUDs commonly develop during late adolescence and early adulthood, with a median age of onset for alcohol abuse of 21 and alcohol dependence of 23 (Kessler et al, 2005). Adolescent alcohol use has both immediate and longer-term effects on the development of AUDs. In adolescents that used alcohol for the first time between the ages of 11 and 14 the rate of alcohol dependence measured ten years post exposure was 15.9% in contrast to those who used alcohol for the first time after the age of 19, where rates of alcohol dependence ten years post exposure were only 1% (DeWit et al, 2000). A prospective cohort study in the UK demonstrated that following adjustment for other predictors, frequent teenage alcohol use and antisocial behaviour held persisting and independent associations with later alcohol dependence (Bonomo et al 2004).
Early life stress and traumatic experiences are widely recognised to contribute to AUDs in humans (Viner and Taylor, 2007). In the UK the association between trauma and substance use disorders has been recognised by the Department of Health with services required to use a trauma-informed model of addiction care (Clinical Guidelines on Drug Misuse and Dependence Update 2017). In epidemiological studies the presence of Adverse Childhood Events (ACEs) is associated with an earlier onset of alcohol use and increased levels of alcohol consumption (Rothman et al. 2008). ACEs specifically linked to alcohol use include physical abuse, sexual abuse, having a mentally ill household member, substance abuse in the home, and parental discord or divorce (Rothman et al. 2008). All forms of childhood trauma act as risk factors for adolescent binge drinking; with earlier adverse alcohol consumption potentially lying on the causal pathway between trauma and alcohol use disorders (Shin et al. 2009). One pathway that may explain how early life adversity and adolescent alcohol use lead to AUD in adulthood is through long term changes in gene expression as a result of epigenetic modification. Exposure to early life adversity and adolescent alcohol use independently lead to long-term epigenetic changes (Houtepen et al. 2016, Kyzar et al. 2016). Markers of early life adversity have been demonstrated to show conserved epigenetic changes between human and rat hippocampal tissue providing scope for translation between preclinical and epidemiological studies (Suderman et al. 2012).
This study aims to explore the interaction between early life adversity and adolescent alcohol use in the development of alcohol use disorders in adulthood using the ALSPAC cohort. This study will quantify ACEs in the ALSPAC cohort using previously developed approaches (Houtepen et al. 2018) and develop an approach to quantify adolescent alcohol use. These measures will be used as predictors of a diagnosis of AUD using DSM V criteria at age 25. Epigenetic associations with early life adversity and adolescent alcohol use will be explored with the intention of using these findings to bridge between this study and a parallel programme of preclinical experiments taking place Department of Physiology, Pharmacology and Neuroscience at the University of Bristol.