Genetics of migraine headaches

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Migraines are often hereditary. It is estimated that 60% of migraine cases are caused by genetics. [1] The role of natural selection in the development of migraines is not known. Fitness-impairing disorders, including migraines, tend to disappear as a result of natural selection, and their frequency decreases to near the rate of spontaneous mutation.[ unreliable medical source? ] [2] However, it is estimated that migraines affect 15-20% of the population and is increasing. [1] This could suggest that a central nervous system (CNS) susceptible to severe, intermittent headache has been linked to an important survival or reproductive advantage. Five possible evolutionary explanations exist: i) migraine as a defence mechanism, ii) migraine as a result of conflicts with other organisms, iii) migraine as a result of novel environmental factors, iv) migraine as a compromise between genetic harms and benefits, and v) headache as a design constraint. [3] These considerations allow the treatment and prevention of migraine to be approached from an evolutionary medicine perspective.[ medical citation needed ]

Contents

Heritability

Studies of twins indicate a 34% to 51% genetic influence on the likelihood to develop migraine headaches. [4] This genetic relationship is stronger for migraines with aura than for migraines without aura.[ medical citation needed ] [5] A number of specific variants of genes increase the risk by a small to moderate amount. [6]

Single gene disorders that result in migraines are rare. [6] One of these is known as familial hemiplegic migraine, a type of migraine with aura, which is inherited in an autosomal dominant fashion. [7] [8] Four genes have been shown to be involved in familial hemiplegic migraine. [9] Three of these genes are involved in ion transport. [9] The fourth is an axonal protein associated with the exocytosis complex. [9] Another genetic disorder associated with migraine is CADASIL syndrome or cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. [10]

Evolution

Defence mechanism

The tendency to develop head pain when faced with a stressor or strong sensory stimuli can be explained in two ways. First, it may be a side effect of other CNS processes that provide important evolutionary advantages. One example is counteracting the dilation of cranial arteries to counteract dangerous vasoconstriction in the brain.[ unreliable medical source? ] [11] Second, migraine may be an example of how pain has evolved to encourage organisms to avoid potentially harmful situations. Olfactory-induced migraines (migraines stimulated by strong smells) have been explained as an attempt to interrupt the entry of toxins into the brain via the olfactory nerve.[ unreliable medical source? ] [12] Similarly, the low threshold for nausea and vomiting may be a mechanism to enhance the elimination of ingested toxins in food. Migraineurs have a lower prevalence of malignant neoplasms in the brain than controls, suggesting that migraines are protective against tumours. However, the mechanism responsible for this difference is unknown.[ unreliable medical source? ] [13]

Conflicts with other organisms

A headache-prone CNS may have resulted from interactions with other organisms in two ways. The first possibility is that migraine offers an advantage to the organism in fighting infection by increasing blood flow to the brain. [3] The second possibility is that certain pathogens evolved to cause headaches as a way of speeding their transmission to other organisms. [3] Finally, migraine may benefit neither the host nor the pathogen, but may simply be the result of certain infections. [14] This last explanation is concordant with the apparent negative impact of migraine on human fitness.[ original research? ]

Novel environmental factors

Modern environmental factors, with an increased sensory overload, may be especially permissive of the expression of genes that predispose to the disorder. If so, natural selection may not have had a chance to eliminate these genes yet. The increasing prevalence of migraine is easily a result of increased known triggers, such as bright light, loud noise, altered sleep/wake patterns, and emotional stress. This is an example of mismatch theory, which states that the current environment differs from the evolutionary environment of a particular trait. [3]

Genetic harms and benefits

Migraine is influenced on a polygenetic level (controlled by multiple genes). Therefore, researchers have theorized that migraine is a trade-off and that it exists as a spectrum of susceptibility, with the majority of the population falling in the "heterozygous" zone between the two extremes of experiencing no headache and experiencing frequent, incapacitating headache. While it is not known for certain how or whether mild forms of the disorder would enhance survival, there is evidence of enhanced visual sensitivity in family members of migraineurs.[ unreliable medical source? ] [15] Additionally, this compromise theory may explain the higher prevalence among women, especially pregnant women and women of reproductive age (25-40). The avoidance of threatening environments is historically more important to the reproductive success of women.[ unreliable medical source? ] [16] The compromise between genetic harms and benefits is commonly seen in other disorders, such as cystic fibrosis and sickle cell anemia.

Headache as a design construct

Finally, migraine may be a component of imperfect central nervous system design. Evidence has suggested a dysfunction of pain-inhibitory pathways in migraine and discordant interaction between the ancient brain stem design and the more evolved neocortex.[ unreliable medical source? ] [17] The brain stem may be unable to suppress excessive input from higher brain centres.

