Abstracts

Rationale: Depression is the most common comorbid psychiatric condition in individuals with epilepsy, but the cause of this comorbidity is unknown. One possible explanation is a shared genetic susceptibility to the two disorders. Although some evidence supports this possibility, previous studies have not clearly distinguished between shared genetic susceptibility and reactions to having a chronic stigmatizing disorder. We addressed this problem by investigating depression in families with a known genetic cause of epilepsy, i.e., families with autosomal dominant partial epilepsy with auditory features (ADPEAF) with mutations in the leucine-rich, glioma inactivated 1 gene (LGI1). Methods: We administered a standardized depression interview (PHQ-9) to 70 members of 8 families, each of which had a different mutation in LGI1. The PHQ-9 is a widely used 9-item depression screen and diagnostic tool designed to detect current (i.e., previous 2 weeks) major depressive disorder and other depressive disorder as well as to assess current depression symptoms using a quantitative symptom severity scale. We classified family members into three groups: mutation carriers with epilepsy (n=25), mutation carriers without epilepsy (n=9), and non-carriers (n=36). We attempted to disentangle the effects of LGI1 mutations from those of epilepsy and its treatment by examining depression risks separately in mutation carriers with and without epilepsy, compared with non-carriers. Analyses adjusted for the non-independence of individuals within the same family. Results: Only two subjects, both of whom were mutation carriers with epilepsy (8%), met criteria for current major depressive disorder. Nine subjects met criteria for current other depressive disorder. The risk for current other depressive disorder was increased non-significantly in both mutation carriers with epilepsy (OR=2.10, 95% CI=0.42 - 10.51) and mutation carriers without epilepsy (OR=3.14, 95% CI=0.37 - 26.37), compared with non-carriers. Current depression symptom scores were significantly higher in mutation carriers with epilepsy than non-carriers (mean = 5.4 vs. 1.9, p=0.003). However, current depression symptom scores were not higher in mutation carriers without epilepsy than non-carriers (mean = 2.3 vs. 1.9, p=0.71). Conclusions: In this small study, current other depressive disorder (i.e., previous 2 weeks) was elevated in LGI1 mutation carriers both with and without epilepsy whereas current depressive symptoms were only increased in LGI1 mutation carriers with epilepsy. While the results for other depressive disorder are suggestive of a shared genetic susceptibility, analyses of current depressive symptoms suggest that the comorbidity of depression and epilepsy is related to having epilepsy. This could be due to a reaction to the stigma associated with the disorder, the depressogenic effects of the treatments for epilepsy, or the effects of seizures on the brain. Future studies, using a larger sample and assessing lifetime rather than current depression, could help to clarify whether or not depression is an alternative manifestation of LGI1 mutations.