Objective: To investigate the risk of autism spectrum disorder (ASD) in individuals with epilepsy and in their first-degree relatives to determine shared etiology.Methods: Through the Swedish Patient Register, we identified 85,201 individuals with epilepsy, as well as all their siblings (n 5 80,511) and offspring (n 5 98,534). Each individual with epilepsy was compared with 5 controls, matched for age, sex, calendar period, and county, while siblings and offspring were compared with siblings and offspring of controls. We excluded siblings and offspring with epilepsy. Using Cox regression, we calculated hazard ratios (HRs) for future diagnosis of ASD. Logistic regression was applied to calculate odds ratios (ORs) for prior diagnosis of ASD.Results: During follow-up, 1,381 (1.6%) individuals with epilepsy and 700 (0.2%) controls were diagnosed with ASD. Individuals with epilepsy were therefore at increased risk of future ASD (HR 10.49, 95% confidence interval [CI] 9.55-11.53), with the highest risk seen in individuals diagnosed with epilepsy in childhood. Both siblings (HR 1.62, 95% CI 1.43-1.83) and offspring (HR 1.64, 95% CI 1.46-1.84) of epilepsy patients were at increased risk of ASD. The risk in the offspring was particularly high in mothers with epilepsy (HR 1.91; 95% CI 1.63-2.23). Epilepsy was also associated with a prior diagnosis of ASD (OR 4.56, 95% CI 4.02-5.18). According to the definition of the International League Against Epilepsy, "epilepsy is a disorder of the brain characterized by an enduring predisposition to generate epileptic seizures and by the neurobiologic, cognitive, psychological, and social consequences of this condition."
Conclusions:1 Epilepsy frequently co-occurs with psychiatric disturbances, such as mood and anxiety disorders and autism spectrum disorder (ASD). 1 ASD is a neurodevelopmental disorder characterized by impairment in social interaction and communication and restricted, repetitive, or stereotypic behavior, interests, and activities. The strength and nature of the association between epilepsy and ASD have been scarce and difficult to interpret. A US study of health care data, a British psychiatric morbidity survey, and a prospective screening study all found that ASD as a comorbidity in patients with epilepsy had a prevalence between 1.3% and 21% and an odds ratio (OR) between 6 and 22.