The primary headaches: genetics, epigenetics and a behavioural genetic model

Abstract

The primary headaches, migraine with (MA) and without aura (MO) and cluster headache, all carry a substantial genetic liability. Familial hemiplegic migraine (FHM), an autosomal dominant mendelian disorder classified as a subtype of MA, is due to mutations in genes encoding neural channel subunits. MA/MO are considered multifactorial genetic disorders, and FHM has been proposed as a model for migraine aetiology. However, a review of the genetic studies suggests that the FHM genes are not involved in the typical migraines and that FHM should be considered as a syndromic migraine rather than a subtype of MA. Adopting the concept of syndromic migraine could be useful in understanding migraine pathogenesis. We hypothesise that epigenetic mechanisms play an important role in headache pathogenesis. A behavioural model is proposed, whereby the primary headaches are construed as behaviours, not symptoms, evolutionarily conserved for their adaptive value and engendered out of a genetic repertoire by a network of pattern generators present in the brain and signalling homeostatic imbalance. This behavioural model could be incorporated into migraine genetic research.

Molecular genetics of migraine

“…These modiWcations decrease (or increase) gene expression and thus inXuence molecular pathways (Jirtle and Skinner 2007). Epigenetic eVects occur in early development but may change over lifetime, by lifestyle and diet, and it has been suggested that changes for instance in development of the individual or triggers such has stress determine the 'epigenetic outcome' and thus may aVect migraine susceptibility (Montagna 2008). It would be interesting to subgroup migraine patients for genetic and/or epigenetic studies according to their self-reported triggers.…”

Antifolates and MTHFR

“…9 Although there are numerous studies reporting that homocysteine is associated with migraine headaches, for example, [10][11][12] there is only 1 study describing the interference of MTHFR with ocular accommodation. 13 FIGURE 1.…”

State of Immune System in Patients With Primary Headaches

“…Однако вы-явление цитокинового дисбаланса у больных ПГБ, не имеющих клинических признаков им-мунных расстройств, позволяет предположить, что у ряда пациентов имеется доклиническая ста-дия иммунопатологии, либо цитокины выступа-ют в качестве самостоятельных патогенетических факторов цефалгий. Как причина цитокинового дисбаланса рассматриваются генетические осо-бенности [23], лекарственный абузус [22], стресс и депрессия [19].…”