Migraine and Depression - Study Shows Allodynia Is a Factor

Teri Robert @trobert Health Guide
  • We know from earlier research that people with migraines tend to have a higher comorbidity rate of major depressive disorder (clinical depression.) A 2010 study by Terwindt et. al. concluded:

    "There is a bidirectional association between depression and Migraine, in particular Migraine with aura, which can be explained, at least partly, by shared genetic factors."2  (See Migraine and Depression May Be Linked Genetically.)

    In a new study, researchers set out to identify migraine-specific factors involved in the association between migraine and depression.

    The Study

    Study Objective:

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    "The aim of this study is to further elucidate the association between migraine and depression in a large, well-defined, web-based migraine cohort and to identify migraine-specific factors associated with depression."1

    Study Methods:

    • The study was conducted as a part of the Leiden University Migraine Neuro Analysis (LUMINA) project.
    • Participants of the LUMINA project were Dutch adults aged 18 to 74 years with migraine with or without aura according to the International Classification of Headache Disorders criteria (previously ICHD-II, now ICHD-3 beta version).
    • The LUMINA project was approved by the medical ethics committee of the Leiden University Medical Centre.
    • All subjects provided written informed consent prior to the study.
    • 3,624 migraineurs within the LUMINA project were sent a depression questionnaire
      (mean age: 41.7 11.9) based on migraine diagnosis.
    • 3,177 (87.7%) returned this depression questionnaire.
    • 2,533 were eventually included in the analysis because the questionnaires of the others were incomplete.

    Study Results:

    • Of the 2,533 eligible migraineurs who participated in the study, 1,137 (45%) experienced lifetime depression.
    • Of the 2,533 eligible migraineurs who participated in the study, 1,767 (70%) experienced allodynia (a condition in which an ordinarily painless stimulus is experienced as being painful) during migraine attacks.
    • Significant associations with depression were found for several migraine-specific variables, including:
      • attack frequency,
      • number of migraine days,
      • use of preventive medication, and
      • allodynia
    • Significant associations with depression were found for several variables that were not migraine-specific:
      • poor quality sleep, sleep disturbances;
      • gender (female);
      • body mass index (BMI) (higher);
      • level of education (lower);
      • marital status (being single);
      • smoking; and
      • low alcohol consumption.

    Study Conclusion:

    "This study identified allodynia, in addition to high migraine attack frequency, as a new migraine-specific factor associated with depression."1

    Clinical Implications of the Study:

    "A high attack frequency, allodynia (the experience of pain due to stimuli that do normally not provoke pain) and sleeping problems are associated with a higher prevalence of depression in migraine patients."1

    Summary and Comments:

    Perhaps the most important statement in this study is:


    "Pathophysiologically, the triad migraine, depression and allodynia may suggest a self-reinforcing dysfunction of central nervous system (CNS) structures involved in the modulation of neuronal excitability and pain."1


  • This statement strikes me as being especially important because, at this time, the best theory is that migraine disease is caused by genetics and an overly sensitive nervous system (neuronal excitability).

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    This study was large enough to be significant in and of itself. Since we still know too little about the pathophysiology of migraine, each discovery of significance, such as this one, contributes a bit more.


    1 Louter, MA; Wardenaar, KJ; Veen, G.; van Oosterhout, WPJ; Zitman, FG; Ferrari, MD; and Terwindt, GM. "Allodynia is associated with a higher prevalence of depression in migraine patients." Cephalalgia. Online First.  first published on April 25, 2014, as doi:10.1177/0333102414532554.

    2 Stam, A.H., MD; de Vries, B., MSC; Janssens, A.C.J.W., PhD; Vanmolkot, K.R.J., PhD; Aulchenko, Y.S.; PhD; Henneman, P., MSc; Oostra, B.A., PhD; Frantz, R.R., PhD; van den Maagdenberg, A.M.J.M., PhD; Ferrari, MD, PhD; van Duijn, C.M., PhD; Terwindt, G.M., MD, PhD. "Shared genetic factors in migraine and depression." Neurology® 2010;74:288–294.

    Live well,

    PurpleRibbonTiny Teri1


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    Reviewed by John Claude Krusz, PhD, MD


    Page copy protected against web site content infringement by Copyscape© Teri Robert, 2014. Last updated May 8, 2014.

Published On: May 08, 2014