Abstracts

Depression and epilepsy are comorbid diseases that seem likely to involve common pathophysiological pathways, including serotonin (5-HT) and 5-HT[sub]1A[/sub] receptors. Two studies have investigated 5-HT[sub]1A[/sub] receptors in patients with temporal lobe epilepsy (TLE) as a function of depressive symptoms and have shown a negative correlation between the binding potential (BP) of [¹¹C]-WAY100635 (WAY) or [18F]-FCWAY and varying depression scales, though in different brain regions. The aim of our work was to study the relationships between 5-HT[sub]1A[/sub] receptor density and the Beck Depression Inventory (BDI) scale in a homogeneous group of patients suffering from TLE with hippocampal sclerosis (HS), using a PET ligand, [¹⁸F]MPPF, which affinity differs from WAY and allows displacement by endogenous serotonin., 21 patients suffering from TLE with HS underwent a [¹⁸F]MPPF-PET. Depressive symptoms were evaluated on the day of the PET study using the BDI scale.
A simplified model was used to generate parametric images of 5-HT[sub]1A[/sub] receptors binding potential values. Images from patients with a left HS were flipped so that HS were on the same side (right) for all patients.
To investigate the association between BP values and BDI scores, we carried out SPM analyses using an ANCOVA design, considering the BDI scores as a covariable of interest, with masks that either included all limbic and paralimbic regions, or the brainstem.
In addition, we placed regions of interest (ROIs) over the same brain regions., SPM analyses disclosed a significant positive association between the MPPF BP values and the BDI scores in the insula contralateral to the seizure focus as well as in the raphe nuclei (p[lt]0.001 and p[lt]0.01 respectively, at the cluster level corrected for multiple comparisons). These results were confirmed by ROI analysis., In contrast with previous WAY-PET studies, we have shown a positive, rather than negative, association between 5-HT[sub]1A[/sub] receptors BP values and the BDI scores, in regions known to be involved in depression (insula, raphe) that also differ from those reported in the previous studies (anterior cingulate, hippocampus). These differences could be partly explained by the lower affinity of MPPF as compared to that of WAY, and reflect decreased level of endogenous 5-HT in the insula and raphe in the more depressed patients., (Supported by Programme Hospitalier de Recherche Clinique.)