Familial Liability to Epilepsy and Attention-Deficit/Hyperactivity Disorder: A Nationwide Cohort Study

Brikell, Isabell; Ghirardi, Laura; D’Onofrio, Brian M.; Dunn, David W.; Almqvist, Catarina; Dalsgaard, Søren; Kuja‐Halkola, Ralf; Larsson, Henrik

doi:10.1016/j.biopsych.2017.08.006

Cited by 64 publications

(45 citation statements)

References 53 publications

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“…Prevalence of ADHD in children with epilepsy is reported as 30%‐40% in targeted studies and 12.5%‐15% in a nontargeted, population registry study, overall a rate 2.5 to 5.5 times higher than in otherwise healthy children without seizures. Attention problems often predate onset of seizures . The predominantly inattentive type of ADHD is more prevalent in patients with epilepsy .…”

Section: Introductionmentioning

confidence: 99%

“…Attention problems often predate onset of seizures. 6,7 The predominantly inattentive type of ADHD is more prevalent in patients with epilepsy. 5,9,10 A large, population-based cohort study has suggested that both genetic and environmental factors contribute to this comorbidity.…”

Section: Introductionmentioning

confidence: 99%

“…5,9,10 A large, population-based cohort study has suggested that both genetic and environmental factors contribute to this comorbidity. 7 The impact of comorbid ADHD in people with epilepsy is significant, often associated with academic and vocational underachievement, depression, and anxiety. 8,9 Key points • Risk factors for ADHD in children with epilepsy include comorbid developmental disabilities, as well as poor seizure control • Data support the ability of the Strengths and Difficulties Questionnaire to predict ADHD diagnosis in children with epilepsy • Polytherapy is more associated with behavioral problems than monotherapy • Valproate can exacerbate attentional issues in children with Childhood Absence Epilepsy • Methylphenidate is tolerated and effective in children with epilepsy and comorbid ADHD Furthermore, ADHD is underdiagnosed in children with epilepsy, 10 as difficulties with attention and behavior are attributed to the epilepsy itself, or to the effects of antiepileptic drugs (AEDs).…”

Section: Introductionmentioning

confidence: 99%

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Systematic review of the screening, diagnosis, and management of ADHD in children with epilepsy. Consensus paper of the Task Force on Comorbidities of the ILAE Pediatric Commission

et al. 2018

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Attention-deficit/hyperactivity disorder (ADHD) is a common and challenging comorbidity affecting many children with epilepsy. A working group under the International League Against Epilepsy (ILAE) Pediatric Commission identified key questions on the identification and management of ADHD in children with epilepsy. Systematic reviews of the evidence to support approaches to these questions were collated and graded using criteria from the American Academy of Neurology Practice Parameter. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) requirements were followed, with PROSPERO registration (CRD42018094617). No increased risk of ADHD in boys with epilepsy compared to girls with epilepsy was found (Level A). Valproate use in pregnancy is associated with inattentiveness and hyperactivity in offspring (1 class I study), and children with intellectual and developmental disabilities are at increased risk of ADHD (Level A). Impact of early seizure onset on development of ADHD was unclear (Level U), but more evident with poor seizure control (Level B). ADHD screening should be performed from 6 years of age, or at diagnosis, and repeated annually (Level U) and reevaluated after change of antiepileptic drug (AED) (Level U). Diagnosis should involve health practitioners with expert training in ADHD (Level U). Use of the Strength and Difficulties Questionnaire screening tool is supported (Level B). Formal cognitive testing is strongly recommended in children with epilepsy who are struggling at school (Level U). Behavioral problems are more likely with polytherapy than monotherapy (Level C). Valproate can exacerbate attentional issues in children with childhood absence epilepsy (Level A). Methylphenidate is tolerated and effective in children with epilepsy (Level B). Limited evidence supports that atomoxetine is tolerated (Level C). Multidisciplinary involvement in transition and adult ADHD clinics is essential (Level U). In conclusion, although recommendations could be proposed for some of the study questions, this systematic review highlighted the need for more comprehensive and targeted large-population prospective studies.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Systematic review of the screening, diagnosis, and management of ADHD in children with epilepsy. Consensus paper of the Task Force on Comorbidities of the ILAE Pediatric Commission

et al. 2018

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“…Only a few twin and family studies have explored how genetic factors contribute to non-psychiatric comorbidity. The literature suggests novel etiologic links with asthma [64], obesity [65], and epilepsy [66].…”

