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High brain serotonin levels in migraine between attacks: A 5-HT4 receptor binding PET study.

High brain serotonin levels in migraine between attacks: A 5-HT4 receptor binding PET study.
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Deen M, Hansen HD, Hougaard A, Nørgaard M, Eiberg H, Lehel S, Ashina M, Knudsen GM,


Deen M, Hansen HD, Hougaard A, Nørgaard M, Eiberg H, Lehel S, Ashina M, Knudsen GM, (click to view)

Deen M, Hansen HD, Hougaard A, Nørgaard M, Eiberg H, Lehel S, Ashina M, Knudsen GM,

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NeuroImage. Clinical 2018 01 2818() 97-102 doi 10.1016/j.nicl.2018.01.016
Abstract

Migraine has been hypothesized to be a syndrome of chronic low serotonin (5-HT) levels, but investigations of brain 5-HT levels have given equivocal results. Here, we used positron emission tomography (PET) imaging of the 5-HT4 receptor as a proxy for brain 5-HT levels. Given that the 5-HT4 receptor is inversely related to brain 5-HT levels, we hypothesized that between attacks migraine patients would have higher 5-HT4 receptor binding compared to controls. Eighteen migraine patients without aura (migraine free >48 h), and 16 age- and sex-matched controls underwent PET scans after injection of [11C]SB207145, a specific 5-HT4 receptor radioligand. An investigator blinded to group calculated a neocortical mean [11C]SB207145 binding potential (BPND). Three migraine patients reported a migraine attack within 48 h after the scan and were excluded from the primary analysis. Comparing 15 migraine patients and 16 controls, we found that migraine patients have significantly lower neocortical 5-HT4 receptor binding than controls (0.60 ± 0.09 vs. 0.67 ± 0.05, p = .024), corrected for 5-HTTLPR genotype, sex and age. We found no association between 5-HT4 receptor binding and attack frequency, years with migraine or time since last migraine attack. Our finding of lower 5-HT4 receptor binding in migraine patients is suggestive of higher brain 5-HT levels. This is in contrast with the current belief that migraine is associated with low brain 5-HT levels. High brain 5-HT levels may represent a trait of the migraine brain or it could be a consequence of migraine attacks.

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