Postictal Psychosis in Epilepsy: A Clinicogenetic Study

Vera Braatz; Helena Martins Custodio; Costin Leu; Luigi Agrò; Baihan Wang; Stella Calafato; Genevieve Rayner; Michael G Doyle; Christian Hengsbach; Francesca Bisulli; Yvonne G Weber; Antonio Gambardella; Norman Delanty; Gianpiero Cavalleri; Jacqueline Foong; Ingrid E Scheffer; Samuel F Berkovic; Elvira Bramon; Simona Balestrini; Sanjay M Sisodiya

doi:10.1002/ana.26174

Postictal Psychosis in Epilepsy: A Clinicogenetic Study

Ann Neurol. 2021 Sep;90(3):464-476. doi: 10.1002/ana.26174. Epub 2021 Aug 3.

Authors

Vera Braatz^#^{1

2}, Helena Martins Custodio^#^{2

3}, Costin Leu^{2

4

5}, Luigi Agrò^{2

3}, Baihan Wang⁶, Stella Calafato⁶, Genevieve Rayner^{7

8}, Michael G Doyle^{9

10}, Christian Hengsbach¹¹, Francesca Bisulli^{12

13}, Yvonne G Weber^{11

14}, Antonio Gambardella¹⁵, Norman Delanty^{9

10

16}, Gianpiero Cavalleri^{10

17}, Jacqueline Foong², Ingrid E Scheffer¹⁸, Samuel F Berkovic¹⁹, Elvira Bramon^{6

20

21}, Simona Balestrini^#^{2

3

22}, Sanjay M Sisodiya^#^{2

3}

Affiliations

¹ Department of Neurology, Neurological and Neurosurgical Clinic of Joinville, Joinville, Brazil.
² Department of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, London, UK.
³ Chalfont Centre for Epilepsy, Buckinghamshire, UK.
⁴ Genomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, OH.
⁵ Stanley Center of Psychiatric Research, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA.
⁶ Mental Health Neuroscience Research Department, Division of Psychiatry, University College London, London, UK.
⁷ Melbourne School of Psychological Sciences, University of Melbourne, Parkville, Victoria, Australia.
⁸ Department of Clinical Neuropsychology, Austin Health, Melbourne, Victoria, Australia.
⁹ Epilepsy Programme, Department of Neurology, Beaumont Hospital, Dublin, Ireland.
¹⁰ FutureNeuro Research Centre, Royal College of Surgeons in Ireland, Dublin, Ireland.
¹¹ Department of Neurology and Epileptology, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.
¹² IRCCS Istituto delle Scienze Neurologiche di Bologna, Full Member of the ERN EpiCARE, delle Scienze Neurologiche di Bologna (EpiCARE reference center), Bologna, Italy.
¹³ Dipartimento di Scienze Biomediche e Neuromotorie, Università di Bologna, Bologna, Italy.
¹⁴ Department of Epileptology and Neurology, University of Aachen, Aachen, Germany.
¹⁵ Department of Medical and Surgical Sciences, Institute of Neurology, University Magna Graecia, Catanzaro, Italy.
¹⁶ School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons in Ireland, Dublin, Ireland.
¹⁷ Department of Molecular and Cellular Therapeutics and FutureNeuro Research Centre, Royal College of Surgeons in Ireland, Dublin, Ireland.
¹⁸ University of Melbourne, Austin Health, and Royal Children's Hospital, Florey Institute and Murdoch Children's Research Institute, Melbourne, Victoria, Australia.
¹⁹ Epilepsy Research Centre, Department of Medicine, Austin Health, University of Melbourne, Melbourne, Victoria, Australia.
²⁰ Institute of Psychiatry, Psychology, & Neuroscience at King's College London, London, UK.
²¹ Institute of Cognitive Neuroscience, University College London, London, UK.
²² Neuroscience Department, Children's Hospital 'Anna Meyer'-University of Florence, Florence, Italy.

^# Contributed equally.

Abstract

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. ANN NEUROL 2021;90:464-476.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Case-Control Studies
Cohort Studies
Electroencephalography / methods
Epilepsy / complications
Epilepsy / genetics*
Epilepsy / physiopathology*
Female
Humans
Male
Middle Aged
Polymorphism, Single Nucleotide / genetics*
Psychotic Disorders / etiology
Psychotic Disorders / genetics*
Psychotic Disorders / physiopathology*
Retrospective Studies

Abstract

Publication types

MeSH terms

Grants and funding