Can we and should we use animal models to study neurobehavioral comorbidities of epilepsy?

Animal systems have been widely used to examine mechanisms of neurobehavioral comorbidities of epilepsy and to help in developing their effective therapies. Despite the progress made in the field, animal studies have their limitations stemming both from issues with modeling neuropsychiatric disorders in the laboratory and from drawbacks of animal models of epilepsy themselves. This review discusses advantages and weaknesses of experimental paradigms and approaches used to model and to analyze neurobehavioral comorbidities of epilepsy, from the perspectives of their needs, interpretation, ways of improvement, and clinical relevance. Developmental studies are required to adequately address age-specific aspects of the comorbidities. The deployment of preclinical Common Data Elements (pCDEs) for epilepsy research should facilitate the standardization and the harmonization of studies in question, while the application of Research Domain Criteria (RDoC) to characterize neurobehavioral disorders in animals with epilepsy should help in closing the bench-to-bedside gap. Special Issue: Epilepsy & Behavior's 20th Anniversary.