Contingent negative variation in subjects at risk for migraine without aura

Migraine is a complex disease with a significant genetic background. One possible strategy to investigate the genetics of migraine is the evaluation of functional vulnerability markers or biological elementary endophenotypes in individuals with the greatest probability of developing the disorder (high-risk design). In this study the contingent negative variation (CNV) was recorded in 35 high-risk subjects with a positive family history of migraine without aura (FHP), 35 low-risk individuals without a positive family history (FHN), and 35 migraineurs (migraine without aura). FHP subjects and migraine patients differed significantly from FHN individuals with regard to amplitude and habituation slope of the early CNV component (initial CNV or iCNV). FHP participants demonstrated the same iCNV abnormalities and distribution among iCNV characteristics as migraineurs. The amplitude of the iCNV correlated significantly with the relative number of subjects suffering from migraine among first- and second-degree relatives. The higher the density of affected individuals in the family, the more pronounced were the CNV abnormalities in relatives. This study provides evidence that the familial factor contributes to the abnormal amplitude, and to a lesser degree, habituation of the iCNV, and that the iCNV may be used as a functional-genetic vulnerability marker in further research of migraine genetics.