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June 04, 2013; 80 (23) Article

Migraine, depression, and brain volume

The AGES-Reykjavik Study

Larus S. Gudmundsson, Ann I. Scher, Sigurdur Sigurdsson, Mirjam I. Geerlings, Jean-Sebastien Vidal, Gudny Eiriksdottir, Melissa I. Garcia, Tamara B. Harris, Olafur Kjartansson, Thor Aspelund, Mark A. van Buchem, Vilmundur Gudnason, Lenore J. Launer
First published May 22, 2013, DOI: https://doi.org/10.1212/WNL.0b013e318295d69e
Larus S. Gudmundsson
From the Department of Preventive Medicine and Biometrics (L.S.G., A.I.S.), Uniformed Services University of the Health Sciences; Laboratory of Epidemiology, Demography and Biometry (L.S.G., A.I.S., M.I.G., J.-S.V., M.I.G., T.B.H., L.J.L.), National Institute on Aging, Bethesda, MD; Icelandic Heart Association (S.S., G.E., O.K., T.A., V.G.), Kopavogur, Iceland; University Medical Center Utrecht (M.I.G.), Julius Center for Health Sciences and Primary Care, Utrecht, the Netherlands; Université Paris Descartes (J.-S.V.), Sorbonne Paris Cité, Paris, France; Faculty of Medicine (T.A., V.G.), University of Iceland, Reykjavik, Iceland; and Department of Radiology (M.A.v.B.), Leiden University Medical Center, Leiden, the Netherlands.
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Ann I. Scher
From the Department of Preventive Medicine and Biometrics (L.S.G., A.I.S.), Uniformed Services University of the Health Sciences; Laboratory of Epidemiology, Demography and Biometry (L.S.G., A.I.S., M.I.G., J.-S.V., M.I.G., T.B.H., L.J.L.), National Institute on Aging, Bethesda, MD; Icelandic Heart Association (S.S., G.E., O.K., T.A., V.G.), Kopavogur, Iceland; University Medical Center Utrecht (M.I.G.), Julius Center for Health Sciences and Primary Care, Utrecht, the Netherlands; Université Paris Descartes (J.-S.V.), Sorbonne Paris Cité, Paris, France; Faculty of Medicine (T.A., V.G.), University of Iceland, Reykjavik, Iceland; and Department of Radiology (M.A.v.B.), Leiden University Medical Center, Leiden, the Netherlands.
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Sigurdur Sigurdsson
From the Department of Preventive Medicine and Biometrics (L.S.G., A.I.S.), Uniformed Services University of the Health Sciences; Laboratory of Epidemiology, Demography and Biometry (L.S.G., A.I.S., M.I.G., J.-S.V., M.I.G., T.B.H., L.J.L.), National Institute on Aging, Bethesda, MD; Icelandic Heart Association (S.S., G.E., O.K., T.A., V.G.), Kopavogur, Iceland; University Medical Center Utrecht (M.I.G.), Julius Center for Health Sciences and Primary Care, Utrecht, the Netherlands; Université Paris Descartes (J.-S.V.), Sorbonne Paris Cité, Paris, France; Faculty of Medicine (T.A., V.G.), University of Iceland, Reykjavik, Iceland; and Department of Radiology (M.A.v.B.), Leiden University Medical Center, Leiden, the Netherlands.
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Mirjam I. Geerlings
From the Department of Preventive Medicine and Biometrics (L.S.G., A.I.S.), Uniformed Services University of the Health Sciences; Laboratory of Epidemiology, Demography and Biometry (L.S.G., A.I.S., M.I.G., J.-S.V., M.I.G., T.B.H., L.J.L.), National Institute on Aging, Bethesda, MD; Icelandic Heart Association (S.S., G.E., O.K., T.A., V.G.), Kopavogur, Iceland; University Medical Center Utrecht (M.I.G.), Julius Center for Health Sciences and Primary Care, Utrecht, the Netherlands; Université Paris Descartes (J.-S.V.), Sorbonne Paris Cité, Paris, France; Faculty of Medicine (T.A., V.G.), University of Iceland, Reykjavik, Iceland; and Department of Radiology (M.A.v.B.), Leiden University Medical Center, Leiden, the Netherlands.
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Jean-Sebastien Vidal
From the Department of Preventive Medicine and Biometrics (L.S.G., A.I.S.), Uniformed Services University of the Health Sciences; Laboratory of Epidemiology, Demography and Biometry (L.S.G., A.I.S., M.I.G., J.-S.V., M.I.G., T.B.H., L.J.L.), National Institute on Aging, Bethesda, MD; Icelandic Heart Association (S.S., G.E., O.K., T.A., V.G.), Kopavogur, Iceland; University Medical Center Utrecht (M.I.G.), Julius Center for Health Sciences and Primary Care, Utrecht, the Netherlands; Université Paris Descartes (J.-S.V.), Sorbonne Paris Cité, Paris, France; Faculty of Medicine (T.A., V.G.), University of Iceland, Reykjavik, Iceland; and Department of Radiology (M.A.v.B.), Leiden University Medical Center, Leiden, the Netherlands.
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Gudny Eiriksdottir
From the Department of Preventive Medicine and Biometrics (L.S.G., A.I.S.), Uniformed Services University of the Health Sciences; Laboratory of Epidemiology, Demography and Biometry (L.S.G., A.I.S., M.I.G., J.-S.V., M.I.G., T.B.H., L.J.L.), National Institute on Aging, Bethesda, MD; Icelandic Heart Association (S.S., G.E., O.K., T.A., V.G.), Kopavogur, Iceland; University Medical Center Utrecht (M.I.G.), Julius Center for Health Sciences and Primary Care, Utrecht, the Netherlands; Université Paris Descartes (J.-S.V.), Sorbonne Paris Cité, Paris, France; Faculty of Medicine (T.A., V.G.), University of Iceland, Reykjavik, Iceland; and Department of Radiology (M.A.v.B.), Leiden University Medical Center, Leiden, the Netherlands.
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Melissa I. Garcia