Section: Psychiatric Comorbiditymentioning

confidence: 99%

Genetics of attention deficit hyperactivity disorder

2018

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Decades of research show that genes play an vital role in the etiology of attention deficit hyperactivity disorder (ADHD) and its comorbidity with other disorders. Family, twin, and adoption studies show that ADHD runs in families. ADHD's high heritability of 74% motivated the search for ADHD susceptibility genes. Genetic linkage studies show that the effects of DNA risk variants on ADHD must, individually, be very small. Genome-wide association studies (GWAS) have implicated several genetic loci at the genome-wide level of statistical significance. These studies also show that about a third of ADHD's heritability is due to a polygenic component comprising many common variants each having small effects. From studies of copy number variants we have also learned that the rare insertions or deletions account for part of ADHD's heritability. These findings have implicated new biological pathways that may eventually have implications for treatment development.Attention deficit hyperactivity disorder (ADHD) is a childhood-onset condition with impairing symptoms of inattention, impulsivity, and hyperactivity. Decades of research have documented and replicated key facts about the disorder (for a review, see ref.[1]). It occurs in about 5% of children with little geographic or cross-cultural variation in prevalence and often co-occurs with other conditions, including mood, anxiety, conduct, learning, and substance use disorders. Longitudinal studies show that two-thirds of ADHD youth will continue to have impairing symptoms of ADHD in adulthood. People with ADHD are at risk for a wide range of functional impairments: school failure, peer rejection, injuries due to accidents, criminal behavior, occupational failure, divorce, suicide, and premature death. Although many details of ADHD's pathophysiology are unknown, neuropsychological and neuroimaging studies implicate brain circuits regulating executive functioning, reward processing, timing, and temporal information processing.This article reviews data about the role that genes play in the etiology of ADHD from two perspectives. Family, twin, and adoption studies provide a firm foundation for asserting that genes are involved in the etiology of ADHD. The view from molecular genetics provides a basis for understanding mechanisms whereby genes affect biological pathways that lead to ADHD. Family, twin and adoption studies of ADHDEvidence for heritability from family, adoption, and twin studies A study of 894 ADHD probands and 1135 of their siblings aged 5-17 years old found a ninefold increased risk of ADHD in siblings of ADHD probands compared with siblings of controls [2]. Adoption studies suggest that the familial factors of ADHD are attributable to genetic factors rather than shared environmental factors [3,4] with the most recent one reporting rates of ADHD to be greater among biological relatives of non-adopted ADHD children than adoptive relatives of adopted ADHD children. The adoptive relatives had a risk for ADHD like the risk in relatives of control childr...

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“…Patients with epilepsy have a three‐ to five‐fold increased risk of attention‐deficit/hyperactivity disorder (ADHD) diagnosis, and 20%‐50% of children with epilepsy exhibit subclinical ADHD symptoms . Untreated, ADHD is associated with severe adverse outcomes, making effective treatment crucial.…”

Section: Introductionmentioning

confidence: 99%

Medication treatment for attention‐deficit/hyperactivity disorder and the risk of acute seizures in individuals with epilepsy

et al. 2019

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Summary Objective Attention‐deficit/hyperactivity disorder (ADHD) affects 10%‐30% of individuals with epilepsy, yet concerns remain regarding the safety of ADHD medication in this group. The objective of this study was to examine the risk of acute seizures associated with ADHD medication in individuals with epilepsy. Methods A total of 21 557 individuals with a seizure history born between 1987 and 2003 were identified from Swedish population registers. Within this study population, we also identified 6773 youth (<19 years of age) who meet criteria for epilepsy, and 1605 youth with continuous antiepileptic drug (AED) treatment. ADHD medication initiation and repeated medication periods were identified from the Swedish Prescribed Drug Register between January 1, 2006 and December 31, 2013. Acute seizures were identified via unplanned visits to hospital or specialist care with a primary seizure discharge diagnosis in the Swedish National Patient Register during the same period. Conditional Poisson regression was used to compare the seizure rate during the 24 weeks before and after initiation of ADHD medication with the rate during the same 48 weeks in the previous year. Cox regression was used to compare the seizure rate during ADHD medication periods with the rate during nonmedication periods. Comparisons were made within‐individual to adjust for unmeasured, time?constant confounding. Results Among 995 individuals who initiated ADHD medication during follow‐up, within‐individual analyses showed no statistically significant difference in the rate of seizures during the 24 weeks before and after medication initiation, compared to the same period in the previous year. In the full study population 11 754 seizure events occurred during 136 846 person‐years and 1855 individuals had at least one ADHD medication period. ADHD medication periods were associated with a reduced rate of acute seizures (hazard ratio [HR] 0.73, 95% confidence interval [CI] 0.57‐0.94), compared to nonmedication periods within the same individual. Similar associations were found in youth with epilepsy and continuous AED treatment, when adjusting for AEDs, and across sex, age, and comorbid neurodevelopmental disorders. Significance We found no evidence for an overall increased rate of acute seizures associated with ADHD medication treatment among individuals with epilepsy. These results suggest that epilepsy should not automatically preclude patients from receiving ADHD medications.

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Familial Liability to Epilepsy and Attention-Deficit/Hyperactivity Disorder: A Nationwide Cohort Study

Cited by 64 publications

References 53 publications

Systematic review of the screening, diagnosis, and management of ADHD in children with epilepsy. Consensus paper of the Task Force on Comorbidities of the ILAE Pediatric Commission

Systematic review of the screening, diagnosis, and management of ADHD in children with epilepsy. Consensus paper of the Task Force on Comorbidities of the ILAE Pediatric Commission

Genetics of attention deficit hyperactivity disorder

Medication treatment for attention‐deficit/hyperactivity disorder and the risk of acute seizures in individuals with epilepsy

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