The Headache Research Center (HRC) is justified by the major health, social and economic problem of the migraine disorder which affects 17.6% of women and 6% of males in the United States. The HRC will provide the opportunity for focused and longitudinal research studies of headache, the commonest human malady. The overall goal of this proposal is to investigate the cause, mechanisms, and consequences of migraine. The concept is proposed that migraine is primarily a brain response to transient shifts of physiology whether systemic or in the brain, which modify the threshold for an attack. The underlying hypothesis is that the threshold for migraine is the state of polarization of cellular membranes in certain brain regions or neuronal systems. Project 1 is a population-based epidemiological study to substantiate and expand upon preliminary observations that migraine is associated with psychiatric co-morbidity particularly major depressive disorder and anxiety disorder. Project 2 uses a clinic and population based epidemiological approach to substantiate and expand upon preliminary observations that the prevalence of antiphospholipid antibodies in migraine is increased. Project 3 uses 31/Phosphorous magnetic resonance spectroscopy to measure brain energy metabolism and magnesium based on the hypothesis that migraine is associated with a disorder of mitochondrial oxidative phosphorylation, possibly secondary to magnesium deficiency. Project 4 uses magnetoencephalography to explore the mechanisms of the migraine attack based on the hypothesis that the aura of migraine is initiated by neuronal depolarization followed by spread of a depolarizing wave and suppression of neuronal function. The center is supported by an Administrative and Recruitment Core. Novel strategies are applied in the recruitment of subjects from a population base for epidemiological and clinical investigational studies. A Biostatistics Core assists and consults in the management and analysis of scientific data.
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