Are Migraines and PTSD Linked?

Genes may hold the answer to the puzzling comorbidity of migraines and posttraumatic stress disorder.

A new study in Frontiers in Neuroscience investigated the genetic basis for both migraine and posttraumatic stress disorder (PTSD) by examining identical twins.1 Researchers discovered there are common genes and pathways shared by PTSD and migraine, which may suggest they share some risk factors, thus in part explaining the comorbidity of the 2 conditions.

“Our results suggest that common genes and signaling pathways are involved in PTSD and migraine and this might explain why PTSD and migraine can cooccur frequently,” said senior author on the study, Divya Mehta, PhD, of the Queensland University of Technology. “This might further imply that common environmental risk factors for both PTSD and migraine might be acting on these genes.”2

The study observed 6 pairs of monozygotic (MZ) twins discordant for PTSD and 15 pairs of MZ twins discordant for migraine. PTSD was measured through phone interviews conducted by an experienced interviewer using structured questions and DSM-IV criteria. All 6 pairs of twins were identified as having experienced a PTSD-qualifying potentially traumatic event as per the DSM-IV criteria. Migraine was assessed using the International Headache Society (IHS) diagnostic criteria, the International Classification of Headache Disorders, ICHD-3, together with a diagnosis of migraine with or without aura. Pairs of twins discordant for migraine with aura were chosen for the study.

Blood samples were taken from all participants. Association between DNA methylation and PTSD status was tested using linear mixed effects models with age, sex, and cell counts as covariates. Using the same study design as the PTSD sample of twins, the 15 pairs of MZ twins discordant for migraine were tested for association of methylation at genetic loci that overlap between PTSD and migraine using varied analyses.

At the epigenome-wide level, researchers assessed how many of the 1036 genes associated with PTSD overlapped with those significantly associated with migraine in the discordant migraine MZ twins.

“We identified DAPK2 and TM6SF2 as two of the top overlapping genes between the two disorders. DAPK2 is a calmodulin-regulated protein kinase, it has been implicated in the intracellular degradation process essential for adaptation to metabolic stress (autophagy). TM6SF2 is associated with cardiovascular disease and plays a role in oxidative stress. These findings suggest that epigenetic changes in response to different types of stress may ‘mediate’ stress phenotypes,” said the study’s authors.1

The findings could form the basis for new treatments. Epigenetic changes offer an excellent drug target, as they can often be reversed.

“These results may have implications for treatments, as one medicine or therapy might only be effective for a single disorder,” said Mehta. “For co-occurring disorders such as PTSD and migraine, once we know which common genes are implicated in both disorders, we can develop new therapeutics to target these, thereby reducing symptoms and curing both.”

References

1. Bainomugisa CK, Sutherland H, Parker R, et al. Using monozygotic twins to dissect common genes in posttraumatic stress disorder and migraine. Frontiers in Neuroscience. June 22, 2021. https://doi.org/10.3389/fnins.2021.678350

2. Frontiers. Twin study is first to reveal common genetic risk factors for PTSD and migraine. News release. June 22, 2021. https://blog.frontiersin.org/2021/06/22/neuroscience-twins-genes-risk-ptsd-migraine/