Neuroinflammation as a shared mechanism linking epilepsy and psychiatric comorbidities

Although epilepsy arises from diverse etiologies, neuroinflammatory processes have emerged as a key factor in epileptogenesis. Neuroinflammation activates a complex network of cellular and molecular mechanisms involving microglia and astrocytes, aswell as the production of pro-inflammatory mediators such as interleukin IL-1β, IL-6, and TNF-α, with inflammasome signaling representing a major upstream driver of these responses. These inflammatory processes contribute to increased seizure susceptibility and facilitate seizure propagation. Beyond their role in seizure generation, inflammatory mechanisms have also been implicated in the development of psychiatric disorders commonly associated with epilepsy. Depression, anxiety, and psychotic disorders occur at disproportionately high rates in people with epilepsy, particularly in those with temporal lobe epilepsy. Notably, many of these psychiatric conditions are associated with inflammatory alterations. This convergence suggests that neuroinflammatory signaling may represent a shared pathophysiological mechanism linking epileptic network dysfunction and psychiatric symptomatology. In this review, we synthesize clinical and experimental evidence supporting the involvement of inflammatory pathways in both epilepsy and its major psychiatric comorbidities. We discuss the molecular mediators, cellular mechanisms, and neural circuit alterations that may underlie this association and evaluate their potential utility as biomarkers andtherapeutic targets for improving neuropsychiatric outcomes in epilepsy.

Keywords: Neuroinflammation; Seizure; Epilepsy; Depression; Anxiety; Psychosis.