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Childhood Adversity Is Associated With Migraine and Biomarkers of Inflammation

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Childhood adversity, including abuse, neglect, and exposure to household dysfunction, is associated with migraine and biomarkers of inflammation, coagulation, and oxidative stress in premenopausal women, according to research published in the April 25 online issue of Headache.

Approximately 71% of migraineurs reported having experienced childhood adversity, compared with 46% of controls. Average scores on a survey of adverse childhood experiences (ACEs) were higher among patients with migraine than among controls. Among migraineurs, ACE scores were higher for patients with chronic, continuous, and transformed migraine.

Women who reported adversity were more likely to have biomarkers indicating coagulation, such as elevated von Willebrand factor activity, said Gretchen E. Tietjen, MD, Professor and Chair of Neurology at the University of Toledo in Ohio. Biomarkers indicating inflammation (eg, elevated high-sensitivity C-reactive protein) and oxidative stress (eg, low nitrite concentration) also were more frequent among women reporting adversity.

Using International Criteria to Assess the Link Between Adversity and Migraine
Migraine, which is a risk factor for stroke, previously has been associated with biomarkers of oxidative stress, coagulation, and inflammation, which are risk markers for ischemia. Dr. Tietjen and her colleagues performed a study to determine whether ACEs were linked to migraine as well as these specific biomarkers.

Between February 2006 and October 2008, the researchers recruited 175 premenopausal women between the ages of 18 and 50. Of these participants, 125 had been diagnosed with migraine, as defined by the International Headache Classification, and 50 were controls. Through a questionnaire, all participants provided information such as age, education, income, age of headache onset, headache-related disability, and physician-diagnosed medical conditions. The researchers took blood and urine samples from the participants and analyzed them for various biomarkers.

In November 2010, the researchers mailed a questionnaire about ACEs to the participants. The one-page questionnaire, which had been used in several studies, solicited information about the participants’ exposure to abuse, neglect, and household dysfunction. Questionnaires were returned by 100 patients with migraine and by 41 controls.

Childhood Adversity Is Associated With Various Comorbidities
After stratifying the study population by presence or absence of ACE, the researchers found that participants reporting adversity were more likely to have low income, less education, high BMI, history of hypertension, and current smoking. Most of the associations between adversity and biomarkers remained significant after the investigators adjusted for age, education, and stroke risk factors. In addition, the association of childhood ACEs with inflammatory factors remained significant after adjusting for migraine.

“In persons with migraine, a history of early-life adversity may foreshadow the development of other related conditions, particularly those tied to inflammation,” Dr. Tietjen told Neurology Reviews. “Research is needed to gain a better understanding of the mechanism by which adverse childhood experiences are associated with migraine and with inflammatory markers,” she continued. “I am also interested in whether the increased incidence of stroke in young female migraineurs without traditional risk factors can in any way be explained by adversity-related changes in the hypothalamic–pituitary–adrenal stress axis and immune system. The most intriguing area of inquiry for me as a clinician is to discover therapies that prevent the adverse effects that early abuse has been shown to have on a wide range of health outcomes,” Dr. Tietjen concluded.


—Erik Greb

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