Causal relationship between primary headache mediated by circulating cytokines and cerebral cortex structure: a...

Area of Science:

• Neuroscience
• Genetics
• Inflammation Research

Background:

• Inflammation is implicated in cerebral cortex structural changes.
• The role of cytokines in mediating the link between brain structure and primary headaches remains unclear.

Purpose of the Study:

• To investigate if cytokines mediate the relationship between structural brain changes and primary headaches, specifically migraine, cluster headache, and tension-type headache.
• To identify specific cytokines involved in these associations.

Main Methods:

• Utilized summary statistics from genome-wide association studies (GWAS) for primary headaches (migraine, cluster headache, tension-type headache).
• Analyzed genome-wide pQTL mapping data for 91 cytokines.
• Employed Mendelian randomization (MR) analysis (IVW, MR-Egger, weighted median) using GWAS data for cortical surface area (SA) and thickness (TH) from the ENIGMA Consortium.

Main Results:

• Migraine was associated with reduced paracentral SA mediated by fibroblast growth factor-23 (FGF-23).
• Migraine was linked to reduced superior parietal thickness mediated by interleukin (IL)-15RA.
• Migraine without aura showed an association with reduced rostral anterior cingulate thickness mediated by IL-18R1.

Conclusions:

• Fibroblast growth factor-23 (FGF-23) and IL-15RA are associated with reduced cortical surface area or thickness in migraine patients.
• IL-18R1 is associated with increased cortical thickness in migraine without aura.
• These findings suggest specific cytokines mediate structural brain alterations in primary headaches.