Network Dysfunction in Comorbid Psychiatric Illnesses and Epilepsy

The episodic nature of both epilepsy and psychiatric illnesses suggests that the brain switches between healthy and pathological states. The most obvious example of transitions between network states related to epilepsy is the manifestation of ictal events. In addition to seizures, there are more subtle changes in network communication within and between brain regions, which we propose may contribute to psychiatric illnesses associated with the epilepsies. This review will highlight evidence supporting aberrant network activity associated with epilepsy and the contribution to cognitive impairments and comorbid psychiatric illnesses. Further, we discuss potential mechanisms mediating the network dysfunction associated with comorbidities in epilepsy, including interneuron loss and hypothalamic-pituitary-adrenal axis dysfunction. Conceptually, it is necessary to think beyond ictal activity to appreciate the breadth of network dysfunction contributing to the spectrum of symptoms associated with epilepsy, including psychiatric comorbidities.