Elucidating mechanisms underlying the relationship between sleep disruption, alcohol use and psychiatric traits

Getting enough good quality sleep is vital for the healthy functioning of the brain and body. Unfortunately, we live in a golden age of insomnia, the most common sleep disorder which can be debilitating when chronic. Alcohol use is a major lifestyle factor associated with insomnia symptoms, but our understanding of the relationship between sleep and alcohol use remains limited. This thesis aims to shed light on the mechanisms underlying the association between sleep disruption, alcohol use and psychiatric traits. Studies I and II of the thesis confirm a strong link between alcohol use and sleep in the Older Finnish Twin Cohort by establishing that heavy and binge drinking are associated with poor sleep quality, short sleep duration and sleep medication use throughout adulthood. We find that moderate/heavy alcohol consumption predicts poor sleep and sleep medication use longitudinally. Further, cross-sectional associations between drinking and sleep variables are not fully explained by genetic and environmental influences shared by co-twins, with bivariate analyses emphasising the substantial contributions of genetic factors to individual differences in alcohol and insomnia symptoms during adulthood. Extending these findings in Study III, our analyses of FinnGen and UK Biobank suggest that Z-drugs, which are primarily used to treat insomnia, are strongly related to psychiatric traits at an epidemiological level and at the level of individual genetic variants. Our genome-wide association study identifies 27 genetic loci significantly associated with sleep medication use, located in genes previously linked to sleep and psychiatric traits. Genetic correlation analyses indicate a significant shared genetic background between the use of sleep medications and sleep problems, psychiatric and alcohol traits, while findings from Mendelian randomisation analyses suggest a causal relationship between Z-drugs purchases and psychiatric disorders, including depression, anxiety and schizophrenia. These studies collectively contribute to our understanding of the complex relationship between sleep, alcohol use and mental health, suggesting that sleep is not only substantially affected by long-term alcohol use but also that chronic sleep problems potentially contribute to severe mental health outcomes. This highlights the need for integrated treatment strategies that address the interplay between sleep, alcohol use, and mental health problems, while also considering genetic predispositions, to improve overall health and well-being.