Those of us who live free of the chronic pain caused by endometriosis can only imagine what a life of constant discomfort is like. Depression can feel like an inevitable consequence, risking assumptions that distract us from searching for further causes.
Now, research led by geneticists from the Queensland University of Technology in Australia has uncovered a number of risk factors that raise the chances of developing both endometriosis and depression, as well as a variety of gastrointestinal conditions.
While it doesn't rule out an environmental influence, the discovery makes it clear that gut health, endometriosis, and chronic mood disorders often coincide thanks to genes common to all three.
Endometriosis is the presence of endometrial tissue – the thick layers of cells lining the uterus – where it has no business growing.
Just like the endometrium, this tissue is also affected by cyclic fluctuations of hormones, giving rise to internal bleeding, scar tissue, and inflammation. In its most aggressive form it pushes deeply into surrounding organs and tissues, such as the bladder, colon, and ligaments holding muscles in place around said organs.
While endometriosis is thought to affect roughly one in ten women, adding up to around 200 million worldwide, the consequences of this rogue lining vary from being completely asymptomatic to living with chronic, debilitating pelvic pain.
Most commonly the condition makes itself known through a litany of symptoms and conditions, including excessive bleeding, pain during intercourse and during menstruation, nausea, and indigestion.
On top of all that, it's not unusual for people diagnosed with endometriosis to also experience bouts of anxiety and depression. Research backs this up, finding they're the most common disorders found in association with endometriosis.
It's no great leap to presume this relationship is causal. Studies carried out on mice also imply the pain of endometriosis could directly affect the brain, promoting pain sensitisation and mood disorders.
What's more, having higher levels of pelvic pain makes depression even more likely, making it look as if it's the pain that's causing depression, and not endometriosis itself.
Without necessarily contradicting the role of pain in affecting our moods, researchers are becoming increasingly aware of the sheer complexity of depression, finding it's more than a psychological state, but rather a whole physiological system affected by a rich variety of genes.
Twin studies have also hinted strongly at a genetic basis for endometriosis. To see if any of the genes involved might also predispose individuals to depression, researchers made use of data from a genome-wide association study (GWAS) conducted by the International Endogene Consortium.
The sample of more than 208,000 individuals included around 17,000 cases of endometriosis, with just under 192,000 serving as controls, all from a diversity of nations around the globe.
This was compared with a similar GWAS database used previously to find genes linked to depression, with a couple of alternative databases used to see if their findings could be reproduced.
After carrying out an assessment on overlapping mutations common to both, the researchers identified 20 independent locations on the genome which could be considered significant to both conditions, eight of which are completely new.
All up, 22 genes were implied, many with roles in pathways governing adhesion between cells, signalling that regulates cell movements and proliferation, and gastric health.
In fact, additional digging uncovered further causative links between endometriosis and depression and at least one abnormal gut condition, such as peptic ulcers or gastroesophageal reflux disease.
Knowing links can be genetic is one thing. Mapping out the complicated mess of pathways from genes to health and back again, is a whole other story.
We're still a long way off a cure, and even finding suitable treatments is an ongoing challenge. Given we've known about the condition for nearly a century, it's shocking that endometriosis is still so regularly overlooked.
Knowing more about the underlying genetics and how they might play out in other health conditions is beyond worthwhile.
This research was published in Human Genetics.
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November 30, 2020 at 12:28PM
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