Depression and genetic causal attribution of epilepsy in multiplex epilepsy families

Abstract

Summary Objectives Rapid advances in genetic research and increased use of genetic testing have increased the emphasis on genetic causes of epilepsy in patient encounters. Research in other disorders suggests that genetic causal attributions can influence patients’ psychological responses and coping strategies, but little is currently known about how epilepsy patients and their relatives will respond to genetic attributions of epilepsy. We investigated the possibility that depression, the most frequent psychiatric comorbidity in the epilepsies, might be related to the perception that epilepsy has a genetic cause among members of families containing multiple individuals with epilepsy. Methods A self-administered survey was completed by 417 individuals in 104 families averaging four individuals with epilepsy per family. Current depression was measured with the PHQ-9. Genetic causal attribution was assessed by three questions addressing: perceived likelihood of having an epilepsy-related mutation, perceived role of genetics in causing epilepsy in the family, and (in individuals with epilepsy) perceived influence of genetics in causing the individual’s epilepsy. Relatives without epilepsy were asked about their perceived chance of developing epilepsy in the future, compared with the average person. Results Prevalence of current depression was 14.8% in 182 individuals with epilepsy, 6.5% in 184 biological relatives without epilepsy, and 3.9% in 51 married-in individuals. Among individuals with epilepsy, depression was unrelated to genetic attribution. Among biological relatives without epilepsy, however, prevalence of depression increased with increasing perceived chance of having an epilepsy-related mutation (p=0.02). This association was not mediated by perceived future epilepsy risk among relatives without epilepsy. Significance Depression is associated with perceived likelihood of carrying an epilepsy-related mutation among individuals without epilepsy in families containing multiple affected individuals. This association should be considered when addressing mental health issues in such families.

Genetic attribution and perceived impact of epilepsy in multiplex epilepsy families

“…Notably, being unemployed was associated in bivariate analyses with having a higher IES score (PR = 1.4, 95% confidence interval [CI] = 1.06-1.84). We previously showed that these seizure variables were also associated with genetic attribution, 19 leading to their inclusion in our adjusted models as potential confounders. Increasing number of lifetime seizures and time since last seizure ≤ 5 years were both significantly associated with high IES score ( Table 2).…”

“…19 Similarly, one might expect that having many relatives with epilepsy could influence perceived impact of epilepsy in both affected and unaffected people through items such as "Your relationship with other close members of your family" and possibly "Your relationship with your spouse/partner," but contrary to this expectation, number of affected relatives was not associated with the IES (Table 2). 19 Similarly, one might expect that having many relatives with epilepsy could influence perceived impact of epilepsy in both affected and unaffected people through items such as "Your relationship with other close members of your family" and possibly "Your relationship with your spouse/partner," but contrary to this expectation, number of affected relatives was not associated with the IES (Table 2).…”

“…19 The first asked, "In your opinion, how big a role has genetics had in causing the epilepsy in your family?" 19 The first asked, "In your opinion, how big a role has genetics had in causing the epilepsy in your family?"…”

“…To date, results indicate that interest in genetic testing for oneself or one's offspring is strong, especially if genetic findings are likely to have clinical utility. 19 Based on previous findings, we hypothesized that the psychosocial impact of epilepsy would be higher among people who attributed their epilepsy to a genetic cause than among others. 18 Additionally, among family members without epilepsy, the perceived chance of having an epilepsy-related mutation was associated with increased prevalence of depressive symptoms.…”

“…18 Additionally, among family members without epilepsy, the perceived chance of having an epilepsy-related mutation was associated with increased prevalence of depressive symptoms. 19 Based on previous findings, we hypothesized that the psychosocial impact of epilepsy would be higher among people who attributed their epilepsy to a genetic cause than among others. To test this hypothesis, we examined the relations of responses on the Impact of Epilepsy Scale (IES), 12 a previously validated measure of the impact of epilepsy, with measures of genetic causal attribution of epilepsy.…”