Patients with migraine headaches are at greater risk for major depressive disorder (MDD), and a recent review published in Cureus suggests that the strong relationship between the conditions may be explained by a robust molecular genetic background.1

Migraine headache and MDD are common debilitating disorders that may have a significant impact on patients’ quality of life.2 Studies have shown that MDD is associated with poor academic performance, decreased productivity, and poor appetite and sleep.1

Significant Links

In a prospective study to examine the association between migraine and depression, Tietjen and colleagues reported that among women with chronic headache, the prevalence rate of MDD was 29 percent. The risk for MDD was 25 times greater among patients with chronic headache, very severe headache-related disability, and high somatic symptom severity, compared with patients without any of these conditions.3

Amiri and colleagues completed a literature search and a meta-analysis that included 16 eligible articles. They reported that migraine headaches can nearly double the risk for depression.4 On the other hand, depression was significantly associated with an increased risk for chronic migraine.5

Genes or Environment?

Some data suggest that migraine pathophysiology involves heritable and environmental components. Family history of migraine is very common in patients with migraine, and studies conducted for migraine and MDD showed a moderate heritability with an estimated heritability of 30 to 50 percent between both conditions.

Several previous studies, including twin- and family-based studies, reported that both migraine and depression have a strong genetic basis and both diseases share molecular pathways controlling serotonergic and glutaminergic neurotransmitter system.6

Several inflammatory markers, including interleukin-1 beta, interleukin-6, tumor necrosis factor-alpha, and high sensitivity C-reactive protein, were found to be increased in patients with depression.1,7

A comprehensive analysis to determine the genetic overlap between MDD and migraine and to identify shared genetic factors between the 2 conditions at the molecular level has shown a significant overlap at both the single nucleotide polymorphism and gene level. Genome-wide association studies identified 3 single nucleotide polymorphisms (rs146377178, rs672931, and rs11858956) associated with migraine and MDD; gene-based association analyses revealed 2 genome-wide significant genes, including ankyrin repeat and death domain containing 1A (ANKDD1B) and potassium channel, subfamily K, member 5 (KCNK5).8


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