Bipolar disorder and migraines linked
A gene variant can be a risk factor for both medical problems, according to a new study.
The researchers think some of the same signal systems in the brain are involved in migraines as well as bipolar disorder.
A scientist at the University of Bergen recently found a gene variation that can partly explain why many suffer a combination of both of these health disorders.
Researchers designate the genetic variants that make a person vulnerable to a specific disease as susceptibility variants. Some of these can make a person susceptible to more than one disease.
Migraine headaches and bipolar disease, which used to be called manic depression, share certain common characteristics. One is the fluctuation of symptoms.
Migraine patients can be free of symptoms for long periods before suddenly suffering attacks. The moods of bipolar persons are likewise known to swing back and forth at various intervals.
“Among the over 1,300 bipolar patients included in the analysis, about a third also had migraines,” says physician and researcher Kaya Kvarme Jacobsen at the University of Bergen.
She used DNA samples of American patients in this study.
Found a common variant
It is recognised that persons with bipolar disorder have a three to four-time greater chance of suffering migraines than the rest of the population.
By comparing the genes of bipolar patients who also suffered migraines with ones who did not, the researcher found a common denominator in their genetic makeup.
Kvarme Jacobsen found a gene variant which looks to be a common susceptibility factor. Scientists think this gene can affect one of many signal systems that can contribute to both these diseases.
“This is a new building block in the laborious work in understanding the mechanisms behind both diseases,” says Jacobsen.
“We already know that patients who have migraines and bipolar disorder suffer much stronger symptoms of both disorders,” she says. Kvarme Jacobsen thinks these patients might be give relief from other medications than the ones used for persons with just one of these medical predicaments.
Migraines much more frequent
Bipolar disorder is much less common than migraines. Fortunately, most migraine patients are not also bipolar.
While perhaps a half million – nearly one in ten – Norwegians suffer migraines, only about one percent, or 50,000, are diagnosed with the most serious type of bipolar disorder, designated as type 1.
Some 150,000 Norwegians have some form of bipolar disorder, according to the Norwegian medical encyclopaedia Store medisinske leksikon.
One gene does not explain it all
Will it be possible one day to turn off these susceptibility genes through genetic therapy?
“Knocking out a gene will not do that much. But the discovery can make it possible to use genetic manipulation, for instance CRISPR/Cas9 among animals, to study which effects this can have on the neural system when we block specific genes,” she explains.
Chief Physician Ulrik Fredrik Malt at Division of Surgery and Clinical Neuroscience of the Oslo University Hospital puts it thusly:
“A gene explains very little of an association, even if it is statistically significant. In this study they found a link in the large sample but not in the smaller sample. This illustrates that the gene cannot really explain so much of the connection,” says Malt.
Malt goes on to say that this is rather typical of genetic studies of mental disorders. A single gene in this context will often only have a three or four percent impact.
Many genes involved
The study was part of Jacobsen’s doctoral dissertation at the University of Bergen. She has also analysed susceptibility genes for several other disorders, such as ADHD, depression and schizophrenia.
She found information supporting the idea that small changes in genetic material need to be present for developing one of these neuropsychiatric disorders. Not just in one gene, but in a large number of genes.
These genes regulate the brain’s development and signal functions.
Scientists need the DNA of persons with and without specific disorders to implement such controlled studies.
An analysis can then be made to see if variants of genes are more common in one group than the other.
“Differences in incidence can indicate that a gene variant can alter the risk of a disorder,” says Kvarme Jacobsen.
Nature or nurture
Earlier studies have shown that genetic risk factors comprise between 60 and 90 percent of the cause of neuropsychiatric disorders.
Researchers have found this out in part by comparing the incidence of diseases among regular twins and identical twins.
If both identical twins have a disease it could be caused by their genetic heritage as well as their shared environment. But if twins from two ova have the same disease, the environmental factor is the more likely culprit, as just half of their genetic material is identical.
“The rest of the risk factors will be from environmental factors,” explains the researcher.
The studies of bipolar disorder patients with and without migraines were made with data material collected in the form of DNA analyses from saliva or blood samples that American medical researchers shared in collaborative initiatives with researchers at the University of Bergen.
“All who donated DNA to the study have signed compliance for the studies to which they were recruited,” informs Kvarme Jacobsen.
Kaya Kvarme Jacobsen: Genetic susceptibility across neuropsychiatric disorders - genome-wide, candidate gene and interaction analyses. Doctoral dissertation, University of Bergen, December 2016.
Translated by: Glenn Ostling