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5-HT_1A Receptors Are Reduced in Temporal Lobe Epilepsy After Partial-Volume Correction

¹ PET Department, Clinical Center, National Institutes of Health, Bethesda, Maryland
² Postgraduate Specialty School in Nuclear Medicine, University of Pisa Medical School, Pisa, Italy
³ Clinical Epilepsy Section, National Institute of Neurological Diseases and Strokes, National Institutes of Health, Bethesda, Maryland

Preclinical studies suggest that serotonin 1A receptors (5-HT_1A) play a role in temporal lobe epilepsy (TLE). Previous PET studies reported decreased 5-HT_1A binding ipsilateral to epileptic foci but did not correct for the partial-volume effect (PVE) due to structural atrophy. Methods: We used PET with ¹⁸F-trans-4-fluoro-N-2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl-N-(2-pyridyl)cyclohexanecarboxamide (¹⁸F-FCWAY), a 5-HT_1A receptor antagonist, to study 22 patients with TLE and 10 control subjects. In patients, ¹⁸F-FDG scans also were performed. An automated MR-based partial-volume correction (PVC) algorithm was applied. Psychiatric symptoms were assessed with the Beck Depression Inventory Scale. Results: Before PVC, significant (uncorrected P < 0.05) reductions of ¹⁸F-FCWAY binding potential (BP) were detected in both mesial and lateral temporal structures, mainly ipsilateral to the seizure focus, in the insula, and in the raphe. Group differences were maximal in ipsilateral mesial temporal regions (corrected P < 0.05). After PVC, differences in mesial, but not lateral, temporal structures and in the insula remained highly significant (corrected P < 0.05). Significant (uncorrected P < 0.05) BP reductions were also detected in TLE patients with normal MR images (n = 6), in mesial temporal structures. After PVC, asymmetries in BP remained significantly greater than for glucose metabolism in hippocampus and parahippocampus. There was a significant inverse relation between the Beck Depression score and the ipsilateral hippocampal BP, both before and after PVC. Conclusion: Our study shows that in TLE patients, reductions of 5-HT_1A receptor binding in mesial temporal structures and insula are still significant after PVC. In contrast, partial-volume effects may be an important contributor to 5-HT_1A receptor-binding reductions in lateral temporal lobe. Reduction of 5-HT_1A receptors in the ipsilateral hippocampus may contribute to depressive symptoms in TLE patients.

Key Words: 5-HT_1A receptors • temporal lobe epilepsy • partial-volume correction • PET • depression

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