ArticleAnnals of neurology2025
Psychoses of Epilepsy: Unravelling the Phenotypic and Genotypic Features.
Article in Annals of neurology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
objectivesWe analyzed the genotypic and phenotypic features of patients with psychosis of epilepsy (POE).
methodsPatients with POE recruited to an epilepsy genetics research program underwent phenotyping and genetic analysis. The latter included screening for rare pathogenic variants in epilepsy genes, and polygenic risk score (PRS) calculation for common risk variants associated with schizophrenia.
resultsOne hundred twenty-two individuals with POE were identified. Eighty-six of 122 of the individuals (70%) had interictal psychosis, with schizophrenia the most common interictal phenotype (36/86, 42%). Twenty-eight of 122 of the individuals (23%) had postictal psychosis (PIP), 2 of 122 of the individuals (2%) had antiseizure medication-induced psychosis, and 6 of 122 of the individuals (5%) had substance-induced psychosis. Focal epilepsies were more frequently associated with PIP (24/28, 86%) compared to interictal psychosis (39/86, 45%; p < 0.05). Twenty-nine percent of the patients with POE with genetic data had a rare pathogenic variant: 19 in an epilepsy gene (PCDH19, SCN1A, DEPDC5, KCNT1, CHD2, SLC2A1, NPRL3, CLN3, NPRL3, ATP1A3, and CACNA1A) and 4 had a chromosomal anomaly. Fifty-seven percent of the patients with a rare pathogenic variant had interictal schizophrenia/schizophreniform disorder rather than PIP (9%; p < 0.05). PRSs showed that schizophrenia-related common risk variants were enriched in patients with POE compared to population controls (p = 0.0007), however, among the POE phenotypes, a raised PRS was only observed in interictal schizophrenia (p = 0.015) and not in those with PIP or other interictal POEs.
interpretationInterictal POE is threefold more common than PIP, and more likely to be associated with both rare pathogenic variants for epilepsy and common risk variants for schizophrenia. Distinguishing between different POE phenotypes enhances clinical practice and our understanding of etiology, paving the way for precision medicine. ANN NEUROL 2025;98:35-47.
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