Abstracts

Rationale: Temporal lobe epilepsy (TLE) is the most frequent epilepsy in adults. In addition to seizures, patients with TLE have a high prevalence of depression, estimated at up to 35% (vs 5-7% in the general population) and higher than in patients with other chronic diseases. TLE-associated depression is thus a major factor in reducing quality of life, and may result in suicide in up to an 11%. Despite the clear importance of TLE-associated depression, its origins are not well understood. Whereas depression is often thought to result from the TLE, we tested the alternative hypothesis, that the insult that causes TLE might also provoke depression. We used an animal model of Febrile Status Epilepticus (FSE), a strong risk factor for TLE in humans and a direct cause of TLE in rodents. Specifically we examined if FSE in immature rats leads to depression-like behaviors. Methods: Experimental FSE was induced in rats on post-natal day 10 (n=11). Rats that experienced FSE and normothermic controls (n=6) were implanted with cortical and bipolar electrodes one month after FSE and monitored for the presence of limbic seizures and interictal activity for 12 months. Experimental and control rats were tested for depression-like behaviors at 3 and 12 months of age, using the forced swim test. Results: Three months after FSE, the duration of immobility, a measure of depression-like behavior, was quite similar and tightly clustered in the normal range in the normothermic control group. In contrast, duration of immobility was significantly increased in a subset of rats that experienced FSE. When compared to the mean ± two standard deviations of the normothermic control rats, values were above this range in 4/11 FSE rats. Two out of these four rats developed spontaneous recurrent seizures (TLE) starting after the occurrence of depression-like behaviors. The depression-like behaviors at 10 months of age are under analysis. Conclusions: These initial data suggest: (a) an insult known to cause TLE may provoke depression-like behaviors that precede TLE onset; (b) there is only a partial overlap between TLE and depression after an early-life insult that affects the limbic circuit. Still, the data suggest that in TLE, depression and epilepsy may evolve from the same insult, rather than TLE being the direct cause of depression. Supported by NIH grants NS35439, NS78279 and the Hewitt foundation.