Genetic link to migraines

A genetic cause for migraines has been discovered by scientists in America.

Affecting up to 15% of the population, and more women than men, migraines are a common neurological condition. Patients usually suffer severe headaches, which can be accompanied by an aura or sensory disturbances such as seeing flashing lights, numbness on one side of the body, or hearing strange sounds.

But our understanding of migraines is limited because it's likely that this is not a single condition with a single cause. Instead scientists suspect that migraines may be the end result of a range of different underlying conditions. But by understanding how they occur, it should be possible to gain insights into the underlying mechanisms.

Now, University of California, San Francisco scientist Louis Ptácek and his colleagues, writing in Science Translational Medicine, used genetic sequencing techniques to identify a faulty gene in two families that suffer from migraines.

The families in question also suffered from a rare second type of condition, familial advanced sleep phase syndrome, or FASPS, a sleep disorder in which people are sleepy early in the evening and suffer insomnia in the early morning. But, remarkably, the gene - casein kinase Iδ or CKIδ - that causes FASPS may also cause migraines.

By introducing a copy of the faulty gene found in the families into mice, the scientists discovered that animals were more sensitive to heat and touch, similar to the sensory sensitivity seen in humans during migraine attacks. The mice were also more likely to display a phenomenon called "cortical spreading depression" or CSD, in which the brain cells fire powerful waves of electrical impulses. Moreover, this effect appeared to be linked to increased dilatation of blood vessels in the brain, one of the mechanisms believed to be behind the symptoms of migraines.

But why do changes to the CKIδ gene give migraine-like symptoms? Previous studies have shown that CKIδ interacts with proteins called connexins, found in astrocytes, which are the star-shaped cells that link neurons with blood vessels in the brain. Connexins are structural proteins that electrically couple brain cells together and it is believed that mutating the CKIδ gene reduces its interaction with connexins and, in turn, increasing the spontaneous activity of astrocytes. This change in brain cell signalling leads to increased vasodilatation and thus the debilitating symptoms of migraine.

These findings suggest that, apart from regulating the body clock, these same genes may also play a role in migraine. As the authors acknowledge in their paper, these findings may not represent the causative factor for all migraines, but they do contribute to our understanding of the genetics of migraines and the link between migraines and sleep.