Stress and HPA axis dysfunction impact diverse epilepsy outcomes including psychiatric comorbidities and SUDEP

Epilepsy is a chronic neurological disorder characterized by recurrent, spontaneous seizures. In addition to seizures, patients experience additional adverse outcomes, including increased risk of psychiatric comorbidities and premature mortality. Stress is the most commonly reported trigger for seizures and particularly severe or chronic stress has been linked to the development of epilepsy itself. Stress has also been found to worsen psychiatric illness and is a risk factor for sudden death in individuals with and without epilepsy. The body's response to stress is coordinated by the hypothalamic-pituitary-adrenal (HPA) axis. Perturbations in stress hormone levels and their receptors are associated with psychiatric illness as well as sudden unexpected death in epilepsy (SUDEP), which is the leading cause of death in patients with refractory epilepsy. This review examines our present understanding of the relationship between stress, HPA axis dysfunction, and epilepsy sequela. We highlight stress and HPA axis dysfunction as salient risk factors for epilepsy patients that may directly contribute to their prognoses. A better understanding of how stress facilitates deleterious outcomes in epilepsy will inform interventions to improve the quality of life and increase longevity in people with epilepsy.