Advances in cognitive, behavioral, and psychiatric changes in epilepsy: mechanisms and interventions

Epilepsy, one of the most common neurological disorders, affects over 70 million people worldwide, with more than 80% living in developing countries, where the estimated prevalence is at least twice that reported in developed nations. Many patients experience a wide range of neuropsychological and psychiatric comorbidities, including social dysfunction, which can negatively affect their quality of life, reduce life expectancy, increase healthcare utilization, and elevate medical costs. Cognitive and psychiatric changes in epilepsy are often linked to dysfunction in specific brain regions, including the hippocampus, amygdala, prefrontal cortex, and temporal lobe structures, which play key roles in learning, memory, emotion, and social behavior. To investigate the mechanisms underlying these comorbidities, preclinical studies often rely on rodent models of epilepsy. Chemoconvulsant-induced temporal lobe epilepsy and electrical kindling produce chronic seizures accompanied by deficits in learning, memory, and emotional behaviors. Early-life tetrodotoxin exposure and post-traumatic models reveal long-term effects on cognition and social-emotional functioning, while genetic models (e.g., GAERS, WAG/Rij rats, SCN1A mutant mice) exhibit cognitive impairments alongside anxiety-, depression-, or autistic-like traits. Other mammalian models, including dogs, cats, pigs, and non-human primates, are also used for translational studies of seizures, cognition, and behavioral comorbidities. Whether involving chemically, electrically induced, or naturally occurring seizures, these models are crucial for linking mechanistic insights to cognitive, emotional, and psychiatric manifestations, guiding the development of targeted interventions. Although social cognitive deficits and psychiatric comorbidities are not evident in all individuals with epilepsy, when present they can reduce social engagement and hinder the formation of satisfying interpersonal relationships. Consequently, these patients often receive less social support and are more likely to remain single or unemployed.

This Research Topic aims to highlight recent advances in understanding the mechanisms under-lying cognitive and psychiatric alterations in epilepsy, as well as the development of effective interventions. Despite significant progress, many aspects of social dysfunction, cognitive im-pairment, and psychiatric comorbidities remain poorly understood, including their relationship with epilepsy onset, seizure control, and antiseizure medications. By integrating evidence from both clinical studies and animal models, this Research Topic seeks to unravel these complex processes, foster new therapeutic strategies, and ultimately enhance the quality of life and long-term outcomes for individuals living with epilepsy.

• Mechanisms underlying cognitive and psychiatric alterations in epilepsy
• Interactions between epilepsy onset, seizure control, antiseizure medications, and neurocognitive outcomes
• Social dysfunction and its neural or behavioral correlates
• Comparative evidence from animal models and clinical populations
• Interventions beyond seizure control, targeting the broader effects of recurrent seizures and promoting systemic, integrative improvements
• Translational approaches linking basic mechanisms to clinical practice
• Novel methodologies for assessing cognition, or psychiatric comorbidities in epilepsy