Related Research Articles

<span class="mw-page-title-main">Migraine</span> Disorder resulting in recurrent moderate-severe headaches

Migraine is a genetically influenced complex neurological disorder characterized by episodes of moderate-to-severe headache, most often unilateral and generally associated with nausea and light and sound sensitivity. Other characterizing symptoms may include nausea, vomiting, cognitive dysfunction, allodynia, and dizziness. Exacerbation of headache symptoms during physical activity is another distinguishing feature. Up to one-third of migraine sufferers experience aura: a premonitory period of sensory disturbance widely accepted to be caused by cortical spreading depression at the onset of a migraine attack. Although primarily considered to be a headache disorder, migraine is highly heterogenous neurological disease in its clinical presentation and is better thought of as a spectrum disease rather than a distinct clinical entity. Disease burden can range from episodic discrete attacks to chronic disease.

<span class="mw-page-title-main">Headache</span> Pain in the head or neck

Headache, also known as cephalalgia, is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of depression in those with severe headaches.

<span class="mw-page-title-main">Cluster headache</span> Neurological disorder

Cluster headache (CH) is a neurological disorder characterized by recurrent severe headaches on one side of the head, typically around the eye(s). There is often accompanying eye watering, nasal congestion, or swelling around the eye on the affected side. These symptoms typically last 15 minutes to 3 hours. Attacks often occur in clusters which typically last for weeks or months and occasionally more than a year.

A medication overuse headache (MOH), also known as a rebound headache, usually occurs when painkillers are taken frequently to relieve headaches. These cases are often referred to as painkiller headaches. Rebound headaches frequently occur daily, can be very painful and are a common cause of chronic daily headache. They typically occur in patients with an underlying headache disorder such as migraine or tension-type headache that "transforms" over time from an episodic condition to chronic daily headache due to excessive intake of acute headache relief medications. MOH is a serious, disabling and well-characterized disorder, which represents a worldwide problem and is now considered the third-most prevalent type of headache. The proportion of patients in the population with Chronic Daily Headache (CDH) who overuse acute medications ranges from 18% to 33%. The prevalence of medication overuse headache (MOH) varies depending on the population studied and diagnostic criteria used. However, it is estimated that MOH affects approximately 1-2% of the general population, but its relative frequency is much higher in secondary and tertiary care.

A headache is often present in patients with epilepsy. If the headache occurs in the vicinity of a seizure, it is defined as peri-ictal headache, which can occur either before (pre-ictal) or after (post-ictal) the seizure, to which the term ictal refers. An ictal headache itself may or may not be an epileptic manifestation. In the first case it is defined as ictal epileptic headache or simply epileptic headache. It is a real painful seizure, that can remain isolated or be followed by other manifestations of the seizure. On the other hand, the ictal non-epileptic headache is a headache that occurs during a seizure but it is not due to an epileptic mechanism. When the headache does not occur in the vicinity of a seizure it is defined as inter-ictal headache. In this case it is a disorder autonomous from epilepsy, that is a comorbidity.

<span class="mw-page-title-main">Cold-stimulus headache</span> Medical condition

A cold-stimulus headache, colloquially known as an ice-cream headache or brain freeze, is a form of brief pain or headache commonly associated with consumption of cold beverages or foods such as ice cream, popsicles, and snow cones. It is caused by a cold substance touching the roof of the mouth, and is believed to result from a nerve response causing rapid constriction and swelling of blood vessels, "referring" pain from the roof of the mouth to the head. The rate of intake for cold foods has been studied as a contributing factor. It can also occur during a sudden exposure of unprotected head to cold temperatures, such as by diving into cold water. A cold-stimulus headache is distinct from dentin hypersensitivity, a type of dental pain that can occur under similar circumstances.

<span class="mw-page-title-main">Calcitonin gene-related peptide</span> Peptide hormone in animals

Calcitonin gene-related peptide (CGRP) is a member of the calcitonin family of peptides consisting of calcitonin, amylin, adrenomedullin, adrenomedullin 2 (intermedin) and calcitonin‑receptor‑stimulating peptide. Calcitonin is mainly produced by thyroid C cells whilst CGRP is secreted and stored in the nervous system. This peptide, in humans, exists in two forms: CGRP alpha, and CGRP beta. α-CGRP is a 37-amino acid neuropeptide and is formed by alternative splicing of the calcitonin/CGRP gene located on chromosome 11. β-CGRP is less studied. In humans, β-CGRP differs from α-CGRP by three amino acids and is encoded in a separate, nearby gene. The CGRP family includes calcitonin (CT), adrenomedullin (AM), and amylin (AMY).

<span class="mw-page-title-main">Hemiplegic migraine</span> Medical condition

Hemiplegic migraine is a type of migraine headache characterized by motor weakness affecting only one side of the body, accompanied by aura. There is often an impairment in vision, speech, or sensation. It can run in the family, called familial hemiplegic migraine, or in a single individual, called sporadic hemiplegic migraine. The symptoms can be similar to a stroke, and may be precipitated by minor head trauma. People with FHM are advised to avoid activities that may trigger their attacks.

