Migraine With Depression Linked to Reduced Brain Size

May 28, 2013

Older people with a history of migraines and depression may have smaller brain volumes than people with only 1 or neither of the conditions, according to a new study.

Lead author Larus S. Gudmundsson, PhD, National Institute on Aging, Bethesda, Maryland, commented to Medscape Medical News: "When compared with controls, patients who had had both migraine and depression were found to have a reduction in brain size of about 2%. That is equivalent to four and a half years of brain aging."

Dr. Gudmundsson said he did not know what the clinical relevance of their findings were, although reduced brain volume may indicate a decline in cognition. "I cannot say if this reduction in brain size would result in cognitive impairment, but a reduction in brain size is not something we want to happen. Our results give us some clue that migraine and depression may have a physical effect on the brain."

"Our study suggests that people with both migraine and depression may represent a unique group from those with only one of these conditions and may also require different strategies for long-term treatment," he added.

The results were published May 22 in Neurology.

Brain Tissue Volume

For the study, 4296 individuals who participated in the population-based Age, Gene/Environment Susceptibility–Reykjavik Study were assessed for migraine headache in 1967–1991, when they were between the ages of 33 and 65 years. In 2002–2006, when they were aged 66 to 96, they were assessed again and asked about a lifetime history of depression, as well undergoing full-brain MRI.

Brain tissue volume was calculated by headache categories with or without depression by using linear regression, adjusting for intracranial volume and other factors.

Results showed that compared with patients who had neither condition, those who had had both migraine and depression had reductions in total brain, white matter, and gray matter volumes.

Table. Reductions in Brain Volumes in Patients With a History of Migraine and Depression

Measure Volume Difference vs Reference Group (mL) P Value
Total brain volume –19.2 .02
White matter –12.8 .003
Gray matter –13.0 .05
White matter hyperintensities 3.0 .22


Results adjusted for sex, midlife age, years of follow-up, birth year, intracranial volume, midlife height, education, blood pressure, and antihypertensive medication.

Although the increase in white matter hyperintensities was not significant in the overall population with both migraine and depression, it was significant for women with a history of both these conditions.

"Migraineurs with depression may represent a distinct clinical phenotype with different long-term sequelae," the authors conclude. But they add that the number of patients in the current study is relatively small and that these findings need to be confirmed.

The reduction in brain volume was seen only in patients who had had both conditions, with no differences from the reference group found in those who had migraine or depression alone.

"Our results could suggest that the combination of depression and migraine in some way accelerates the aging process," Dr. Gudmundsson said. He suggested that this may be mediated through a pain or inflammation mechanism, noting that other studies have shown a link between pain and reduced brain size; in patients who have had hip and knee pain, this effect has been seen after hip/knee replacement. "Our results should, however, give more incentive to treat both migraine and depression better," he added.

But he cautioned that an alternative explanation could be that reduced brain size might be due to genetic differences or socioeconomic differences in early life that also contribute to migraine and depression.

Dr. Gudmundsson called for further studies in patients who have both of these conditions to investigate what these changes may mean. "Ideally, live course studies should be conducted where brain volume is measured at different times during life, with circumference of the head, weight and length at birth all added in," he said. "We need to examine at what age participants develop both migraine and depression and measure their brain volume changes over time in order to determine what comes first," he added.

The study was supported by the National Institutes of Health, the National Institute on Aging, the Icelandic Heart Association, and the Icelandic Parliament. Author disclosures are available with the original article.

Neurology. 2013;80:2138-2144. Abstract


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