Ahlqvist Viktor H, Dardani Christina, Madley-Dowd Paul, Forbes Harriet, Rast Jessica, Zhong Caichen, Gardner Renee M, Dalman Christina, Lyall Kristen, Newschaffer Craig, Tomson Torbjörn, Lundberg Michael, Berglind Daniel, Davies Neil M, Lee Brian K, Magnusson Cecilia, Rai Dheeraj
Department of Global Public Health, Karolinska Institutet, Stockholm, Sweden.
Medical Research Council Integrative Epidemiology Unit, Bristol Medical School, University of Bristol, Bristol, UK.
Gen Psychiatr. 2024 Jan 30;37(1):e101201. doi: 10.1136/gpsych-2023-101201. eCollection 2024.
Psychiatric comorbidities are common in patients with epilepsy. Reasons for the co-occurrence of psychiatric conditions and epilepsy remain poorly understood.
We aimed to triangulate the relationship between epilepsy and psychiatric conditions to determine the extent and possible origins of these conditions.
Using nationwide Swedish health registries, we quantified the lifetime prevalence of psychiatric disorders in patients with epilepsy. We then used summary data from genome-wide association studies to investigate whether the identified observational associations could be attributed to a shared underlying genetic aetiology using cross-trait linkage disequilibrium score regression. Finally, we assessed the potential bidirectional relationships using two-sample Mendelian randomisation.
In a cohort of 7 628 495 individuals, we found that almost half of the 94 435 individuals diagnosed with epilepsy were also diagnosed with a psychiatric condition in their lifetime (adjusted lifetime prevalence, 44.09%; 95% confidence interval (CI) 43.78% to 44.39%). We found evidence for a genetic correlation between epilepsy and some neurodevelopmental and psychiatric conditions. For example, we observed a genetic correlation between epilepsy and attention-deficit/hyperactivity disorder (r=0.18, 95% CI 0.09 to 0.27, p<0.001)-a correlation that was more pronounced in focal epilepsy (r=0.23, 95% CI 0.09 to 0.36, p<0.001). Findings from Mendelian randomisation using common genetic variants did not support bidirectional effects between epilepsy and neurodevelopmental or psychiatric conditions.
Psychiatric comorbidities are common in patients with epilepsy. Genetic correlations may partially explain some comorbidities; however, there is little evidence of a bidirectional relationship between the genetic liability of epilepsy and psychiatric conditions. These findings highlight the need to understand the role of environmental factors or rare genetic variations in the origins of psychiatric comorbidities in epilepsy.
精神疾病合并症在癫痫患者中很常见。精神疾病与癫痫同时出现的原因仍知之甚少。
我们旨在梳理癫痫与精神疾病之间的关系，以确定这些疾病的程度和可能的根源。
利用瑞典全国性健康登记系统，我们对癫痫患者中精神疾病的终生患病率进行了量化。然后，我们使用全基因组关联研究的汇总数据，通过跨性状连锁不平衡评分回归来研究已确定的观察性关联是否可归因于共同的潜在遗传病因。最后，我们使用两样本孟德尔随机化评估了潜在的双向关系。
在一个由7628495人组成的队列中，我们发现，在94435名被诊断患有癫痫的个体中，几乎有一半在其一生中也被诊断患有精神疾病（调整后的终生患病率为44.09%；95%置信区间（CI）为43.78%至44.39%）。我们发现癫痫与一些神经发育和精神疾病之间存在遗传相关性的证据。例如，我们观察到癫痫与注意力缺陷多动障碍之间存在遗传相关性（r=0.18，95%CI为0.09至0.27，p<0.001）——这种相关性在局灶性癫痫中更为明显（r=0.23，95%CI为0.09至0.36，p<0.001）。使用常见基因变异进行的孟德尔随机化研究结果不支持癫痫与神经发育或精神疾病之间存在双向影响。
精神疾病合并症在癫痫患者中很常见。遗传相关性可能部分解释了一些合并症；然而，几乎没有证据表明癫痫的遗传易感性与精神疾病之间存在双向关系。这些发现凸显了了解环境因素或罕见基因变异在癫痫患者精神疾病合并症发病根源中所起作用的必要性。
