Adverse Childhood Experiences Are Associated With Migraine and Vascular Biomarkers

Authors

  • Gretchen E. Tietjen MD,

    Corresponding author
    1. From the Department of Neurology, University of Toledo, Toledo, OH, USA (G.E. Tietjen); Department of Physiology and Health Science, Global Health Institute, Ball State University, Muncie, IN, USA (J. Khubchandani); University of Toledo Medical Center, Toledo, OH, USA (N.A. Herial and K. Shah)
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  • Jagdish Khubchandani MBBS, PhD, MPH,

    1. From the Department of Neurology, University of Toledo, Toledo, OH, USA (G.E. Tietjen); Department of Physiology and Health Science, Global Health Institute, Ball State University, Muncie, IN, USA (J. Khubchandani); University of Toledo Medical Center, Toledo, OH, USA (N.A. Herial and K. Shah)
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  • Nabeel A. Herial MD, MPH,

    1. From the Department of Neurology, University of Toledo, Toledo, OH, USA (G.E. Tietjen); Department of Physiology and Health Science, Global Health Institute, Ball State University, Muncie, IN, USA (J. Khubchandani); University of Toledo Medical Center, Toledo, OH, USA (N.A. Herial and K. Shah)
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  • Kavit Shah BS

    1. From the Department of Neurology, University of Toledo, Toledo, OH, USA (G.E. Tietjen); Department of Physiology and Health Science, Global Health Institute, Ball State University, Muncie, IN, USA (J. Khubchandani); University of Toledo Medical Center, Toledo, OH, USA (N.A. Herial and K. Shah)
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  • Conflict of Interest: Dr. Tietjen has received grant support for the biomarker studies from GSK. Dr. Khubchandani has received faculty development research funds from the Global Health Institute at Ball State University. Dr. Herial reports no disclosures. Mr. Shah reports no disclosures.

  • Authors’ Contributions: Gretchen Tietjen, MD, provided the overall leadership and oversight to the study. She was the main designer of the study. She also supervised the research team, provided critical input on data analysis, and served as chief writer and editor of the manuscript. Jagdish Khubchandani, MBBS, PhD, helped conceive the idea for this research, and managed the data collection process. He contributed significantly to data analysis, writing of the results, and critical editing of the manuscript. Nabeel Herial, MD, enrolled subjects in the original study, and collected and compiled the demographic and biomarker database. He also helped edit and write the manuscript. Kavit Shah, MS, prepared and assembled the mailings and monitored the returns for the survey study. He assisted with writing the review of literature.

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G.E. Tietjen, Department of Neurology, University of Toledo, 3000 Arlington Avenue, MS 1195, Toledo, OH 43614, USA, email: gretchen.tietjen@utoledo.edu

Abstract

Objectives.— 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.

Methods.— 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).

Results.— 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).

Conclusions.— 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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