Abstract
Background
Epilepsy and attention-deficit/hyperactivity disorder (ADHD) are strongly associated;
however, the underlying factors contributing to their co-occurrence remain unclear.
A shared genetic liability has been proposed as one possible mechanism. Therefore,
our goal in this study was to investigate the familial coaggregation of epilepsy and
ADHD and to estimate the contribution of genetic and environmental risk factors to
their co-occurrence.
Methods
We identified 1,899,654 individuals born between 1987 and 2006 via national Swedish
registers and linked each individual to his or her biological relatives. We used logistic
regression to estimate the association between epilepsy and ADHD within individual
and across relatives. Quantitative genetic modeling was used to decompose the cross-disorder
covariance into genetic and environmental factors.
Results
Individuals with epilepsy had a statistically significant increased risk of ADHD (odds
ratio [OR] = 3.47, 95% confidence interval [CI] = 3.33–3.62). This risk increase extended
to children whose mothers had epilepsy (OR = 1.85, 95% CI = 1.75–1.96), children whose
fathers had epilepsy (OR = 1.64, 95% CI = 1.54–1.74), full siblings (OR = 1.56, 95%
CI = 1.46–1.67), maternal half siblings (OR = 1.28, 95% CI = 1.14–1.43), paternal
half siblings (OR = 1.10, 95% CI = 0.96–1.25), and cousins (OR = 1.15, 95% CI = 1.10–1.20).
The genetic correlation was 0.21 (95% CI = 0.02–0.40) and explained 40% of the phenotypic
correlation between epilepsy and ADHD, with the remaining variance largely explained
by nonshared environmental factors (49%, nonshared environmental correlation = 0.36,
95% CI = 0.23–0.49). The contribution of shared environmental factors to the cross-disorder
overlap was not statistically significant (11%, shared environmental correlation =
0.32, 95% CI = −0.16–0.79).
Conclusions
This study demonstrates a strong and etiologically complex association between epilepsy
and ADHD, with shared familial factors and risk factors unique to the individual contributing
to co-occurrence of the disorders. Our findings suggest that epilepsy and ADHD may
share less genetic risk as compared with other neurodevelopmental disorders.
Keywords
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References
- A national profile of childhood epilepsy and seizure disorder.Pediatrics. 2012; 129: 256-264
- Annual research review: A meta-analysis of the worldwide prevalence of mental disorders in children and adolescents.J Child Psychol Psychiatry. 2015; 56: 345-365
- Comorbidity and childhood epilepsy: A nationwide registry study.Pediatrics. 2016; 138
- Childhood epilepsy, febrile seizures, and subsequent risk of ADHD.Pediatrics. 2016; 138
- Association between attention-deficit/hyperactivity disorder and epilepsy in pediatric populations.Expert Rev Neurother. 2009; 9: 1747-1754
- Epilepsy and attention-deficit hyperactivity disorder: Links, risks, and challenges.Neuropsychiatr Dis Treat. 2016; 12: 287-296
- Correlation between epilepsy and attention deficit hyperactivity disorder: A population-based cohort study.PLoS One. 2013; 8: e57926
- ADHD as a risk factor for incident unprovoked seizures and epilepsy in children.Arch Gen Psychiatry. 2004; 61: 731-736
- The frequency, complications and aetiology of ADHD in new onset paediatric epilepsy.Brain. 2007; 130: 3135-3148
- Reappraisal of abnormal EEG findings in children with ADHD: On the relationship between ADHD and epileptiform discharges.Epilepsy Behav. 2014; 41: 251-256
- Developmental brain dysfunction: Revival and expansion of old concepts based on new genetic evidence.Lancet Neurol. 2013; 12: 406-414
- Familial clustering of epilepsy and behavioral disorders: Evidence for a shared genetic basis.Epilepsia. 2012; 53: 301-307
- Elevated rates of ADHD in mothers of children with comorbid ADHD and epilepsy.Neuropsychiatry (London). 2012; 2: 385-391
- Pre- and perinatal risk factors in adults with attention-deficit/hyperactivity disorder.Biol Psychiatry. 2012; 71: 474-481
- The Swedish personal identity number: Possibilities and pitfalls in healthcare and medical research.Eur J Epidemiol. 2009; 24: 659-667
- The Swedish Medical Birth Registry: A Summary of Content and quality [Report No. 2003-112-3].National Board of Health and Welfare, Stockholm, Sweden2003
- The Swedish Multi-generation Register.Methods Mol Biol. 2011; 675: 215-220
- The ICD-10 Classification of Mental and Behavioural Disorders: Clinical Descriptions and Diagnostic Guidelines.World Health Organization, Geneva, Switzerland1992
- External review and validation of the Swedish National Inpatient Register.BMC Public Health. 2011; 11: 450
- The new Swedish Prescribed Drug Register—Opportunities for pharmacoepidemiological research and experience from the first six months.Pharmacoepidemiol Drug Saf. 2007; 16: 726-735
- Different Families Live in Dfferent Ways—A Survey on Residence and Support of Children After a Separation [Report No. 2014-02-21].Statistics Sweden, Stockholm, Sweden2014
- Familial liability for eating disorders and suicide attempts: Evidence from a population registry in Sweden.JAMA Psychiatry. 2016; 73: 284-291
- Shared familial risk factors between attention-deficit/hyperactivity disorder and overweight/obesity—A population-based familial coaggregation study in Sweden.J Child Psychol Psychiatry. 2017; 58: 711-718
- Methodology for Genetic Studies of Twins and Families.Springer Science & Business Media, New York1992
- Heritability, assortative mating and gender differences in violent crime: Results from a total population sample using twin, adoption, and sibling models.Behav Genet. 2012; 42: 3-18
- The familial co-aggregation of attention-deficit/hyperactivity disorder and intellectual disability: A register-based family study.J Am Acad Child Adolesc Psychiatry. 2017; 56: 167-174.e1
- OpenMx 2.0: Extended structural equation and statistical modeling.Psychometrika. 2016; 81: 535-549
- Bootstrap methods for standard errors, confidence intervals, and other measures of statistical accuracy.Statist Sci. 1986; 1: 54-75
- A structural approach to the familial coaggregation of disorders.Epidemiology. 2008; 19: 431-439
Anttila V, Bulik-Sullivan B, Finucane HK, Bras J, Duncan L, Escott-Price V, et al. (2016): Analysis of shared heritability in common disorders of the brain [published online ahead of print Apr 16]. bioRxiv.
