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Migraines, Cluster Headaches Associated With Circadian System
Cluster headaches and migraines were associated with the circadian system, according to a recent systematic review and meta-analysis in the journal Neurology.
“These results raise the potential for using circadian-based treatments for headache disorders,” said study author Mark Joseph Burish, MD, PhD, University of Texas Health Science Center at Houston in a news release. “This could include both treatments based on the circadian rhythm—such as taking medications at certain times of the day—and treatments that cause circadian changes, which certain medications can do.”
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Researchers sourced studies from medical databases including Medline Ovid, Embase, PsycINFO, Web of Science, and Cochrane Library, then 2 researchers independently conducted the systematic review/meta-analysis while following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. A separate genetic analysis was conducted to study the circadian pattern of expression in Clock Controlled Genes (CCGs) by cross-referencing genome-wide association studies (GWAS) of headache, a non-human primate study of CCGs in a variety of tissues, and recent reviews of brain areas relevant in headache disorders.
By combining the results of both studies, researchers were able to catalog the circadian features at different levels, including behavioral, systems, and cellular levels, providing a holistic understanding of the role of CCGs in headache disorders.
The meta-analysis found 1513 studies, 72 of which met inclusion criteria, while the genetic analysis found 16 GWAS, 1 non-human primate study, and 16 imaging reviews. Findings revealed significant differences between the circadian patterns of attacks in cluster headache and migraine.
In cluster headaches, a circadian peak was observed between 21:00 and 03:00, while in migraine, a circadian trough was observed between 23:00 and 07:00. The circannual peaks for cluster headache were observed in spring and fall, while migraine peaks were observed between April and October. The chronotype was highly variable across studies for both types of headaches. At the systems level, lower melatonin and higher cortisol levels were reported for cluster headache, while lower urinary melatonin levels were observed in migraine—even lower during an attack. At the cellular level, cluster headache was associated with core circadian genes CLOCK and REV-ERBα, and 5 of the 9 cluster headache susceptibility genes were CCGs. Conversely, migraine was associated with core circadian genes CK1δ and RORα, and 110 of the 168 migraine susceptibility genes were CCGs.
“This reinforces the importance of the hypothalamus—the area of the brain that houses the primary biological clock—and its role in cluster headache and migraine,” Dr Burish concluded. “It also raises the question of the genetics of triggers such as sleep changes that are known triggers for migraine and are cues for the body’s circadian rhythm.”
Authors noted that they did not have information on factors that may influence the circadian cycle, such as comorbid disorders or medications, which may have limited study findings.