From the Department of Preventive Medicine and Biometrics (L.S.G., A.I.S.), Uniformed Services University of the Health Sciences; Laboratory of Epidemiology, Demography and Biometry (L.S.G., A.I.S., M.I.G., J.-S.V., M.I.G., T.B.H., L.J.L.), National Institute on Aging, Bethesda, MD; Icelandic Heart Association (S.S., G.E., O.K., T.A., V.G.), Kopavogur, Iceland; University Medical Center Utrecht (M.I.G.), Julius Center for Health Sciences and Primary Care, Utrecht, the Netherlands; Université Paris Descartes (J.-S.V.), Sorbonne Paris Cité, Paris, France; Faculty of Medicine (T.A., V.G.), University of Iceland, Reykjavik, Iceland; and Department of Radiology (M.A.v.B.), Leiden University Medical Center, Leiden, the Netherlands.
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Tamara B. Harris
From the Department of Preventive Medicine and Biometrics (L.S.G., A.I.S.), Uniformed Services University of the Health Sciences; Laboratory of Epidemiology, Demography and Biometry (L.S.G., A.I.S., M.I.G., J.-S.V., M.I.G., T.B.H., L.J.L.), National Institute on Aging, Bethesda, MD; Icelandic Heart Association (S.S., G.E., O.K., T.A., V.G.), Kopavogur, Iceland; University Medical Center Utrecht (M.I.G.), Julius Center for Health Sciences and Primary Care, Utrecht, the Netherlands; Université Paris Descartes (J.-S.V.), Sorbonne Paris Cité, Paris, France; Faculty of Medicine (T.A., V.G.), University of Iceland, Reykjavik, Iceland; and Department of Radiology (M.A.v.B.), Leiden University Medical Center, Leiden, the Netherlands.
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Olafur Kjartansson
From the Department of Preventive Medicine and Biometrics (L.S.G., A.I.S.), Uniformed Services University of the Health Sciences; Laboratory of Epidemiology, Demography and Biometry (L.S.G., A.I.S., M.I.G., J.-S.V., M.I.G., T.B.H., L.J.L.), National Institute on Aging, Bethesda, MD; Icelandic Heart Association (S.S., G.E., O.K., T.A., V.G.), Kopavogur, Iceland; University Medical Center Utrecht (M.I.G.), Julius Center for Health Sciences and Primary Care, Utrecht, the Netherlands; Université Paris Descartes (J.-S.V.), Sorbonne Paris Cité, Paris, France; Faculty of Medicine (T.A., V.G.), University of Iceland, Reykjavik, Iceland; and Department of Radiology (M.A.v.B.), Leiden University Medical Center, Leiden, the Netherlands.
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Thor Aspelund
From the Department of Preventive Medicine and Biometrics (L.S.G., A.I.S.), Uniformed Services University of the Health Sciences; Laboratory of Epidemiology, Demography and Biometry (L.S.G., A.I.S., M.I.G., J.-S.V., M.I.G., T.B.H., L.J.L.), National Institute on Aging, Bethesda, MD; Icelandic Heart Association (S.S., G.E., O.K., T.A., V.G.), Kopavogur, Iceland; University Medical Center Utrecht (M.I.G.), Julius Center for Health Sciences and Primary Care, Utrecht, the Netherlands; Université Paris Descartes (J.-S.V.), Sorbonne Paris Cité, Paris, France; Faculty of Medicine (T.A., V.G.), University of Iceland, Reykjavik, Iceland; and Department of Radiology (M.A.v.B.), Leiden University Medical Center, Leiden, the Netherlands.
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Mark A. van Buchem
From the Department of Preventive Medicine and Biometrics (L.S.G., A.I.S.), Uniformed Services University of the Health Sciences; Laboratory of Epidemiology, Demography and Biometry (L.S.G., A.I.S., M.I.G., J.-S.V., M.I.G., T.B.H., L.J.L.), National Institute on Aging, Bethesda, MD; Icelandic Heart Association (S.S., G.E., O.K., T.A., V.G.), Kopavogur, Iceland; University Medical Center Utrecht (M.I.G.), Julius Center for Health Sciences and Primary Care, Utrecht, the Netherlands; Université Paris Descartes (J.-S.V.), Sorbonne Paris Cité, Paris, France; Faculty of Medicine (T.A., V.G.), University of Iceland, Reykjavik, Iceland; and Department of Radiology (M.A.v.B.), Leiden University Medical Center, Leiden, the Netherlands.
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Vilmundur Gudnason
From the Department of Preventive Medicine and Biometrics (L.S.G., A.I.S.), Uniformed Services University of the Health Sciences; Laboratory of Epidemiology, Demography and Biometry (L.S.G., A.I.S., M.I.G., J.-S.V., M.I.G., T.B.H., L.J.L.), National Institute on Aging, Bethesda, MD; Icelandic Heart Association (S.S., G.E., O.K., T.A., V.G.), Kopavogur, Iceland; University Medical Center Utrecht (M.I.G.), Julius Center for Health Sciences and Primary Care, Utrecht, the Netherlands; Université Paris Descartes (J.-S.V.), Sorbonne Paris Cité, Paris, France; Faculty of Medicine (T.A., V.G.), University of Iceland, Reykjavik, Iceland; and Department of Radiology (M.A.v.B.), Leiden University Medical Center, Leiden, the Netherlands.
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Lenore J. Launer
From the Department of Preventive Medicine and Biometrics (L.S.G., A.I.S.), Uniformed Services University of the Health Sciences; Laboratory of Epidemiology, Demography and Biometry (L.S.G., A.I.S., M.I.G., J.-S.V., M.I.G., T.B.H., L.J.L.), National Institute on Aging, Bethesda, MD; Icelandic Heart Association (S.S., G.E., O.K., T.A., V.G.), Kopavogur, Iceland; University Medical Center Utrecht (M.I.G.), Julius Center for Health Sciences and Primary Care, Utrecht, the Netherlands; Université Paris Descartes (J.-S.V.), Sorbonne Paris Cité, Paris, France; Faculty of Medicine (T.A., V.G.), University of Iceland, Reykjavik, Iceland; and Department of Radiology (M.A.v.B.), Leiden University Medical Center, Leiden, the Netherlands.
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Citation
Migraine, depression, and brain volume
The AGES-Reykjavik Study
Larus S. Gudmundsson, Ann I. Scher, Sigurdur Sigurdsson, Mirjam I. Geerlings, Jean-Sebastien Vidal, Gudny Eiriksdottir, Melissa I. Garcia, Tamara B. Harris, Olafur Kjartansson, Thor Aspelund, Mark A. van Buchem, Vilmundur Gudnason, Lenore J. Launer
Neurology Jun 2013, 80 (23) 2138-2144; DOI: 10.1212/WNL.0b013e318295d69e

