Post-traumatic stress disorder (PTSD) and migraine often co-occur, but researchers know relatively little about how or why this happens. Now, researchers from Australia along with colleagues from the United States published a new study (“Using Monozygotic Twins to Dissect Common Genes in Posttraumatic Stress Disorder and Migraine”) that reportedly is the first to investigate if the conditions have a common genetic basis.

By studying identical twins, where one twin in each pair lives with PTSD or migraines and the other twin does not, the researchers found common genes that may play a role in both conditions. These genes may help to explain why the conditions co-occur, and could reveal new treatment targets for both.

PTSD is a psychiatric disorder that typically occurs after a traumatic experience, such as a life-threatening event. Most people will experience a traumatic event at some point in their lives, but the vast majority will not develop PTSD, so there is something special about those who do.

Those who live with PTSD are also more likely to experience migraine headaches, suggesting common risk factors for these conditions. The synergy between PTSD and migraines is not understood as no studies have examined this link before. This latest study suggests that our genes may hold the answer, and specifically, epigenetic changes.

The researchers focused on epigenetics in twins to see which genes show altered activity in PTSD and migraine and whether the conditions shared common changes. Six pairs of twins volunteered for the study, where both twins had experienced traumatic events, but only one of each pair lives with PTSD.

Small sample size but powerful study

Given the low probability that all these conditions are met, the sample size could never be large. But because identical twins share all of their DNA, but not all of their epigenetic marks, the study is still powerful. The researchers also enrolled 15 pairs of twins where one of each pair experiences migraine headaches. The researchers took blood samples from the twins and analyzed them to detect epigenetic changes associated with PTSD or migraine.

“Epigenetic mechanisms have been associated with genes involved in PTSD. PTSD often co-occurs with other health conditions such as depression, cardiovascular disorder, and respiratory illnesses. PTSD and migraine have previously been reported to be symptomatically positively correlated with each other, but little is known about the genes involved,” wrote the investigators.

“The aim of this study was to understand the comorbidity between PTSD and migraine using a monozygotic twin disease discordant study design in six pairs of monozygotic twins discordant for PTSD and 15 pairs of monozygotic twins discordant for migraine. DNA from peripheral blood was run on Illumina EPIC arrays and analyzed. Multiple testing correction was performed using the Bonferroni method and 10% false discovery rate (FDR).

“We validated 11 candidate genes previously associated with PTSD, including DOCK2, DICER1, and ADCYAP1. In the epigenome-wide scan, seven novel CpGs were significantly associated with PTSD within/near IL37, WNT3, ADNP2, HTT, SLFN11, and NQO2, with all CpGs except the IL37 CpG hypermethylated in PTSD. These results were significantly enriched for genes whose DNA methylation was previously associated with migraine (p-value = 0.036).

“At 10% FDR, 132 CpGs in 99 genes associated with PTSD were also associated with migraine in the migraine twin samples. Genes associated with PTSD were overrepresented in vascular smooth muscle, axon guidance and oxytocin signaling pathways, while genes associated with both PTSD and migraine were enriched for AMPK signaling and longevity regulating pathways.

“In conclusion, these results suggest that common genes and pathways are likely involved in PTSD and migraine, explaining at least in part the co-morbidity between the two disorders.”

Key findings

The study revealed that certain genes are similarly affected in PTSD and migraine, suggesting that they may share some risk factors.

“Our results suggest that common genes and signaling pathways are involved in PTSD and migraine and this might explain why PTSD and migraine can co-occur frequently,” explained Divya Mehta, PhD, associate professor and principal research fellow, at the Queensland University of Technology and senior author on the study. “This might further imply that common environmental risk factors for both PTSD and migraine might be acting on these genes.”

So, what do these findings mean for those living with PTSD and/or migraines? Well, the genes and epigenetic modifications the researchers identified 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.”

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