<span class="mw-page-title-main">Sporadic hemiplegic migraine</span> Medical condition

Sporadic hemiplegic migraine (SHM) is a form of hemiplegic migraine headache isolated cases of which are observed. It is a rare disease. It is considered to be a separate type of migraine.

Hemicrania continua (HC) is a persistent unilateral headache that responds to indomethacin. It is usually unremitting, but rare cases of remission have been documented. Hemicrania continua is considered a primary headache disorder, meaning that another condition does not cause it.

<span class="mw-page-title-main">LY-334370</span> Chemical compound

LY-334370 is a selective 5-HT1F receptor agonist which was under development by Eli Lilly and Company for the treatment of migraine headaches. The drug showed efficacy in a phase II clinical trial but further development was halted due to toxicity detected in animals.

<span class="mw-page-title-main">Orthostatic headache</span> Medical condition

Orthostatic headache is a medical condition in which a person develops a headache while vertical and the headache is relieved when horizontal. Previously it was often misdiagnosed as different primary headache disorders such as migraine or tension headaches. Increasing awareness of the symptom and its causes has prevented delayed or missed diagnosis.

New daily persistent headache (NDPH) is a primary headache syndrome which can mimic chronic migraine and chronic tension-type headache. The headache is daily and unremitting from very soon after onset, usually in a person who does not have a history of a primary headache disorder. The pain can be intermittent, but lasts more than 3 months. Headache onset is abrupt and people often remember the date, circumstance and, occasionally, the time of headache onset. One retrospective study stated that over 80% of patients could state the exact date their headache began.

Lupus headache is a proposed, specific headache disorder in patients with systemic lupus erythematosus (SLE). Research shows that headache is a symptom commonly described by SLE patients —57% in one meta-analysis, ranging in different studies from 33% to 78%; of which migraine 31.7% and tension-type headache 23.5%. The existence of a special lupus headache is contested, although few high-quality studies are available to form definitive conclusions.

Vestibular migraine (VM) is vertigo with migraine, either as a symptom of migraine or as a related neurological disorder.

The classification of all headaches, including migraines, is organized by the International Headache Society, and published in the International Classification of Headache Disorders (ICHD). The current version, the ICHD-3 beta, was published in 2013.

Migraine treatment may be either prophylactic (preventive) or abortive (rescue). Prevention is better than cure, so the ideal treatment goal is to prevent migraine attacks. Because migraine is an exceedingly complex condition, there are various preventive treatments which have their effect by disrupting different links in the chain of events that occur during a migraine attack. As rescue treatments also target and disrupt different processes occurring during migraine, these are summarized, with their relative merits and demerits.

The Migraine Specific Quality of Life (MSQoL) is a patient-reported outcome measure which assesses the quality of life of migraineurs. It is a 25-item questionnaire which is filled out by the patient and is used to determine how the patient's life has been affected by their migraines.

<span class="mw-page-title-main">Frank Clifford Rose</span> English neurologist

Frank Clifford Rose was a British neurologist, active in several journals and societies related to the specialty of neurology and its history, whose research contributed to the understanding of motor neurone disease, stroke and migraine. He developed an emergency stroke ambulance service with early neuroimaging, allowing for the detection of early reversible brain damage. In 1974, he established what would later be known as the Princess Margaret Migraine Clinic, a specialist clinic for headache at Charing Cross Hospital, where in 1965 he became their first appointed consultant neurologist.

<span class="mw-page-title-main">Recurrent painful ophthalmoplegic neuropathy</span> Medical condition

Recurrent painful ophthalmoplegic neuropathy (RPON), previously known as ophthalmoplegic migraine (OM), is a rare neurological disorder that is characterized by repeated headache attacks and reversible ipsilateral paresis of one or more ocular cranial nerves (CN). Oculomotor nerve (CNIII) is by far the most common cranial nerve involves in RPON, while abducens nerve (CNVI) and trochlear nerve (CNIV) involvements are also reported. Globally, RPON was estimated to have an annual incidence rate of 0.7 per million as of 1990, no further epidemiological studies have been conducted. It occurs more often in children and females.

