Stress, epilepsy, and psychiatric comorbidity: how can animal models inform the clinic?

Psychiatric complaints afflict many patients with epilepsy, and these contribute significantly to the impaired quality of life experienced by sufferers of this common group of neurological conditions. Psychiatric disorders in epilepsy patients are under-diagnosed and under-treated. Moreover, evidence suggests that the psychiatric disorders may act as risk factors for some types of epilepsy and exacerbate disease progression in established cases, promoting the case for a bidirectional relationship between epilepsy and psychopathology. While cause and effect relationships can be difficult to establish in human studies, appropriate animal models provide valuable tools with which to study the interactions between epilepsy and stress-related disorders. Indeed, many epilepsy models exhibit behavioral phenotypes which are reflective of psychiatric disorders, and, conversely, stressful environments appear to promote a vulnerability to developing epilepsy. This review summarizes this research area, exploring the behavioral phenotypes in animal models of epilepsy and then examining the influence of stressful environments on susceptibility to seizures and epilepsy. The ultimate goal of this line of research is to be able to translate these findings to humans. Understanding the relationships between epilepsy and associated psychiatric disorders will facilitate effective treatment of mood disorders in epilepsy, inform about the pathophysiology of each individually, and potentially open up novel therapeutic disease-modifying strategies for patients with epilepsy.