Interaction between sex and early-life stress: influence on epileptogenesis and epilepsy comorbidities

Epilepsy is a common brain disorder which is characterised by recurring seizures. In addition to suffering from the constant stress of living with this neurological condition, patients also frequently experience comorbid psychiatric and cognitive disorders which significantly impact their quality of life. There is growing appreciation that stress, in particular occurring in early life, can negatively impact brain development, creating an enduring vulnerability to develop epilepsy. This aligns with the solid connections between early life environments and the development of psychiatric conditions, promoting the possibility that adverse early life events could represent a common risk factor for the later development of both epilepsy and comorbid psychiatric disorders. The influence of sex has been little studied, but recent research points to potential important interactions, particularly with regard to effects mediated by HPA axis programming. Understanding these interactions, and the underlying molecular mechanisms, will provide important new insights into the causation of both epilepsy and of psychiatric disorders, and potentially open up novel avenues for treatment.