References

  1. 1 2 Bron, Charlene; Sutherland, Heidi G.; Griffiths, Lyn R. (2021-04-22). "Exploring the Hereditary Nature of Migraine". Neuropsychiatric Disease and Treatment. 17: 1183–1194. doi:10.2147/NDT.S282562. PMC   8075356 . PMID   33911866.
  2. ↑ [ unreliable medical source? ]Nesse, RM; Williams, GC (November 1998). "Evolution and the origins of disease". Scientific American. 279 (5): 86–93. Bibcode:1998SciAm.279e..86N. doi:10.1038/scientificamerican1198-86. PMID   9796548. Erratum in Sci Am 1999 Mar;280(3):14.
  3. 1 2 3 4 Loder, E (1 October 2002). "What is the evolutionary advantage of migraine?". Cephalalgia (Review). 22 (8): 624–632. doi:10.1046/j.1468-2982.2002.00437.x. PMID   12383059. S2CID   1781214.
  4. ↑ Piane, M; Lulli, P; Farinelli, I; Simeoni, S; De Filippis, S; Patacchioli, FR; Martelletti, P (December 2007). "Genetics of migraine and pharmacogenomics: some considerations". The Journal of Headache and Pain (Review). 8 (6): 334–9. doi:10.1007/s10194-007-0427-2. PMC   2779399 . PMID   18058067.
  5. ↑ [ full citation needed ]The Headaches, Pg 232-233
  6. 1 2 Schürks, M (January 2012). "Genetics of migraine in the age of genome-wide association studies". The Journal of Headache and Pain (Review). 13 (1): 1–9. doi:10.1007/s10194-011-0399-0. PMC   3253157 . PMID   22072275.
  7. ↑ de Vries, B; Frants, RR; Ferrari, MD; van den Maagdenberg, AM (July 2009). "Molecular genetics of migraine". Human Genetics (Review). 126 (1): 115–32. doi:10.1007/s00439-009-0684-z. PMID   19455354. S2CID   20119237.
  8. ↑ Montagna, P (September 2008). "Migraine genetics". Expert Review of Neurotherapeutics (Review). 8 (9): 1321–30. doi:10.1586/14737175.8.9.1321. PMID   18759544. S2CID   207195127.
  9. 1 2 3 Ducros, A (Apr 22, 2013). "[Genetics of migraine]". Revue neurologique. 169 (5): 360–71. doi:10.1016/j.neurol.2012.11.010. PMID   23618705.
  10. ↑ Aminoff, Roger P. Simon, David A. Greenberg, Michael J. (2009). Clinical neurology (7 ed.). New York, N.Y: Lange Medical Books/McGraw-Hill. pp. 85–88. ISBN   9780071664332.
  11. ↑ [ unreliable medical source? ]Edvinsson, L.; Olesen, I. J.; Kingman, T.; McCulloch, J.; Uddman, R. (1 October 1995). "Modification of vasoconstrictor responses in cerebral blood vessels by lesioning of the trigeminal nerve: possible involvement of CGRP". Cephalalgia. 15 (5): 373–383. doi:10.1046/j.1468-2982.1995.1505373.x. PMID   8536296. S2CID   6338356.
  12. ↑ [ unreliable medical source? ]Covelli, Vito; Massari, Franco; Ďandrea, Lucia; Cervo, M. Augusta; Buscaino, Giuseppe Andrea; Jirillo, Emilio (1 January 1994). "Could migraine be a "protective factor" against tumors?". International Journal of Neuroscience. 75 (1–2): 139–143. doi:10.3109/00207459408986297. PMID   8050847.
  13. ↑ [ unreliable medical source? ]Snyder, RD; Drummond, PD (1 November 1997). "Olfaction in migraine". Cephalalgia (Clinical trial). 17 (7): 729–732. doi:10.1046/j.1468-2982.1997.1707729.x. PMID   9399001. S2CID   21617632.
  14. ↑ Cochran, Gregory M; Ewald, Paul W; Cochran, Kyle D (1 January 2000). "Infectious causation of disease: an evolutionary perspective". Perspectives in Biology and Medicine (Historical article). 43 (3): 406–448. CiteSeerX   10.1.1.182.5521 . doi:10.1353/pbm.2000.0016. PMID   10893730. S2CID   5908583.
  15. ↑ [ unreliable medical source? ]Puca, F.; de Tommaso, M.; Tota, T.; Sciruicchio, V. (1 June 1996). "Photic driving in migraine: correlations with clinical features". Cephalalgia. 16 (4): 246–250. doi:10.1046/j.1468-2982.1996.1604246.x. PMID   8792036. S2CID   23967616.
  16. ↑ [ unreliable medical source? ]Stewart, Walter F. (1 January 1992). "Prevalence of migraine headache in the United States. Relation to age, income, race, and other sociodemographic factors". JAMA: The Journal of the American Medical Association. 267 (1): 64–9. doi:10.1001/jama.1992.03480010072027. PMID   1727198.
  17. ↑ [ unreliable medical source? ]Weiller, C; May, A; Limmroth, V; Jüptner, M; Kaube, H; Schayck, RV; Coenen, HH; Diener, HC (July 1995). "Brain stem activation in spontaneous human migraine attacks". Nature Medicine. 1 (7): 658–60. doi:10.1038/nm0795-658. PMID   7585147. S2CID   20878130.
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