Abstracts

Rationale: Up to 50% of patients with temporal lobe epilepsy (TLE) suffer from depression. However, it is unclear which patient will develop depression. Early predictive biomarkers are required for potential intervention. Thirty-70% of individuals with TLE have a history of febrile status epilepticus (FSE), which thus might be an important contributor to this epilepsy. In an animal model where TLE directly results from FSE, we found a subset of rats that manifested depressive-like behaviors. Here we tested if depressive-like behaviors in the context of FSE-related TLE can be predicted early, as well as examined their neurobiological mechanisms.Methods: FSE-experiencing rats (n=11), normothermic controls (n=6) underwent MR imaging (using an 11.7T Bruker MRI system) ~18 hours following FSE. T₂ relaxation time maps were generated and T₂ values were measured in dorsal and ventral hippocampus and amygdala, regions implicated in both limbic epilepsy and depression, as well as in other brain regions. Rats were implanted with hippocampal electrodes one month after FSE and monitored for the presence of limbic seizures for 10 months, and power spectral analyses of the EEG were generated. Animals were tested for depression-like behaviors at 3 months of age, using the forced swim test. Results: Four of 11 FSE rats demonstrated depressive-like behavior in the forced swim test (duration of immobility higher than two standard deviations compared with controls). Testing if MRI T₂ values predicted the development of depressive-like behaviors, we found that 18 h post FSE, T₂ values in ventral hippocampal CA1 of FSE rats that developed depressive-like behaviors were significantly lower than those in controls and in non-depressed FSE rats. EEG spectral analyses distinguished the depressed rats from both normothermic controls and non depressed FSE rats: A peak in theta range (4-12Hz) had a significanlty higher amplitude in depressed FSE rats compared to the two other groups.Conclusions: (a) Decreased MRI T₂ values in ventral hippocampus ~18 hours after FSE predict the development of depressive-like behaviors. (b) Depressive-like behaviors in FSE rats are linked to augmented theta activity in ventral hippocampus. Although the underlying mechanisms for depressive-like behaviors in TLE remain to be elucidated, the current findings may provide novel predictive markers for depression in patients with TLE, with a major impact on potential intervention. Supported by R37 NS35439 (TZB).