GABA/Glutamate Balance in Temporal Lobe Epilepsy With and Without Major Depression

Objective: To study the relative balance of GABA (A) binding potential and glutamate utilization in subjects with localization-related epilepsy with and without depression, subjects with major depressive disorder alone, and in subjects with generalized epilepsy (expected not to have significant comorbid depression). Pilot data shows that GABA(A) binding potential and glutamate utilization are tightly coupled in healthy subjects, particularly in the mesial temporal lobe. We hypothesize that subjects with epilepsy will not exhibit the same degree of coupling, and that subjects with both epilepsy and depression will exhibit an even more pronounced decoupling. Study Population: Subjects aged 18-55 with localization-related epilepsy without clinically significant depression, subjects with generalized epilepsy, and healthy controls. Design: This is a neuroimaging study, using positron emission tomography (PET) with \[11C\]flumazenil, to measure GABA(A) binding potential, and \[18F\]fluorodeoxyglucose, to measure glucose utilization (reflective of neuronal glutamate release). Magnetic resonance spectroscopy (MRS) will be used to measure GABA and glutamate in the mesial temporal cortex and corroborate the PET results. Structural magnetic resonance images (MRI) will be obtained for MRS localization and partial volume correction of PET images. Outcome measures: The binding potential of GABA(A), the regional rate of glucose metabolism, and the levels of GABA and glutamate as measured by MRS. Patients will be stratified by seizure type.