Unraveling the genetic architecture of migraine: exploring the vascular components

Abstract

This thesis explores the genetic causes and biological mechanisms underlying migraine and rare hereditary disorders that affect, among other things, the small blood vessels in the brain. The goal was to improve our understanding of these diseases, identify more targeted treatment options, and discover biomarkers that can help predict disease progression.

The first part focuses on migraine, a common neurological disorder. The research examined both genetic and epigenetic factors—meaning how gene activity is regulated—that may influence treatment response. The frequent co-occurrence of migraine with conditions such as epilepsy, stroke, and depression suggests shared underlying mechanisms, which can help guide therapy choices. Additionally, the thesis investigated rare genetic forms of migraine and found that certain medications may be more or less effective in these specific groups.

The second part studies rare hereditary small vessel diseases of the brain, including RVCL-S, CADASIL, and D-CAA. These diseases serve as models for understanding migraine and small vessel damage. Eye scans revealed abnormalities before the onset of symptoms, suggesting potential for early detection through imaging. In RVCL-S, MRI abnormalities were linked to cognitive decline, especially in patients over 50.

The final part addresses gender inequality and harassment in headache research. Globally, women and researchers from certain regions face more career obstacles. The thesis calls for a safer, more inclusive academic and clinical environment.