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Abstract

Objective: To examine the joint association of migraine headache and major depressive disorder on brain volume in older persons without dementia.

Methods: Participants (n = 4,296, 58% women) from the population-based Age, Gene/Environment Susceptibility–Reykjavik Study were assessed for migraine headache in 1967–1991 (age 51 years [range 33–65]) according to modified International Classification of Headache Disorders–II criteria. In 2002–2006 (age 76 years [range 66–96]), lifetime history of major depressive disorder (depression) was diagnosed according to DSM-IV criteria, and full-brain MRI was acquired, which was computer postprocessed into total brain volume (TBV) (gray matter [GM], white matter [WM], white matter hyperintensities) and CSF volume for each study subject. We compared brain tissue volumes by headache categories with or without depression using linear regression, adjusting for intracranial volume and other factors.

Results: Compared with the reference group (no headache, no depression) TBV and WM and GM volumes were smaller in those with both migraine and depression (TBV −19.2 mL, 95% confidence interval [CI] −35.3, −3.1, p = 0.02; WM −12.8 mL, CI −21.3, −4.3, p = 0.003; GM −13.0 mL, CI −26.0, 0.1, p = 0.05) but not for those with migraine alone (TBV 0.4 mL, WM 0.2 mL, GM 0.6 mL) or depression alone (TBV −3.9 mL, WM −0.9 mL, GM −2.9 mL).

Conclusions: Reporting both migraine and major depressive disorder was associated with smaller brain tissue volumes than having one or neither of these conditions. Migraineurs with depression may represent a distinct clinical phenotype with different long-term sequelae. Nonetheless, the number of subjects in the current study is relatively small and these findings need to be confirmed in future studies.

GLOSSARY

AGES-Reykjavik=
Age, Gene/Environment Susceptibility–Reykjavik Study;
CI=
confidence interval;
DSM-IV=
Diagnostic and Statistical Manual of Mental Disorders, 4th edition;
GDS=
Geriatric Depression Scale;
ICHD-I and II=
International Classification of Headache Disorders, version I and II;
ICV=
intracranial volume;
MA=
migraine with aura;
MINI=
Mini-International Neuropsychiatric Interview;
MO=
migraine without aura;
NMH=
nonmigraine headache;
TBV=
total brain volume;
WMH=
white matter hyperintensities

Footnotes

  • Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Supplemental data at www.neurology.org

  • Received August 27, 2012.
  • Accepted in final form March 4, 2013.
  • © 2013 American Academy of Neurology
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