Abstracts

Rationale: Depression is the most frequent comorbid psychiatric disorder linked to epilepsy. We examined predictors of depression in affected and unaffected individuals in families containing multiple individuals with epilepsy, with a particular focus on the possible impact of attribution of epilepsy to a genetic cause. Methods: We are surveying previous participants in epilepsy genetics research, to assess the psychosocial impact of having a personal or family history of epilepsy, beliefs about epilepsy genetics, and interest in genetic testing. The survey will target more than 1,000 adult members of 115 families containing multiple individuals with epilepsy (average 4 affected per family). Among 568 participants contacted so far, 490 (86%) have agreed to participate. Here we report results on 324 individuals (135 with epilepsy, 189 unaffected relatives) who completed the survey as of May 1, 2014. We screened for a lifetime history of major depressive disorder (MDD) using a modified version of the Patient Health Questionnaire (PHQ-9) that asks about symptoms in "the 2 weeks in your life that you were the most blue, sad, or depressed." We used three questions to assess participants' attribution of epilepsy to a genetic cause: "In your opinion, how big a role has genetics had in causing the epilepsy in your family?," "What do you think the chances are that you have a change or mutation in a gene that affects risk for epilepsy?," and (in people with epilepsy), "How much do you think genetics or inheritance influenced your risk of developing epilepsy?" Results: A positive screen for a lifetime history of MDD was observed in 34% of individuals with epilepsy and 30% of unaffected relatives. In separate analyses of demographic variables (sex, age, education) in affected and unaffected individuals, the only significant predictor was education (college graduate 42% vs. college graduate 23%, p=.014) among unaffected family members. In individuals with epeilepsy, prevalence of a positive screen for lifetime MDD was greater in those whose last seizure was < 5 vs. ≧ 5 years ago (46% vs. 21%, p=0.005). The proportion who screened positive was also greater in those with > (100 vs. fewer seizures in their lifetime (43% vs. 31%), and in those with generalized vs. focal epilepsy (42% vs. 33%), although these differences were not significant. Participants with epilepsy who believed they had a "moderate" or "high" chance of having an epilepsy-related mutation were more likely to screen positive than others (44% vs. 21%, p=0.007). This association persisted within strata defined by time since last seizure, suggesting it was not due to confounding with this variable. The trend was similar in unaffected individuals (moderate/high chance of having a mutation 37% vs. others 26%, p=0.138). Conclusions: In this study of families with multiple individuals with epilepsy, the strongest predictor of a positive screen for lifetime MDD was having had recent seizures. Individuals who believed they had a moderate or high chance of carrying an epilepsy-related mutation may also have a high lifetime risk of MDD. This research was supported by R01 NS078419.