The Diathesis-Epilepsy Model: How Past Events Impact the Development of Epilepsy and Comorbidities.

In epilepsy, seizures and comorbidities (e.g., cognitive deficits and depression) occur when specific thresholds are crossed. These thresholds depend on the diathesis (or vulnerability) of a given individual. The diathesis is controlled by multiple genetic and environmental factors. Diathesis changes over multiple timescales: on a daily basis, and as part of the development/aging processes, etc. The diathesis-epilepsy model introduced here provides a conceptual framework to understand how past events (e.g., a very stressful event) can directly influence the occurrence of epilepsy and comorbidities later in life. Experimental evidence supports this model, and the existence of biomarkers predictive of a vulnerability state have led to the development of preventive therapeutic strategies. Epigenetic modifications could be a key determinant of diathesis. Their role is discussed.