Shared Genetics May Underly Co-Occurring Migraine, Depression

Migraine and depression commonly co-occur, and the comorbidity is associated with worse quality of life, higher rates of disability, and worse health outcomes compared to healthy controls or individuals with only one of the disorders. According to a 2011 review,¹ depression occurs nearly twice as often in people with migraine vs headache-free people, and longitudinal studies have found a bidirectional link in which having one disorder increases the risk of having the other. 

A new study published in Twin Research and Human Genetics investigated a potential shared genetic basis underlying the migraine-depression connection in 5319 twin pairs (2456 monozygotic and 2863 dizygotic).²

Researchers at Queensland University of Technology and QIMR Berghofer Medical Research Institute in Australia, and Washington University School of Medicine in St. Louis, Missouri, used 1 of 3 measures to classify migraine: self-report, the ID migraine™ screener, or the International Headache Society (IHS) diagnostic criteria for migraine without aura (MO) and migraine with aura (MA). Depression was classified according the Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria for major depressive disorder (MDD) and minor depressive disorder (MiDD). A status of “broad” migraine was assigned for participants with any measure of migraine, while a “narrow” status was limited to the IHS clinical diagnosis. For depression, a broad status was applied for participants with either MiDD or MDD, and the MDD diagnosis qualified as the narrow status.

Results showed that the estimated univariate heritability of broad migraine was 56% (95% confidence interval [CI]: 53–60%), and for broad depression, approximately 42% (95% CI: 37–46%). Additionally, a bivariate heritability and additive genetic correlation were found between broad migraine and depression, and these increased when the analysis was limited to MDD and the clinical IHS migraine diagnosis (from h2 = 5.5%, 95% CI: 3.6–7.8% to h2 =13.3%, 95% CI: 7.0–24.5%, and rG = 0.36, 95% CI: 0.29–0.43 to rG =0.51, 95% CI: 0.37–0.69, respectively). Heritability estimates for migraine and depression increased as the severity of the disorders increased. No sex-specific effects on migraine and depression risk were observed. 

These findings suggest that “the observed comorbidity between migraine and depression can be explained by a shared etiology (rather than a causal relationship) that almost entirely comprises shared underlying genetically determined disease mechanisms,” the authors concluded. These are consistent with results of numerous previous studies and could have implications for the ultimate discovery of novel pathways and treatments.

References

1. Antonaci F, Nappi G, Galli F, Manzoni GC Calabresi P, Costa A. Migraine and psychiatric comorbidity: a review of clinical findings. J Headache Pain. 2011; 12(2): 115–125.
2. Yang Y, Zhao H, Heath AC, Madden PA, Martin NG, Nyholt DR. Shared Genetic Factors Underlie Migraine and Depression. Twin Res Hum Genet. 2016; 19(4):341-50.