People with a specific variation in a gene affecting circadian rhythms have more migraines under financial stress, according to a new study presented at the European College of Neuropsychopharmacology (ECNP) conference in Paris.
The CLOCK gene ( for Circadian Locomotor Output Cycles Kaput) affects both the persistence and period of circadian rhythms; as such, it plays a significant role in regulating many rhythmic patterns in the body, including levels of cortisol (a primary stress hormone) and body temperature.
Migraines have highly complex origins involving a large number of genes combined with environmental effects that act through multiple pathways in the central nervous system.
Previous research has shown that variations in circadian genes (which affect how the body controls and responds to environmental changes, such as changes in light) have an impact on mood disorders. In the new study, the researchers wanted to investigate whether these genes were also associated with migraine development.
For the study, researchers checked 999 patients from Budapest, Hungary, and 1,350 from Manchester, England, for two variants (single nucleotide polymorphisms, SNPs) of the CLOCK gene and investigated how these are associated with migraine.
No direct link was found between the gene and migraine, but when the researchers factored in stress (financial stress, measured by a financial questionnaire), those particular gene variants increased the odds of migraine by around 20 percent in participants who suffered from financial hardship.
“This is a really interesting study on the interaction of genetics with stress in migraine. The studied gene is involved in the circadian system, which has previously been shown to be implicated in mental disorders such as bipolar disorder, which intriguingly is comorbid with migraine,” said Professor Andreas Reif from University Hospital in Frankfurt, Germany.
“Thus, this study might provide a clue how these diseases might be linked on the genetic level which is interesting as such. But even beyond this, the study demonstrates how an environmental risk factor exerts its effect only in the presence of a given genetic risk factor. This has not been done to a great extent in migraine, making this study an exciting new lead.”
Specifically, the researchers studied functional single nucleotide polymorphisms within the CLOCK gene. These are able to influence how much protein is transcribed from the gene. Because this protein controls the body clock machinery, variants in this gene may impair processes that can prevent migraine in the face of stress.
“This work does not show what causes migraine — there is no single cause — but it does show that both stress and genetics have an effect,” said researcher Dr. Daniel Baksa from Semmelweis University in Budapest.
“In the work presented here, we were able to show that stress — represented by financial hardship — led to an increase in migraine in those who have a particular gene variant. What we need to do now is to see if other circadian gene variants in association with different stress factors cause the same effect.”
“The strength of our study is that we saw the same effect in two independent study groups, in Budapest and Manchester, so we think it is a real effect,” he said.
“The investigated gene variants are present in around one third of the population, so they are common variants with small effect size. Our results shed light on one specific mechanism that may contribute to migraine. What it does mean is that for many people, the stress caused by financial worries can physically affect you.”