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

Postictal Psychosis in Epilepsy: A Clinicogenetic Study

Vera Braatz #  1   2 , Helena Martins Custodio #  2   3 , Costin Leu  2   4   5 , Luigi Agrò  2   3 , Baihan Wang  6 , Stella Calafato  6 , Genevieve Rayner  7   8 , Michael G Doyle  9   10 , Christian Hengsbach  11 , Francesca Bisulli  12   13 , Yvonne G Weber  11   14 , Antonio Gambardella  15 , Norman Delanty  9   10   16 , Gianpiero Cavalleri  10   17 , Jacqueline Foong  2 , Ingrid E Scheffer  18 , Samuel F Berkovic  19 , Elvira Bramon  6   20   21 , Simona Balestrini #  2   3   22 , Sanjay M Sisodiya #  2   3
Affiliations

Postictal Psychosis in Epilepsy: A Clinicogenetic Study

Vera Braatz et al. Ann Neurol. 2021 Sep.

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.

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Conflict of interest statement

Nothing to report.

Figures

FIGURE 1
FIGURE 1
Flow chart of the study design.
FIGURE 2
FIGURE 2
Bar plot displaying the model fit of the schizophrenia (SCZ) polygenic risk score (PRS) at different p value thresholds in the following models: (A) postictal psychosis (PIP) and SCZ samples versus epilepsy controls, (B) PIP versus epilepsy controls, (C) SCZ versus PIP, and (D) SCZ versus epilepsy controls.
FIGURE 3
FIGURE 3
Genome‐wide schizophrenia (SCZ) polygenic risk score (PRS). (A) SCZ‐PRS estimation for postictal psychosis (PIP) and SCZ controls versus epilepsy controls (controls) for p value threshold = 10−1. (B) SCZ‐PRS estimation for PIP versus epilepsy controls. (C) SCZ‐PRS estimation for SCZ versus PIP. (D) SCZ‐PRS estimation for SCZ versus epilepsy controls.
FIGURE 4
FIGURE 4
(A) Schizophrenia (SCZ) polygenic risk score (PRS) in patients with single episodes of postictal psychosis (PIP) compared to values in patients with recurrent episodes and those who went on to develop chronic psychosis. (B) SCZ‐ PRS in patients with PIP with or without a family history of psychiatric disease.
See this image and copyright information in PMC

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