title: Elevated levels of GABA+ in migraine detected using (1) H-MRS.
abstract: γ-Aminobutyric acid (GABA) has been implicated in several pain conditions, yet no study has systematically evaluated GABA levels in migraine using (1) H-MRS. The accurate detection, separation and quantification of GABA in individuals with migraine could elucidate the role of this neurotransmitter in migraine pathophysiology. Such information may eventually be useful in the diagnosis and development of more effective treatments for migraine. The aims of this study were therefore to compare the concentration of GABA+ in individuals with migraine with that in asymptomatic individuals, and to determine the diagnostic potential of GABA+ in the classification of those with or without migraine. In this case-control study, GABA+ levels in the brain were determined in 19 participants with migraine and 19 matched controls by (1) H-MRS using Mescher-Garwood point-resolved spectroscopy (MEGA-PRESS) sequence. The diagnostic accuracy of GABA+ for the detection of migraine and the optimal cut-off value were determined by receiver operating characteristic analysis. GABA+ levels were significantly higher (p = 0.002) in those with migraine [median, 1.41 institutional units (IU); interquartile range, 1.31-1.50 IU] than in controls (median, 1.18 IU; interquartile range, 1.12-1.35 IU). The GABA+ concentration appears to have good accuracy for the classification of individuals with or without migraine [area under the curve (95% confidence interval), 0.837 (0.71-0.96); p < 0.001]. The optimal GABA+ cut-off value for migraine was 1.30 IU, with a sensitivity of 84.2%, specificity of 68.4% and positive likelihood ratio of +2.67. The outcomes of this study suggest altered GABA metabolism in migraine. These results add to the scarce evidence on the putative role of GABA in migraine and provide a basis to further explore the causal relationship between GABA+ and the pathophysiology of migraine. This study also demonstrates that GABA+ concentration has good diagnostic accuracy for migraine. These findings offer new research and practice directions for migraine diagnosis.
authors.affiliation: The University of Sydney Faculty of Health Sciences, Lidcombe, NSW, Australia.|University of the Philippines College of Allied Medical Professions, Manila, Philippines.
authors.forename: Maria-Eliza R
authors.initials: ME
authors.lastname: Aguila
authors.affiliation: Brain and Mind Research Institute, Sydney Medical School, Camperdown, NSW, Australia.
authors.forename: Jim
authors.initials: J
authors.lastname: Lagopoulos
authors.affiliation: The University of Sydney Faculty of Health Sciences, Lidcombe, NSW, Australia.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Leaver
authors.affiliation: The University of Sydney Faculty of Health Sciences, Lidcombe, NSW, Australia.
authors.forename: Trudy
authors.initials: T
authors.lastname: Rebbeck
authors.affiliation: The University of Sydney Faculty of Health Sciences, Lidcombe, NSW, Australia.|Neuroscience Research Australia and The University of New South Wales, Randwick, NSW, Australia.
authors.forename: Markus
authors.initials: M
authors.lastname: Hübscher
authors.affiliation: The University of Sydney Faculty of Health Sciences, Lidcombe, NSW, Australia.
authors.forename: Patrick C
authors.initials: PC
authors.lastname: Brennan
authors.affiliation: The University of Sydney Faculty of Health Sciences, Lidcombe, NSW, Australia.
authors.forename: Kathryn M
authors.initials: KM
authors.lastname: Refshauge
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008881:Migraine Disorders / Q000175:diagnosis* / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000378:metabolism; D066244:Proton Magnetic Resonance Spectroscopy / Q000379:methods*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014018:Tissue Distribution; D015854:Up-Regulation; D055815:Young Adult; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D018377:Neurotransmitter Agents; D005680:gamma-Aminobutyric Acid
keywords: GABA; MRS; ROC curve; migraine disorders; sensitivity; specificity