Postictal psychosis in epilepsy: a clinicogenetic study
Objective: Psychoses affecting people with epilepsy increase disease burden and diminish quality of life. We characterized postictal psychosis, which comprises about one quarter of epilepsy-related psychoses, and has unknown causation.
Methods: We conducted a case-control cohort study including patients diagnosed with postictal 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 postictal 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 postictal psychosis; univariate associations with a p value < 0.20 were used to build a multivariate model. Polygenic risk scores for schizophrenia were calculated.
Results: Cases were more likely to have seizure clustering (odds ratio [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 antiseizure treatment between cases and controls. Polygenic risk scores for schizophrenia in an extended cohort of postictal psychosis cases (n = 58) were significantly higher than in 1,366 epilepsy controls (R2 = 3%, p = 6 × 10-3 ), but not significantly different from 945 independent patients with schizophrenia (R2 = 0.1%, p = 0.775).
Interpretation: Postictal 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 (postictal psychosis) in a common disease.
UK Department of Health's NIHR Biomedical Research Centres funding scheme
Muir Maxwell Trust and the Epilepsy Society
Union Chimique Belge (UCB)
Science Foundation Ireland (16/RC/3948)
European Regional Development Fund
European Commission grant 279062, EpiPGX
NIHR Academic Clinical Fellowship
Chinese Scholarships Council
Mental Health Research UK John Grace QC award 2018
BMA Margaret Temple Fellowship
Medical Research Council (G0901310, G1100583, G1100583)
Wellcome Trust (085475/B/08/Z, 085475/Z/08/Z)
National Human Genome Research Institute (NHGRI)
National Heart, Lung, and Blood Institute
NHGRI grant UM1 HG008895
NHGRI grant 5U01HG009088-02
FutureNeuro industry partners
Open Access Funding provided by Universita degli Studi di Firenze within the CRUI-CARE Agreement
CommentsThe original article is available at https://onlinelibrary.wiley.com/
Published CitationBraatz V. et al. Postictal psychosis in epilepsy: a clinicogenetic study. Ann Neurol. 2021;90(3):464-476.
Publication Date20 July 2021
- Beaumont Hospital
- FutureNeuro Centre
- School of Pharmacy and Biomolecular Sciences
- Neurological and Psychiatric Disorders
- Published Version (Version of Record)