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Headache. 2012 Jun;52(6):920-9. doi: 10.1111/j.1526-4610.2012.02165.x. Epub 2012 Apr 25.

Adverse childhood experiences are associated with migraine and vascular biomarkers.

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  • 1Department of Neurology, University of Toledo, 3000 Arlington Avenue, Toledo, OH 43614, USA.



Migraine is a risk factor for stroke in young women. Biomarker studies implicate endothelial activation as a possible mechanism. Emerging relationships of childhood adversity with migraine, and with inflammation, a component of endothelial activation, suggest that it may play a role in the migraine-stroke association. Our objective is to evaluate the relationship between adverse childhood experiences (ACEs), migraine, and vascular biomarker levels in premenopausal women.


Vascular and metabolic biomarkers from women 18-50 years, including 125 with migraine (interictal) and 50 without migraine, were evaluated. An ACE questionnaire was later collected by mail (response rate 80.6%, 100 migraineurs, 41 controls).


Migraineurs and controls were demographically similar. Migraineurs reported adversity more commonly than controls (71% vs 46%, odds ratio [OR] = 1.53, 95% confidence interval 1.07-2.17). Average ACE scores were elevated in migraineurs as compared with controls (2.4 vs 0.76, P < .001). ACE scores correlated with headache frequency (0.37, P = .001) and younger age of headache onset (-0.22, P = .04). It also correlated with body mass index (r = 0.43, P = .0001), von Willebrand factor activity (r = 0.21, P = .009), tissue plasminogen activator antigen (r = 0.28, P = .004), prothrombin activation fragment (r = 0.36, P = .001), high-sensitivity C-reactive protein (r = 0.98, P = .0001), transforming growth factor-beta1 (r = 0.28, P = .003), tissue necrosis factor-alpha (r = 0.20, P = .03), interleukin-6 (r = 0.22, P = .03), adiponectin (r = -0.29, P = .003), and nitrate/nitrite concentration (r = -314, P = .001). Logistic regression analyses (adjusted for vascular risk factors and migraine) demonstrated an association of childhood adversity with inflammatory factors (high-sensitivity C-reactive protein, interleukin-6, and tissue necrosis factor-alpha).


In young women, adverse childhood events are associated with migraine, particularly chronic and transformed migraine, and with vascular biomarkers, especially inflammatory biomarkers. These findings implicate early life stress as a link between migraine and endothelial activation.

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