Limbic reductions of 5-HT1A receptor binding in human temporal lobe epilepsy.
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-HT1A 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-HT1A 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).


CONCLUSIONS
Patients with severe MTLE show reduced 5-HT1A receptor binding potential in the EEG-focus, and its limbic connections. [(11)C]WAY-100 635 PET may provide additional information to EEG, [18F]FDG PET, and MRI when evaluating patients with intractable seizures. Reductions in 5-HT1A binding in the insula and cingulate suggest a mechanism by which affective symptoms in MTLE may result.
Savic
I
I
Division of Human Brain Research, Department of Neuroscience, Karolinska Institute, Stockholm, Sweden. ivanka.savic-berglund@neuro.ki.se
Lindström
P
P
Gulyás
B
B
Halldin
C
C
Andrée
B
B
Farde
L
L
D000328:Adult; D000679:Amygdala / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D001007:Anxiety / Q000175:diagnosis; D001667:Binding, Competitive; D015415:Biomarkers / Q000032:analysis; D002250:Carbon Radioisotopes; D002531:Cerebellum / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D003863:Depression / Q000175:diagnosis; D004569:Electroencephalography; D004833:Epilepsy, Temporal Lobe / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000503:physiopathology*; D005260:Female; D005462:Fluorine Radioisotopes; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D006179:Gyrus Cinguli / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D006624:Hippocampus / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008024:Ligands; D008032:Limbic System / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000493:pharmacokinetics; D011237:Predictive Value of Tests; D011725:Pyridines / Q000493:pharmacokinetics; D011903:Raphe Nuclei / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D012016:Reference Values; D012702:Serotonin Antagonists / Q000493:pharmacokinetics; D014055:Tomography, Emission-Computed
D015415:Biomarkers; D002250:Carbon Radioisotopes; D005462:Fluorine Radioisotopes; D008024:Ligands; D010879:Piperazines; D011725:Pyridines; D012702:Serotonin Antagonists; D019788:Fluorodeoxyglucose F18; D044282:Receptor, Serotonin, 5-HT1A; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide