Gene Mutations and Migraines

Many people experience headaches, but not as many people experience migraines. Migraines tend to cause intense pain in one side of the head, are often associated with nausea, dizziness, auras, light/noise/smell sensitivity, and they tend to last between 4 and 72 hours. For people who regularly experience migraines, it can be debilitating and make it very difficult to plan things as an attack can happen at any time, sometimes without warning. Some people have specific triggers for migraines and some people don't, but most cases of migraines appear to have a genetic component.

A lot of people who are diagnosed with migraines have at least one immediate family member who also experiences them, suggesting that there is a genetic component to a degree. Although some migraines are solely triggered by lifestyle (such as sudden change in diet or daily routine), researchers have found many different gene mutations that could be responsible for migraines. Unfortunately, because there are many different genes and they don't all affect the same pathways in the brain, there isn't one targeted therapy that could wipe out migraines for everyone.

The most interesting thing about the genetic component of migraines is that there has only been one gene (TRPM8) linked directly to a pain pathway. Considering the fact that migraines are so painful, most people would assume that the related genes would directly affect the pain pathway, but in fact most of the mutations cause changes in neurotransmitter concentrations. Instead of the concentrations causing more nerves to fire, they end up in the bloodstream in the brain, and the increased concentration can actually cause the blood vessels to become inflamed. The inflammation is what causes the intense pain sensation in the brain.

I suffer from migraines myself, so to see so many factors playing a role in migraines it makes it hard to believe that there will ever be a cure. Neurologists typically default to checking for lifestyle changes or imbalances of different chemicals that relate to your diet. But for people like me who can't seem to find a trigger for their migraines, it makes me wonder if my genetics are the sole cause for them. If that is the case, I think it will be very hard to find the right treatments for people like me since it is nearly impossible to sense when a migraine is coming on, and most migraine medications on the market nowadays are only effective if you take them the minute you feel the migraine beginning. More research is desperately needed in this subject because if a common pathway is found somewhere, there may be a common treatment that can be used for everyone that regularly experience migraines. At the very least, more research will allow us to further understand the mechanisms behind migraines and perhaps will clear up many of the gray areas that still remain in this condition.

Links for the articles:

Genetics of migraine in the age of genome-wide association studies:
https://thejournalofheadacheandpain.biomedcentral.com/track/pdf/10.1007/s10194-011-0399-0

Molecular genetics of migraine:
https://link.springer.com/content/pdf/10.1007/s00439-009-0684-z.pdf

Mutation Causes Protein Dysfunction Induces Migraines

Migraines are a type of recurring headache that occurs on one part of the head. There are several types of migraines ranging in severity and can cause symptoms from nausea and weakness to temporary memory loss and speech/motor function, last from an hour to weeks at a time, and cause an increased risk of strokes. Migraines are often hereditary and 15% of adults who suffer do not respond to treatments available.

Researchers at CNRS discovered a mutation that causes dysfunction in a protein which induces migraines. Migraines are related to hyperexcitability in sensory neurons. The researchers found that a mutation in the coding causes a split in the protein with one being inactive and the other targets ion channels at K2P2.1 (a protein in the potasisum channel) which stimulates neural electrical activity causing migraines.

The above picture is from a study performed on mice at the Institut de Biologie Valrose in France. The diagram shows the normal pathway and the mutated pathway of the TRESK gene. In the mice with the TRESK mutation, they exhibit TRESK-MT1 and TRESK-MT2 which in turns cause hyperexcitability instead of the normal TRESK and normal excitability.

I found this discovery very interesting because I am among the 15% of the population that does not respond to migraine medications and treatments. Medications for chronic migraines are typically anti-depressive or anti-epileptic, usually beta-blockers, calcium channel blocker, or serotonin blockers, which both can worsen migraines and cause unwanted side effects. The discovery that a mutation in the potassium channel is related to migraines allows for a further understanding of migraines and can lead to a more effective drug to be developed.

Genetic Foundation of Migraines

On May 3rd, a study in the journal Neuron was published on research of why some families are more susceptible to getting migraines and how genetics could influence which type of migraine someone would get. There is two possible ways that migraines were thought to be inherited which is through linkage or polygenic inheritance. Linkage, or the passing down of chromosomes from parent to child, have three genes associated, CACNA1A, ATP1A2, and SCN1A.

The scientists believed that these types of genes control the severe migraines that show stroke like symptoms and fall under the Mendelian model for inheritance. For polygenic inheritance, it carries the idea that a group of genes collectively contribute that characteristic even if each gene only contributes a tiny amount. 

For the research, the scientists created a polygenic risk score which estimated the genetic burden of common variants. They gathered data from a previous genome association wide study. Hundreds and thousands of loci that were linked to migraines were incorporated. Researchers then tested the influence of the risk score and the three mendelian linked genes with a large family of migraine sufferers in Finland. They used genetic data of 1589 families compared them to a control family.  The researchers found out that time and time again results proved that the polygenic common variants were driving migraine risk way more than the mendelian traits. The end result was that it was more likely the person with the migraine has a greater genetic burden of common polygenic variants to blame. 

I believe this research is a good start with good findings to a problem that 15-20% of adults go through. If we can continue to build on research and find out what biological pathways the genes affect than we can find a better solution to a problem that almost a quarter of adults face on a daily basis. 

Genes Found are Related to Migraines

    Previously believed to be caused purely by stress, emotions, and depression, migraines are now believed to have over 40 genes that can trigger the onset of a debilitating migraine, sometimes also being accompanied by nausea, blind spots, flu-like symptoms, disorientation, and trouble thinking.  Specifically, calcitonin, which is a gene-related peptide abundantly found in people who tend to receive migraines more often than others, is being studied and tested to find a cure.  This peptide produces the swelling of blood vessels within the brain, ultimately resulting in a migraine to form. In fact, about 50% of the people who develop severe migraines is due to their genetic predisposition.

    While there are genes that enable migraines to form, they can also be triggered by by external factors, possibly smells, alcohol, specific foods, lights, and especially noises, that takes a normal headache to the next level.  When this occurs, it could last anywhere from 4 hours to four days.  It is when these outside factors become so extremely amplified within the brain and activates the neural networks, causing a very painful migraine. 

    As technology improves and scientists are able to better distinguish which specific genes are directly linked to the development of severe migraines, new forms of medication could possibly be made.  I think it will be able to provide an entirely new lifestyle change to people afflicted and look forward to cures being fabricated, especially as someone who oftentimes get migraines.

Are Migraines Genetic?

 
   

    A recent study was conducted to see whether or not certain migraine types are genetically passed down.  A lot of the time members of the same family all get the same migraines.  Previous research discovered that CACNA1A, ATP1A2, and SCN1A are genes that associated with a migraine and are inherited.  Another way they have been discovered to be inherited is that a migraine is polygenic. For this study they wanted to test what of the two or if both caused the migraines.
   
    In this study they discovered that the polygenic way was the answer. This means that more than one set of genes of causes the migraines in all the individuals in a family. This discovery can help to further develop drugs to help sufferers get treated for their migraine symptoms.

  https://www.sciencedaily.com/releases/2018/05/180503142926.htm

Women's Emotions Do Not Cause Their Migraines

A very common misconception is that women's migraines are directly related to their stress and emotions and their inability to manage them. It was also thought that the likelihood of a women getting a migraine would increase when it was her "time of the month" only because that is when women tend to be more emotional. In reality, neurologists have discovered that this abnormal brain activity actually has nothing to do with emotions.

36 million people suffer from migraines in the United States and women are three to four times more likely to experience them. Women's migraines do correlate with their menstrual cycle, though not because of a change in emotions. Hormone fluctuation, along with environmental factors attribute to migraines. Those are not the only factors though. It has been found that variations of more than 40 genes are associated with migraines and there is a genetic component to at least 50% of migraine cases. This genetic predisposition to migraines, along with certain "triggers" (such as light sensitivity) activate networks in the brain that are interconnected and allow for a migraine to occur.

Suffering from migraines myself, this has been an interesting read and has broadened my understanding of why I experience migraines. I have always focused on finding specific triggers to my migraines. I have now learned that even though certain things may seem to increase my likelihood of a migraine, they are not the only piece of the puzzle, and that I am most likely genetically predisposed to experiencing migraines.

http://akhelp.com/907chiro/wp-content/uploads/2014/05/migraine-and-blurred-vision.jpghttp://www.nytimes.com/2016/04/07/health/debunking-migraine-misconceptions.html

Gene Found to Help Combat Strokes

Researchers from University of London, along with researchers from the United States and Europe, found a gene known as PHACTR1.  This gene has been found to reduce cervical artery dissection, which is a tear in an artery that leads to the brain.  Cervical artery dissection is one of the leading causes of strokes in young and middle-aged adults.  This disease can also lead to compression of adjacent nerves and to blood clotting, hence the strokes.  Individuals with the PHACTR1 gene have reduced risk from not only cervical artery dissection, but from migraines and heart attacks.

One of the researchers, Professor Pankaj Sharma, believes the discovery of this gene is a very important breakthrough.  Not just due to finding this gene, but because the study of this particular area of the genome provides a better understanding of how it affects the vascular system.  This discovery can lead to new treatments for strokes, in addition to cervical artery dissection.  The study of the genome around PHACTR1 could lead to more knowledge and new treatments of other vascular, heart, and brain diseases.

I find it extremely fascinating how many discoveries are being made in such a short amount of time.  The scientist are constantly finding new genes or linking old genes to different diseases.  I think if we keep studying the genome we will be able to handle old disease and new diseases as they pop up.  If not, we will at the very least have a good understanding of the disease and how to go about dealing with it.  Genome studying can only be good.

Article:  http://www.medicalnewstoday.com/releases/286004.php 

Related Article:  http://www.independent.co.uk/life-style/health-and-families/health-news/scientists-discover-stroke-protection-gene--that-also-guards-against-heart-attack-and-migraine-9880349.html

Gene Linked to Reduced Stroke Risk

Researchers recently discovered a gene that helps prevent one of the major causes of stroke. This discovery could possible lead to new treatments for young and middle aged adults. Researchers from the University of London and an international team have discovered a variant of the PHACTR1. Individuals with this variant are known to have a reduced risk of cervical artery dissection caused by a tear in an artery leading to the brain.

This discovery will lead to new treatment and prevention options for adults with diseases that increase the risk of strokes. This same variant may also be linked to a reduced risk for migraines and heart attacks. These findings have help scientists have a greater understanding of how genomes related to the vascular systems. This means this discovery could also help with treatment and prevention for many disabling vascular conditions. More research will be conducted to identify these specific genes and genomes in hopes to find the causes of strokes and heart disease. This would be an incredible medical breakthrough and hopefully save many lives in the future.

Original Article: http://www.medicalnewstoday.com/releases/286004.php

Related Article: http://www.bbc.com/news/health-28117422

Study Suggests Migraines are Linked to Defective 'Insulation" Around Nerve Fibers

Bahman Guyuron, an ASPS member surgeon at Case Western Reserve University in Cleveland found that there are abnormalities with the myelin sheath in patients that have migraines. Myelin sheath is a fatty material that protects and insulates the neurons.

The research consisted of 15 patients that underwent surgery for migraines and 15 patients that were undergoing a cosmetic forehead lift. They found in the results that the myelin sheath was either missing or damaged in the 15 patients that underwent surgery for migraines compared to the 15 patients that got a cosmetic forehead lift. Dr. Guyuron states that damage to the myelin sheath can make the nerves more  prone to irritation which can trigger migraines.

Dr.Guyuron noticed that many migraine patients had reduced symptoms after undergoing a cosmetic forehead lift. This surgery involved the removal of some muscle and vessel tissue that surrounded the cranial nerves. Since this shows that cranial nerves are also involved this could lead to other opportunities to treat patients in an easier way.

