Abstracts

Rationale: Previous positron emission tomography (PET) studies found reduced serotonin (5HT1A) receptor binding in depression and temporal lobe epilepsy (TLE), suggesting altered serotonergic neurotransmission. Some studies showed altered 5HT transport (5HTT) in patients with depression. We investigated 5HTT and 5HT1A binding in epilepsy.Methods: Eleven healthy controls, 7 patients with frontal-onset epilepsy (FLE), and 13 patients with unilateral TLE (9 left-sided) on ictal video-electroencephalography monitoring had PET with 11C-DASB, a highly selective 5HTT tracer, and 18F-FCWAY, a highly selective 5HT1A receptor radioligand. Subjects had 3T T1 MPRAGE or 1.5T SPGR MRI to co-register PET images using statistical parametric mapping (SPM2). PET and structural MRI images were normalized to a standard T1 MNI template. Gray matter (GM) masks were generated in SPM2 for each subject, and GM segments applied to corresponding normalized PET images using MEDx. FCWAY images had MRI-based partial volume correction for structural atrophy. Regions of interest (ROIs) drawn on a normalized control MRI were applied to DASB and FCWAY images. For DASB, a mean voxel by voxel binding parameter (BP) was generated for each left and right-sided ROI. For FCWAY, free-fraction corrected 5HT1A receptor volume of distribution was extracted for each ROI. For both FCWAY and DASB, asymmetry indexes (AIs) were computed using the formula AI=200*(R-L)/(R+L). The side of patients seizure foci was standardized so that a positive AI signified reduced ipsilateral binding. Results: DASB mean AIs did not differ significantly between healthy controls, frontal lobe epilepsy patients, and TLE patients. The mean FCWAY amygdala AI was significantly higher in TLE patients compared to controls and FLE (p<0.05). TLE patients with a history of depression had a significantly higher parahippocampal gyrus DASB AI (p<0.05). There was a significant inverse correlation between epilepsy duration and DASB mean hippocampal AI for frontal and TLE patients (p<0.05). There was a significant correlation between DASB and FCWAY mean AI in insula, inferior temporal lobe, and cingulate cortex in TLE patients (p<0.05).Conclusions: Decreased ipsilateral amygdala 5HT1A binding in TLE supports previous findings of reduced binding in mesial and neighboring temporal structures. Increased hippocampal 5HTT in patients with longer epilepsy duration complements previous findings of increased 5HTT mRNA in TLE patients and could suggest a progressively pro-convulsant environment due to greater 5HT reuptake. The positive correlation between 5HT1A and 5HTT binding in several regions in TLE patients suggests compensatory changes contrasting with an inverse correlation found in similar regions in healthy male controls from other studies.