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Mood disorders are the most common comorbid conditions in epilepsy, but the cause remains unclear. One possible explanation is a shared genetic susceptibility to epilepsy and mood disorders. We tested this hypothesis by evaluating lifetime prevalence of mood disorders in relatives with and without epilepsy in families containing multiple individuals with epilepsy, and comparing the findings with rates from a general population sample.

The Composite International Diagnostic Interview was administered to 192 individuals from 60 families, including 110 participants with epilepsy of unknown cause (50 focal epilepsy [FE], 42 generalized epilepsy [GE], 6 FE and GE, 12 unclassifiable) and 82 relatives without epilepsy (RWOE). Odds ratios (ORs) for lifetime prevalence of mood disorders in participants with versus without epilepsy were computed through logistic regression, using generalized estimation equations to account for familial clustering. Standardized prevalence ratios (SPRs) were used to compare prevalence in family members with general population rates.

Compared with RWOE, ORs for mood disorders were significantly increased in participants with FE (OR = 2.4, 95% confidence interval [CI] = 1.1-5.2) but not in those with GE (OR = 1.0, 95% CI = 0.4-2.2). In addition, prevalence of mood disorders was increased in individuals with epilepsy who had ≥1 relative with FE. Compared with general population rates, mood disorders were significantly increased in individuals with FE but not in those with GE. Rates were also increased in RWOE, but not significantly so (SPR = 1.4, P = .14).

These findings are consistent with the hypothesis of shared genetic susceptibility to epilepsy and mood disorders, but suggest (1) the effect may be restricted to FE, and (2) the shared genetic effect on risk of mood disorders and epilepsy may be restricted to individuals with epilepsy, that is, to those in whom the genetic risk for epilepsy is “penetrant.”