Abstract
INTRODUCTION: Caffeine is a widely consumed psychoactive compound that can cause anxiety and sleep difficulties, in part due to genetic variation. We investigated the association between caffeine consumption, psychological distress, and sleep difficulties in a genetically informative cohort of individuals with a history of depression. METHODS: Survey data and genetic information were sourced from the Australian Genetics of Depression Study (AGDS [n = 20,689, %(female) = 75%, mean age = 43 ± 15 years]). Associations between caffeine consumption and symptoms of distress and sleep disturbance, as well as 9 genetic variants associated with caffeine consumption behaviour, were assessed using linear regression. RESULTS: The highest consumers of caffeine reported higher psychological distress measured by the Kessler 10 scale (β = 1.21, SE = 0.25, p = 1.4 × 10(-6)) compared to the lowest consumers. Consumption was associated with 2 genetic variants with effect sizes ∼0.35 additional caffeinated drinks/day between opposite homozygotes (p < 0.005). A deletion near MMS22L/POU3F2 was associated with 10% increased odds of reporting caffeine susceptibility (OR = 1.1 per deletion [95% CI: 1.04-1.17], p = 0.002). CONCLUSIONS: Higher rates of caffeine consumption were associated with higher levels of psychological distress, but not insomnia, in individuals with a history of depression. While the direction of causality is unclear, caffeine consumption may be a modifiable factor to reduce distress in individuals susceptible to mental health problems. Some of the previous findings of common variant associations with caffeine consumption and susceptibility were replicated.