- Epilepsy associated with autism and attention deficit hyperactivity disorder: Is there a genetic link?.Brain Dev. 2014; 36: 185-193
- The genetics of autism spectrum disorders and related neuropsychiatric disorders in childhood.Am J Psychiatry. 2010; 167: 1357-1363
- Evidence for shared genetic influences on self-reported ADHD and autistic symptoms in young adult Australian twins.Twin Res Hum Genet. 2008; 11: 579-585
- Evidence for overlapping genetic influences on autistic and ADHD behaviours in a community twin sample.J Child Psychol Psychiatry. 2008; 49: 535-542
- The familial co-aggregation of ASD and ADHD: A register-based cohort study.Mol Psychiatry. 2017; ([published online ahead of print Feb 28])
- Gestational age, birth weight, intrauterine growth, and the risk of epilepsy.Am J Epidemiol. 2008; 167: 262-270
- Preterm birth and mortality and morbidity: A population-based quasi-experimental study.JAMA Psychiatry. 2013; 70: 1231-1240
- Familial risk of epilepsy: A population-based study.Brain. 2014; 137: 795-805
- The treatment of epilepsy in pregnancy: The neurodevelopmental risks associated with exposure to antiepileptic drugs.Reprod Toxicol. 2016; 64: 203-210
- Complex inheritance and parent-of-origin effect in juvenile myoclonic epilepsy.Brain Dev. 2006; 28: 92-98
- Sociodemographic differences in antiepileptic drug prescriptions to adult epilepsy patients.Neurology. 2010; 74: 295-301
- Cause-specific mortality in epilepsy: A cohort study of more than 9,000 patients once hospitalized for epilepsy.Epilepsia. 1997; 38: 1062-1068
- Familial confounding of the association between maternal smoking during pregnancy and ADHD in offspring.J Child Psychol Psychiatry. 2014; 55: 61-68
- Coffee consumption during pregnancy and the risk of hyperkinetic disorder and ADHD: A prospective cohort study.Acta Paediatr. 2009; 98: 173-179
- The validity and reliability of the diagnosis of hyperkinetic disorders in the Danish Psychiatric Central Research Registry.Eur Psychiatry. 2016; 35: 16-24
- The heritability of clinically diagnosed attention deficit hyperactivity disorder across the lifespan.Psychol Med. 2014; 44: 2223-2229
- Attention-deficit/hyperactivity disorder and risk for substance use disorders in relatives.Biol Psychiatry. 2015; 77: 880-886
- Risk of bipolar disorder and schizophrenia in relatives of people with attention-deficit hyperactivity disorder.Br J Psychiatry. 2013; 203: 103-106
- Serious transport accidents in adults with attention-deficit/hyperactivity disorder and the effect of medication: A population-based study.JAMA Psychiatry. 2014; 71: 319-325
- Attention-deficit/hyperactivity disorder.Nat Rev Dis Primers. 2015; 1: 15020
- Examining the comorbidity between attention deficit hyperactivity disorder and bipolar I disorder: A meta-analysis of family genetic studies.Am J Psychiatry. 2012; 169: 1256-1266
- The co-occurrence of autism and attention deficit hyperactivity disorder in children—What do we know?.Front Hum Neurosci. 2014; 8: 268
- Validation of epilepsy diagnoses in the Danish National Hospital Register.Epilepsy Res. 2007; 75: 162-170
Article info
Publication history
Published online: August 11, 2017
Accepted:
August 8,
2017
Received in revised form:
July 17,
2017
Received:
February 27,
2017
Identification
Copyright
© 2017 Society of Biological Psychiatry.
