Psychiatric comorbidities in epilepsy: population co-occurrence, genetic correlations and causal effects

BackgroundPsychiatric comorbidities are common in patients with epilepsy. Reasons for the co-occurrence of psychiatric conditions and epilepsy remain poorly understood.AimWe aimed to triangulate the relationship between epilepsy and psychiatric conditions to determine the extent and possible origins of these conditions.MethodsUsing nationwide Swedish health registries, we quantified the lifetime prevalence of psychiatric disorders in patients with epilepsy. We then used summary data from genome-wide association studies to investigate whether the identified observational associations could be attributed to a shared underlying genetic aetiology using cross-trait linkage disequilibrium score regression. Finally, we assessed the potential bidirectional relationships using two-sample Mendelian randomisation.ResultsIn a cohort of 7 628 495 individuals, we found that almost half of the 94 435 individuals diagnosed with epilepsy were also diagnosed with a psychiatric condition in their lifetime (adjusted lifetime prevalence, 44.09%; 95% confidence interval (CI) 43.78% to 44.39%). We found evidence for a genetic correlation between epilepsy and some neurodevelopmental and psychiatric conditions. For example, we observed a genetic correlation between epilepsy and attention-deficit/hyperactivity disorder (rg=0.18, 95% CI 0.09 to 0.27, p