Theory of mind: A cognitive endophenotype of juvenile myoclonic epilepsy?

Juvenile myoclonic epilepsy (JME), the most common idiopathic generalized epilepsy, is associated with neuropsychological and psychiatric comorbidities, including social cognition and theory of mind (ToM) deficits. The interplay between clinical features, social cognition, and their neural and genetic substrates remains poorly understood. We investigated social cognition in individuals with JME and their unaffected siblings to explore its potential as a disease endophenotype.

In this prospective cross-sectional study, 52 individuals with JME (age = 29 ± 11 years, 56% female), 13 unaffected siblings (age = 26 ± 7 years, 38% female), and 64 healthy controls (age = 28 ± 11 years, 55% female) completed neuropsychological tests and self-report questionnaires assessing social cognition. Test scores were assigned to previously defined theoretical social cognition domains and averaged into domain-specific composite z-scores. Participants underwent functional magnetic resonance imaging using a ToM paradigm. Social cognition performance was compared between groups, and associations with clinical variables were explored.

Compared with healthy controls, individuals with JME showed reduced performance in tasks requiring mentalizing about beliefs (e.g., Faux Pas Test, Reading the Mind in the Eyes Test). Domain-level analyses confirmed selective impairment in mentalizing about beliefs, whereas other ToM components showed no consistent group differences. Unaffected siblings did not differ significantly from either individuals with JME or healthy controls on any measure.

Our study aligns with previous literature expanding the extent of ToM impairment in individuals with JME. An endophenotypic role of ToM in JME could not be established in the present sample and remains a hypothesis to be tested in adequately powered studies.