5-HT 1A receptors are reduced in temporal lobe epilepsy after partial-volume correction

Abstract

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.

FIGURE 1.

Coronal T2-weighted (A, top) and T1-weighed (A, bottom) MR images of patient with TLE with a right mesial temporal focus and coregistered ¹⁸F-FCWAY distribution volume (V/f 1, B) and CMRglu (C) images before (top) and after (bottom) PVC. Coronal images are at level of posterior hippocampus, anterior to pons. V/f 1 and CMRglu images are scaled to a maximum of 100 mL/mL and 10 mg/min/100 g, respectively.

FIGURE 2.

Relationship between percentage increase in ¹⁸FFCWAY distribution volume (V/f₁, mL/mL) and CMRglu (mg/min/ 100 g) in TLE patients. Each point represents mean ROI value. Regression equation was V = 21.5 + 0.90 CMRglu; r² = 0.95; P < 0.001. Dashed line represents identity line.

FIGURE 3.

Relationship between ¹⁸F-FCWAY BP (mL/mL) in hippocampus ipsilateral to seizure focus and BDI scale score in TLE patients before (A) and after (B) PVC. Regression equations were y = 47.6 - 1.24x ; r² = 0.35, P = 0.004 (A) and y = 81.2 - 1.97x ; r² = 0.26, P = 0.016 (B).