I really enjoyed reading this article because I live with migraines and seeing that they are starting to find different procedures to treat them is great. The more research they do the more they find out and this could possibly lead to more opportunities to find out different ways to treat migraines. It could lead to more easier and inexpensive ways which could be helpful for everyone.

Article: http://www.sciencedaily.com/releases/2014/11/141103113557.htm

Stress causing headaches

On February 20, 2014, Honor Whiteman wrote an article called “High stress levels increase frequency of headaches.” This article, published on Medical News Today, explains the study of how stress and headaches are related. Research shows high stress levels is linked to increased occurrence of headaches. Dr. Sara H. Schramm of University Hospital at the University Duisburg-Essen in Germany, and her research team analyzed 5,159 people between the ages of 21 and 71 years old. The researchers looked at tension-type headache, migraine, and non-classified headaches.  After the researchers analyzed their data they found that for each headache type, the more stress a person experienced, the more headaches they had each month. Dr. Schramm says that the study results show that stress is a common cause of headaches, and patients who suffer frequent headaches should adopt stress management strategies with help from their doctor.

The article was very detailed. I do agree with the study findings. I believe that stress levels increase the occurrence of headaches. Everyone goes through stress but everyone goes through different amounts. Stress can affect us mentally and physically. Stress can lead to other problems like depression. Everyone experiencing headaches should adopt stress management strategies to reduce the amount of stress and headaches. This will result in the reduction of future health issues. 

Migraine may permanently change brain structure

Migraines have been considered a benign disorder without long-term consequences until a recent study proved otherwise.  Migraines can permanently alter the brain structure in multiple ways such as increasing the risk of brain lesions, white matter abnormalities and altered brain volume compared to people without the disorder, even stronger in those that have migraine with aura.  A meta-analysis study consisted of 6 population based studies and 13 clinic-based studies to test if migraine with aura had increased risk of silent abnormalities, brain lesions or brain volume changes on MRI brain scans.  Results showed migraine with aura increased risk of white matter brain lesions by 68% and migraine with no aura 34% increase to those that don’t suffer from migraines.  Migraines affect about 10-15% of the general population.  Hopefully through more study research can clarify the association of brain structure changes to attack frequency and length of the disease.

 

http://www.sciencedaily.com/releases/2013/08/130828172644.htm
https://www.aan.com/PressRoom/Home/PressRelease/1204

Mutation Related to Migraines Identified Through Sleep Patterns

 According to Medical News Today, a link has been identified between migraines and an advanced and unusual sleep disorder.  The disorder is known as familial advanced phase sleep syndrome.  FAPSS is a rare sleep disorder in which an individual's circadian rhythm causes that person to go to sleep at an early time and then wake up well before dawn.  For example, someone with this disorder would be known to go to bed around 6:00 pm and then would wake up around 3:00 am.  Because this sleep disorder is so rare, doctors were able to determine a connection when they noticed that those individuals that are affected by the disorder are also commonly affected by migraines.

  So, what's the link?  The mutation occurs when the enzyme CKIδ becomes impaired.  The enzyme CKIδ is known as a common "housekeeping" enzyme because it functions in maintaining several different, basic processes and regulations throughout the body.  One of CKIδ's functions is to help control the circadian rhythm that determine's the sleep cycle. 

In the mid 1990s, Dr. Robert E. Shapiro was working with a family that was known to have familial advanced phase sleep syndrome.  It was by working with this family that he was able to make the connection that the family members also suffered from migraines.  Because migraines alone are so vague and common, the mutation in the CKIδ enzyme would have been impossible to discover based on the presence of migraine symptoms alone.  Eventually, the mutation was identified to be the cause of the sleep disorder and further studies were then conducted to decipher whether or not the mutation also had a direct impact on migraines. 

The mutation in the CKIδ gene now creates a total of 6 genes that have been isolated and found to cause migraines.  Studies are currently underway to develop a new drug therapy for the treatment of migraines.