For quite some time, we've had research showing Migraine disease and depression to frequently be comorbid diseases -- occurring together, but neither causing the other. Whereas the prevalence of depression in the general population has been estimated at 17%, among Migraineurs, that figure jumps to a startling 47% in some studies. It has seemed obvious that there must be a link between the two diseases, but we didn't know what that link was.

Conversely, studies have shown patients with depression to have a higher prevalence of Migraine that patients without depression.

Additionally, it's been shown that Migraineurs with depression have a decreased quality of life and that comorbid depression is a risk factor for Migraine becoming chronic and for developing medication overuse headache.

Now, research shows that Migraine and depression may share a strong genetic component. The research is published in the January 13, 2010, online issue of Neurology®, the medical journal of the American Academy of Neurology.

"Genealogical information has shown them all to be part of a large extended family, which makes this type of genetic study possible." ~ Gisela M. Terwindt, MD, PhD, study author 3

The study

Study objective:

"To investigate the co-occurrence of Migraine and depression and assess whether shared genetic factors may underlie both diseases."1

Study methods:

  • The study participants were 2,652 participants of the Erasmus Rucphen Family genetic isolate study.*
  • Migraine was diagnosed using a validated three-stage screening method that included a telephone interview.

  • Symptoms of depression were assessed using the Center for Epidemiologic Studies Depression scale and the depression subscale of the Hospital Anxiety and Depression Scale (HADS-D).

  • The contribution of shared genetic factors in Migraine and depression was investigated by comparing heritability estimates for Migraine with and without adjustment for symptoms of depression, and by comparing the heritability scores of depression between Migraineurs and controls.

  • The control group was comprised of participants who

    • did not report severe headache
    • did not report visual aura symptoms
    • had never been diagnosed with Migraine by
    • never used specific antimigraine medication

Study results:

A total of 977 people had depression, with 25 percent of those with Migraine also having depression, compared to 13 percent of those without Migraine

  • 360 cases of Migraine disease were identified
  • Of those 360 cases:
  • 209 had Migraine without aura (MWOA)

  • 151 had Migraine with aura (MWA).

  • 25 percent of study participants with Migraine also had depression

  • 13 percent of the control group had depression

  • Depression was more frequent in Migraine with aura than in Migraine without aura.

  • For participants with both MWOA and MWA, the heritability was estimated at 56 percent, i.e., 56 percent of the trait is explained by genetic effects.

  • For Migraine with aura, the heritability was estimated at 96 percent. Terwindt commented, "This finding shows that Migraine with aura may be a promising avenue to search for Migraine genes."3

Study conclusions:

"There is a bidirectional association between depression and Migraine, in particular Migraine with aura, which can be explained, at least partly, by shared genetic factors... Identification of common genetic factors may significantly improve insight into the molecular basis of these common and highly disabling episodic brain disorders."1

Terwindt commented, This suggests that common genetic pathways may, at least partly, underlie both of these disorders, rather than that one is the consequence of the other"3

Summary and comments:

In an editorial accompanying this journal article, Ahn makes some quite interesting comments I'd like to share with you:

"This finding informs our understanding of the heritability of these 2 disorders and prompts us to make note of our Migraine patients' family histories of both headache and depression. Further, this hypothesis may lead to better therapeutic strategies when these disorders are present together...

... From a therapeutic perspective, they appear to be interdependent but not equivalent, as the successful treatment of the primary disorder appears to be critical to the treatment of the comorbid condition. Furthermore, the medications used to treat these conditions have a large overlap with each other. Such extensive overlap likely contributes to the unfortunate prevailing tendency to formulate treatment strategies for these disorders indistinctly. However, with a better understanding of these disorders, patients with Migraine could one day benefit from therapeutic strategies based on their distinct, as well as overlapping, pathophysiology...

...Thus, the authors address the important question of the apparent bidirectional link between Migraine and depression, using a genetically isolated population, and show new data supporting the presence of shared genetic factors between depression and Migraine in MA. Confirmation of this association would suggest that at least one pathophysiologic process could underlie both of these disabling disorders, with other processes contributing to the distinct features of each.2

Ahn's comment confirmation of the genetic association is well taken. As with any research, scientists will want to see confirming research from another study.

Still, this research does again confirm the high rate of comorbidity between Migraine disease and depression. It then goes on to perhaps answer the question many of us have long asked, "Why?" It's only been in fairly recent years that Migraine has been recognized as a genetic neurological disease. Put that together with this research, and it's easier to see that medical research is making progress in understanding Migraine better. That understanding must advance if we're to have better treatments.

I close with another quote from Ahn, one which points to the true importance of this research:

"Understanding the genetic factors that contribute to these disabling disorders could one day lead to better strategies to manage the course of these diseases when they occur together. In the meantime, people with Migraine or depression should tell their doctors about any family history of either disease to help us better understand the link between the two." ~ Andrew Ahn, MD, PhD3

  • The study involved 2,652 people who took part in the larger Erasmus Rucphen Family study. All of the participants are descendants of 22 couples who lived in Rucphen in the 1850s to 1900s.


1 Stam, A.H., MD; de Vries, B., MSC; Janssens, A.C.J.W., PhD; Vanmolkot, K.R.J., PhD; Aulchenko, Y.S.; PhD; Henneman, P., MSc; Oostra, B.A., PhD; Frantz, R.R., PhD; van den Maagdenberg, A.M.J.M., PhD; Ferrari, MD, PhD; van Duijn, C.M., PhD; Terwindt, G.M., MD, PhD. "Shared genetic factors in migraine and depression." Neurology® 2010;74:288-294.

2 Ahn, Andrew H., MD, PhD; Ashizawa, Tetsuo, MD. "Headaches and the Blues." Neurology® 2010;74:278-279.

3 Press Release. "Migraine and Depression May Share Genetic Component." American Academy of Neurology. St. Paul. January 13, 2010.

Medical review by John Claude Krusz, PhD, MD