National Center for Register-Based Research, Aarhus University, Aarhus, Denmark; Centre for Integrated Register-based Research, CIRRAU, Aarhus University, Aarhus, Denmark.
National Center for Register-Based Research, Aarhus University, Aarhus, Denmark; Centre for Integrated Register-based Research, CIRRAU, Aarhus University, Aarhus, Denmark; Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus University, Aarhus, Denmark.
Lancet Child Adolesc Health. 2019 Feb;3(2):99-108. doi: 10.1016/S2352-4642(18)30351-1. Epub 2018 Dec 7.
Paediatric seizures have been linked to psychiatric disorders in childhood, but there is a paucity of large-scale population-based studies of psychiatric comorbidity in later life. We aimed to examine the relation between childhood seizures and the risk of psychiatric disorders in adolescence and early adulthood.
We did a register-based cohort study of all individuals born in Denmark in 1978-2002. Using diagnostic information from the Danish National Patient Register, all cohort members were categorised according to occurrence of febrile seizures and epilepsy, before entering the follow-up period on their 10th birthday. Individuals were followed up until onset of mental illness, death, emigration, or the end of the study period on Dec 31, 2012. Cox regression analyses were used to estimate the risk of five predefined groups of psychiatric disorders (substance abuse disorders, schizophrenia, mood disorder, anxiety, and personality disorder), separately and combined. Models were adjusted for relevant confounders.
Between Jan 1, 1978, and Dec 31, 2002, 1 291 679 individuals were born in Denmark and followed up in our population cohort (approximately 15 million person-years). 43 148 individuals had a history of febrile seizures, 10 355 had epilepsy, and 1696 had both these disorders. 83 735 (6%) cohort members were identified with at least one of the psychiatric disorders of interest. The risk of any psychiatric disorder was raised in individuals with a history of febrile seizures (hazard ratio [HR] 1·12, 95% CI 1·08-1·17), epilepsy (1·34, 1·25-1·44), or both disorders (1·50, 1·28-1·75). Excess risk of psychiatric illness associated with childhood seizures was present across a range of different disorders, most notably schizophrenia but also anxiety and mood disorders. Associations did not differ between males and females (p=0·30) but increased with a growing number of admissions for febrile seizures (p<0·0001) and with later onset of childhood epilepsy (p<0·0001).
Children with epilepsy and febrile seizures-with and without concomitant epilepsy-are at increased risk of developing a broad range of psychiatric disorders in later life. Clarification of the underlying mechanisms attributable to these associations is needed to identify potential options for prevention.
Novo Nordisk Foundation, Danish Epilepsy Association, Central Denmark Region, Lundbeck Foundation, and Stanley Medical Research Institute.
小儿癫痫与儿童期精神障碍有关，但关于癫痫患者在以后生活中合并精神障碍的大规模人群研究较少。本研究旨在探讨儿童期癫痫发作与青少年和成年早期精神障碍风险之间的关系。
我们进行了一项基于登记的队列研究，纳入所有 1978 年至 2002 年期间在丹麦出生的个体。通过丹麦全国患者登记处的诊断信息，所有队列成员在 10 岁生日前根据热性惊厥和癫痫的发生情况进行分类。个体在精神疾病发病、死亡、移民或 2012 年 12 月 31 日研究结束前被随访。使用 Cox 回归分析分别和联合估计五类预先设定的精神障碍（物质滥用障碍、精神分裂症、心境障碍、焦虑症和人格障碍）的风险。模型调整了相关混杂因素。
1978 年 1 月 1 日至 2002 年 12 月 31 日期间，丹麦共有 1291679 人出生，在我们的人群队列中接受随访（约 1500 万人年）。43148 人有热性惊厥史，10355 人患有癫痫，1696 人同时患有这两种疾病。83735 名（6%）队列成员被确定患有至少一种感兴趣的精神障碍。有热性惊厥史（风险比[HR]1.12，95%CI 1.08-1.17）、癫痫（1.34，1.25-1.44）或同时患有这两种疾病（1.50，1.28-1.75）的个体发生任何精神障碍的风险增加。与儿童期癫痫发作相关的精神疾病风险增加见于一系列不同的疾病，最显著的是精神分裂症，但也包括焦虑症和心境障碍。男性和女性之间的相关性没有差异（p=0.30），但随着热性惊厥发作次数的增加（p<0.0001）和儿童期癫痫发作时间的延迟（p<0.0001）而增加。
患有癫痫和热性惊厥的儿童，无论是否伴有癫痫，以后发生一系列广泛的精神障碍的风险均增加。需要阐明这些关联的潜在机制，以确定潜在的预防选择。
诺和诺德基金会、丹麦癫痫协会、丹麦中央大区、伦德贝克基金会和斯坦利医学研究所。
