Annals of Neurology

Post-ictal psychosis in epilepsy: A clinico-genetic study

2 August, 2021

Braatz, V., Martins Custodio, H., Leu, C., Agro, L., Wang, B., Calafato, S., Rayner, G., Doyle, M.G., Hengsbach, C., Bisulli, F., Weber, Y.G., Gambardella, A., Delanty, N., Cavalleri, G., Foong, J., Scheffer, I.E., Berkovic, S.F., Bramon, E., Balestrini, S. and Sisodiya, S.M.

Annals of Neurology 20 July 2021 Accepted Author Manuscript.


Psychoses affecting people with epilepsy increase disease burden and diminish quality of life. We characterised post-ictal psychosis, which comprises about one-quarter of epilepsy-related psychoses, and has unknown causation.


We conducted a case-control cohort study including patients diagnosed with post-ictal psychosis, confirmed by psychiatric assessment, with available data regarding epilepsy, treatment, psychiatric history, psychosis profile and outcomes. After screening 3,288 epilepsy patients, we identified 83 with psychosis: 49 had post-ictal psychosis. Controls were 98 adults, matched by age and epilepsy type, with no history of psychosis. Logistic regression was used to investigate clinical factors associated with post-ictal psychosis; univariate associations with a P-value


Cases were more likely to have seizure clustering (OR 7.59, P<0.001), seizures with a recollected aura (OR 2.49, P=0.013) and a family history of psychiatric disease (OR 5.17, P=0.022). Cases showed predominance of right temporal epileptiform discharges (OR 4.87, P=0.007). There was no difference in epilepsy duration, neuroimaging findings or anti-seizure treatment between cases and controls. Polygenic risk scores for schizophrenia in an extended cohort of post-ictal psychosis cases (58) were significantly higher than in 1,366 epilepsy controls (R2=3%, P=6x10-3), but not significantly different from 945 independent patients with schizophrenia (R2=0.1%, P=0.775).


Post-ictal psychosis occurs under particular circumstances in people with epilepsy with a heightened genetic predisposition to schizophrenia, illustrating how disease biology (seizures) and trait susceptibility (schizophrenia) may interact to produce particular outcomes (post-ictal psychosis) in a common disease.