Limbic reductions of 5-HT 1A receptor binding in human temporal lobe epilepsy

Abstract

Objective: To test the hypothesis that in mesial temporal lobe epilepsy (MTLE) there is involvement outside of mesial structures and that this involvement affects serotonin systems, thus suggesting a mechanism for affective symptoms in this population. Methods: Serotonin 5-HT_1A receptor binding was studied with PET and [Carbonyl-¹¹C]WAY-100 635 in 14 patients (6 with left-, 8 with right-sided mesial temporal lobe focus) and 14 controls. The 5-HT_1A receptor binding potential was calculated for hippocampus, amygdala, orbitofrontal, insular, lateral temporal, and anterior cingulate cortex, in raphe nuclei, and in two regions presumably uninvolved in the epileptogenic process (parietal, and dorsolateral frontal neocortex). Results: The binding potential was reduced in the epileptogenic hippocampus (p = 0.0001) and amygdala (p = 0.0001) in all patients, including the six with normal [¹⁸F]FDG PET and MRI. It was also reduced in the anterior cingulate (p = 0.002), insular (p = 0.015), and lateral temporal cortex (p = 0.029) ipsilaterally to the focus, in contralateral hippocampus (p = 0.025), and in the raphe nuclei (p = 0.016). Conclusion: Patients with severe MTLE show reduced 5-HT_1A receptor binding potential in the EEG-focus, and its limbic connections. [¹¹C]WAY-100 635 PET may provide additional information to EEG, [¹⁸F]FDG PET, and MRI when evaluating patients with intractable seizures. Reductions in 5-HT_1A binding in the insula and cingulate suggest a mechanism by which affective symptoms in MTLE may result.