Exploring the Link Between Migraine and PTSD

Psychiatric Times, Vol 38, Issue 12,

Are common genes and signaling pathways involved in PTSD and migraine?

Previous studies have found links between migraine and other psychiatric disorders, including bipolar disorder, peripartum depression, and attention-deficit/hyperactivity disorder.1-3 Now, research points to a common genetic basis for both migraine and posttraumatic stress disorder (PTSD).4 The results further suggest shared risk factors, thus partially explaining the comorbidity of these 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 co-occur 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.”5

The study observed 6 pairs of monozygotic (MZ) twins discordant for PTSD and 15 pairs of MZ twins discordant for migraine. PTSD was assessed via 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 International Headache Society diagnostic criteria (International Classification of Headache Disorders, Third Edition) 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,” the study authors explained.4

“To the best of our knowledge, this is the first study to examine overlapping genes and biological processes in PTSD and migraine comorbidity using the monozygotic co-twin design,” the authors reported. “These results are important and suggest that common genes and pathways might be associated with PTSD and migraine, with implications for diagnosis of comorbidities in PTSD and common treatments for these comorbid disorders.”

“These results may have implications for treatments, as one medicine or therapy might only be effective for a single disorder,” Mehta added. “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.”


1. Duan J, Yang R, Lu W, et al. Comorbid bipolar disorder and migraine: from mechanisms to treatment. Front Psychiatry. 2021;11:560138. Accessed October 27, 2021.

2. Welander NZ, Mwinyi J, Asif S, et al. Migraine as a risk factor for mixed symptoms of peripartum depression and anxiety in late pregnancy: a prospective cohort study. J Affect Disord. 2021;295:733-739.

3. Folkmann Hansen T, Hoeffding LK, Kogelman L, et al. Comorbidity of migraine with ADHD in adults. BMC Neurol. 2018;18(1):147. Accessed October 27, 2021.

4. 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. Accessed October 27, 2021.

5. Hastings C. Twin study is first to reveal common genetic risk factors for PTSD and migraine. Frontiers Science News. June 22, 2021. Accessed October 27, 2021. ❒