Psychiatric comorbidities in epilepsy: population co-occurrence, genetic correlations and causal effects

Viktor H Ahlqvist; Christina Dardani; Paul Madley-Dowd; Harriet Forbes; Jessica Rast; Caichen Zhong; Renee M Gardner; Christina Dalman; Kristen Lyall; Craig Newschaffer; Torbjörn Tomson; Michael Lundberg; Daniel Berglind; Neil M Davies; Brian K Lee; Cecilia Magnusson; Dheeraj Rai

doi:10.1136/gpsych-2023-101201

Psychiatric comorbidities in epilepsy: population co-occurrence, genetic correlations and causal effects

Gen Psychiatr. 2024 Jan 30;37(1):e101201. doi: 10.1136/gpsych-2023-101201. eCollection 2024.

Authors

Viktor H Ahlqvist^{1

2}, Christina Dardani^{2

3}, Paul Madley-Dowd^{2

3}, Harriet Forbes^{3

4}, Jessica Rast^{5

6}, Caichen Zhong^{5

6}, Renee M Gardner¹, Christina Dalman¹, Kristen Lyall⁵, Craig Newschaffer⁷, Torbjörn Tomson⁸, Michael Lundberg¹, Daniel Berglind^{1

9}, Neil M Davies^{10

11

12}, Brian K Lee^{1

5

6}, Cecilia Magnusson^{1

9}, Dheeraj Rai^{2

3

13

14}

Affiliations

¹ Department of Global Public Health, Karolinska Institutet, Stockholm, Sweden.
² Medical Research Council Integrative Epidemiology Unit, Bristol Medical School, University of Bristol, Bristol, UK.
³ Centre for Academic Mental Health, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
⁴ Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK.
⁵ A.J. Drexel Autism Institute, Drexel University, Philadelphia, PA, USA.
⁶ Department of Epidemiology and Biostatistics, School of Public Health, Drexel University, Philadelphia, PA, USA.
⁷ College of Health and Human Development, Pennsylvania State University, State College, PA, USA.
⁸ Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
⁹ Centre for Epidemiology and Community Medicine, Region Stockholm, Stockholm, Sweden.
¹⁰ K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Norwegian University of Science and Technology, Trondheim, Norway.
¹¹ Division of Psychiatry, University College London, London, UK.
¹² Department of Statistical Sciences, University College London, London, UK.
¹³ NIHR Biomedical Research Centre, University of Bristol, Bristol, UK.
¹⁴ Avon and Wiltshire Partnership, NHS Mental Health Trust, Bristol, UK.

Abstract

Background: Psychiatric comorbidities are common in patients with epilepsy. Reasons for the co-occurrence of psychiatric conditions and epilepsy remain poorly understood.

Aim: We aimed to triangulate the relationship between epilepsy and psychiatric conditions to determine the extent and possible origins of these conditions.

Methods: 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.

Results: 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_g=0.18, 95% CI 0.09 to 0.27, p<0.001)-a correlation that was more pronounced in focal epilepsy (r_g=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.

Conclusions: 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.

Keywords: neuropsychiatry; psychiatry.

Grants and funding

MR/S003940/1/MRC_/Medical Research Council/United Kingdom