New research on depression has demystified decades of work that have distinguished individual genes responsible for the main mood disorder.
This is not to say that depression is not passed on by families – but it means that any genes that might play a role do not act alone.
The analysis of more than 620,000 people by researchers from across the United States is the largest and most comprehensive study of its kind. After intensive research, the team arrived empty-handed.
"This study confirms that efforts to find a single gene or a handful of genes that determine depression are failing," says geneticist Richard Border of the University of Colorado at Boulder.
His conclusion is a blow to all clinical agencies hoping to create diagnostic tools and treatments based on the belief that depression is the result of something as simple as a few broken genes.
For over 20 years, researchers suspect chronic mood disorders such as anxiety and depression to root in the dysfunction of cellular transport systems in the brain.
By digging deeper, the genes responsible for regulating the uptake of neurotransmitters such as serotonin have been widely blamed, suggesting a mutation or two, and perhaps a point exposure to trauma, are enough to risk a serious mental illness.
A number of studies in recent years have screened genebanks to look for possible relationships between mood disorders and genetic "modifications" called single nucleotide polymorphisms, only finding no shortage of candidates.
It's an alluring idea, promising that genetic testing could tell us who could benefit from custom-made pharmaceuticals targeting the deficit.
Maybe it's too good to be true after all.
"Whenever someone claims to have identified the gene that" causes "a complex trait, it's a moment of skepticism," Border said.
The researchers did not test every DNA modification ever claimed to be responsible for depression, but only the 18 most likely candidates, who appeared at least 10 times in the literature.
By browsing databases belonging to 23andMe, the Genomics Psychiatry Consortium and the British Biobank, the researchers assembled a genetic sample covering more than half a million individuals.
They included various measures of mood disturbance and used a range of statistical measures to identify potential links between these 18 genetic differences and depression.
The researchers even took into account potential variations that required some kind of environmental trigger, such as socio-economic adversity or sexual abuse. Nothing stands out.
"We found that, overall, these candidate genes are not more related to depression than to any random gene," says Matthew Keller, neuroscientist at the University. from Colorado to Boulder.
"We are not saying that depression is not hereditary at all. This is what we say is that depression is influenced by many variations and that each of them has a tiny effect.
This means that we still have good reasons to continue to study our DNA to identify the causes of depression, but we can not focus solely on single genes. Researchers must instead seek collaborative networks.
If geneticists do not find such simple links, the researchers are eager to point this out. Assumptions based on the fundamental relationships between behavior and candidate genes are generally known to be erroneous.
But other areas have been less critical, they claim, leaving hope that we will find examples of a "depression gene." It is time to move on.
"It's like in" The emperor does not wear clothes. "There is nothing there," Keller said.
"I hope it's the last nail in the coffin for this kind of studies."
This research was published in the American Journal of Psychiatry.