TY - JOUR

T1 - High brain serotonin levels in migraine between attacks

T2 - A 5-HT4 receptor binding PET study

AU - Deen, Marie

AU - Hansen, Hanne D.

AU - Hougaard, Anders

AU - Nørgaard, Martin

AU - Eiberg, Hans

AU - Lehel, Szabolcs

AU - Ashina, Messoud

AU - Knudsen, Gitte M

PY - 2018

Y1 - 2018

N2 - 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.

AB - 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.

U2 - 10.1016/j.nicl.2018.01.016

DO - 10.1016/j.nicl.2018.01.016

M3 - Journal article

C2 - 29387527

VL - 18

SP - 97

EP - 102

JO - NeuroImage: Clinical

JF - NeuroImage: Clinical

SN - 2213-1582

ER -