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2015 MRF Research Grantee
FINAL REPORT: Investigation of the serotonergic system in the migraine brain using positron emission tomography
Serotonin has for decades been highlighted as a key neurotransmitter in migraine pathophysiology, and it has been hypothesized that migraine is a chronic low serotonin syndrome. However, studies of brain serotonin levels in migraine have so far given conflicting results. Here we investigated brain serotonin levels in episodic and chronic migraine patients using PET imaging of the 5-HT4 receptor. The 5-HT4 receptor is inversely related to brain serotonin levels and can therefore be used as an indicator of serotonin levels. We hypothesized that migraine patients would have higher 5-HT4 receptor binding (lower brain serotonin levels) than controls. We also hypothesized that migraine frequency would be related to brain 5-HT4 receptor binding, such that increasing migraine frequency would result in higher binding and lower brain serotonin levels. We investigated 15 episodic and 16 chronic migraine patients and found that compared to the 16 controls, all migraine patients had higher serotonin levels. We also found that migraine frequency was not related to brain serotonin levels.
Hypothesis vs. Findings
Based on previous studies, we hypothesized that episodic migraine patients would have lower brain serotonin levels compared to controls. However, using an advanced neuroimaging technique, we found that episodic migraine patients actually had higher levels than controls. After these findings, we adjusted our hypothesis for chronic migraine patients. Instead of expecting lower brain serotonin levels compared to controls and to episodic migraine patients, we then expected to find higher levels. Our revised hypothesis was confirmed with the finding of lower binding (higher brain serotonin levels) in chronic migraine compared to controls. We found that both episodic and chronic migraine patients had higher levels than controls. However, we found no association between brain serotonin levels and migraine frequency.
Our studies in migraine patients showed that brain serotonin levels could not be used as a biomarker for conversion from episodic into chronic migraine. High levels might, however, be used as a biomarker of the migraine brain. To what extent high brain serotonin levels could contribute to the susceptibility to migraine attacks remains unknown and should be addressed in future studies.
What this Research Means to You
Our findings suggest that increased brain serotonin levels may be a fundamental condition of the migraine brain.