CHICAGO—ADHD, depression, and suicidality are associated with an increased risk for pediatric epilepsy, reported Dale Hesdorffer, PhD, at the 55th Annual Meeting of the American Academy of Child and Adolescent Psychiatry. Dr. Hesdorffer reviewed the evidence linking these neuropsychiatric comorbidities, as well as migraine, as risk factors for seizures.

ADHD, Depression, and Suicidality
Many cross-sectional studies have revealed an increase in comorbidity of ADHD and epilepsy, said Dr. Hesdorffer, Associate Professor of Clinical Epidemiology at the Mailman School of Public Health at Columbia University in New York City. In a case-control study of 109 Icelandic children ages 3 to 16 with newly diagnosed unprovoked seizure and 218 age- and gender-matched controls, Dr. Hesdorffer and her colleagues found that ADHD was associated with an increased risk for seizures. This association was greater for the inattentive type of ADHD (odds ratio [OR], 3.7) than for the hyperactive-impulsive type (OR, 1.8) or the combined type (OR, 2.5). In addition, onset of ADHD occurred at a younger age in those with seizures than in controls, especially for those with the inattentive type of ADHD.

In another study conducted by Jones et al, 26.4% of 53 children ages 8 to 18 who had idiopathic epilepsy for less than one year and 10% of 50 healthy children had ADHD. The investigators found an increase in frontal lobe volume measured by quantitative MRI in children with both new-onset epilepsy and ADHD, compared with children with ADHD who did not have epilepsy or control subjects with neither condition. “Higher frontal lobe volume suggests the possibility of a shared substrate that may explain both ADHD and epilepsy and may account developmentally for the earlier age of onset of seizures observed in the Icelandic population,” Dr. Hesdorffer noted.

Depression also occurs more often in patients with epilepsy than in healthy controls or those with other medical illnesses, such as cardiac conditions or diabetes, reported Dr. Hesdorffer. In a case-control study of the Icelandic population, patients with idiopathic epilepsy (n = 324) had a 1.9-fold increased risk for major depression, compared with age- and gender-matched controls (n = 647). According to Dr. Hesdorffer, the reasons for this shared susceptibility to depression and epilepsy are still unknown but may be related to serotoninergic systems.

Findings from the Icelandic case-control study also showed that attempted suicide was associated with a 3.5-fold increased risk for seizures, even after adjusting for major depression, socioeconomic status, age, gender, and alcohol use. This may explain why people with epilepsy have a greatly increased risk for completed suicide, as suicidality tends to recur.

A Link Between Migraine and Epilepsy?
The combination of migraine with aura and major depressive disorder was associated with a 4.5 times greater risk for seizures, which was greater than the risk for seizures with migraine with aura alone (two times) or major depressive disorder alone (1.5 times), said Dr. Hesdorffer. Similar results were seen with the combination of migraine and suicidality, which was associated with an eight times greater risk for seizures, compared with two times for migraine with aura alone or 4.5 times for suicidality alone.

Identification of Neuropsychiatric Comorbidities Is Crucial
Psychopathology is often underrecognized and undertreated in children and adolescents with epilepsy, reported Sigita Plioplys, MD, in a separate presentation. Despite the fact that approximately 60% of patients with epilepsy have a psychiatric diagnosis, less than 40% receive psychiatric services, noted Dr. Plioplys, Associate Professor in the Department of Psychiatry and Behavioral Sciences, Feinberg School of Medicine, Northwestern University in Chicago. “Limited resources in mental health services, lack of awareness among neurologists and parents, and the ‘double stigma’ of having epilepsy and mental health problems contribute to this high rate of undertreatment,” she commented.

Dr. Plioplys pointed out that it is important to identify children with epilepsy who are at risk for psychopathology early in the course of their illness to initiate treatment and improve outcomes. “All children with epilepsy should receive a comprehensive psychiatric diagnostic evaluation that includes a thorough assessment of epilepsy-related cognitive, linguistic, and family variables,” she said.

Avenues for Further Research
“Future research is needed to evaluate prognosis, characterize phenotypes, explore the role of common underlying risk factors, and elucidate shared pathogenesis and genetic susceptibility of epilepsy and comorbid neuropsychiatric conditions,” Dr. Hesdorffer suggested.

Also, additional research “needs to include genetic testing to identify the primary underlying CNS disorder that presents with seizures and behavioral problems and to guide selection of optimal pharmacologic treatment. In addition, structural and functional brain imaging may help identify children with epilepsy at risk for memory, information processing, language, emotional, and social deficits, as well as monitor the beneficial and detrimental effects of antiepileptic medications,” concluded Dr. Plioplys.

—Andrew N. Wilner, MD

Neuropsychiatric Comorbidities Increase the Risk for Epilepsy in Children