Psychoses of Epilepsy: Unravelling the Phenotypic and Genotypic Features

IF 7.7 1区医学 Q1 CLINICAL NEUROLOGY Annals of Neurology Pub Date : 2025-02-14 DOI:10.1002/ana.27209

Genevieve Rayner MPsych, PhD, Eliza Honybun MPsych, Melanie Bahlo BSc (Hons), PhD, Karen L. Oliver PhD, Ingrid E. Scheffer MBBS, PhD, FRS

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Abstract

Objectives

We analyzed the genotypic and phenotypic features of patients with psychosis of epilepsy (POE).

Methods

Patients 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.

Results

One 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.

Interpretation

Interictal 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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癫痫精神病：揭示表型和基因型特征。

目的：分析癫痫性精神病（POE）患者的基因型和表型特征。方法：癫痫遗传学研究项目招募的POE患者进行表型和遗传分析。后者包括筛查癫痫基因中的罕见致病变异，以及计算与精神分裂症相关的常见风险变异的多基因风险评分（PRS）。结果：共鉴定出122例POE患者。122人中有86人（70%）患有间歇期精神病，其中精神分裂症是最常见的间歇期表型（36/ 86,42 %）。122例患者中有28例（23%）为后发性精神病，2例（2%）为抗癫痫药物性精神病，6例（5%）为药物性精神病。局灶性癫痫与PIP的相关性（24/ 28,86%）高于间歇性精神病(39/ 86,45%；p解释：间期POE的发生率是PIP的三倍，更可能与癫痫的罕见致病变异和精神分裂症的常见危险变异相关。区分不同的POE表型可以提高临床实践和我们对病因的理解，为精准医疗铺平道路。Ann neurol 2025。

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来源期刊

Annals of Neurology 医学-临床神经学

CiteScore

18.00

自引率

1.80%

发文量

270

审稿时长

3-8 weeks

期刊介绍： Annals of Neurology publishes original articles with potential for high impact in understanding the pathogenesis, clinical and laboratory features, diagnosis, treatment, outcomes and science underlying diseases of the human nervous system. Articles should ideally be of broad interest to the academic neurological community rather than solely to subspecialists in a particular field. Studies involving experimental model system, including those in cell and organ cultures and animals, of direct translational relevance to the understanding of neurological disease are also encouraged.