Psychopathology and seizure threshold.

Commentary This expertly designed, conducted, and analyzed study adds to prior studies that have examined the bidirectional association between psychopathology and epilepsy. Adelöw et al. (1) recently provided robust prospective data in a population-based case-control study using the Stockholm Epilepsy Register that confirmed this relationship in individuals hospitalized for a wide range of psychiatric disorders following an unprovoked seizure. In the Hesdorffer et al. prospective UK General Practice Research Database (GRPD), findings in individuals who were not selected because of psychiatric hospitalization suggest that the bidirectional association is not merely a function of the severity of psychiatric illness. Similar to Adelöw et al., the prevalence and incidence of a wide range of psychiatric diagnoses and suicidality underscore that the association between psychopathology and epilepsy is not a function of the type of psychiatric disorder. Further, it does not appear to be a function of epilepsy syndrome, as most of the subjects in both studies had idiopathic and cryptogenic epilepsy. However, since those in Adelöw et al. had predominantly focal seizures and this information is lacking in Hesdorffer et al., it remains to be determined if type of seizures (i.e., focal seizures) is related to the more severe psychopathology that necessitates psychiatric hospitalization. Based on the study's prospective findings of incident epilepsy subsequent to psychiatric diagnoses, Hesdorffer and colleagues concluded that psychopathology lowers the seizure threshold rather than increases the propensity for seizures. Animal studies have shown that Genetic Absence Epilepsy Rats from Strasbourg (GAERS) with absence-like seizures demonstrate behaviors thought to represent anxiety before and subsequent to the onset of seizures (2). Jones et al. (2) concluded that these findings suggest that anxiety and absence seizures share common mechanisms. However, the pilocarpine animal model of temporal lobe epilepsy (TLE) manifests behavior equivalents of depression and involves lesions of the hippocampus and amygdala, as well as an increase in corticosterone and activity of the HPA axis (3). In contrast, the kainate model of TLE does not demonstrate depression, has minimal involvement of the amygdala and hippocampus, and is unrelated to an increase in corticoste-rone (3). Thus, different mechanisms appear to underlie the relationship between type of psychopathology (anxiety and depression) and type of seizures (absence and focal seizures) in animal models of epilepsy. Therefore, in the absence of specific measures of seizure threshold in Hesdorffer et al., markedly different variables across individuals might contribute to the study's findings of an increased …