A new study reports finding no convincing evidence that depression is governed by a single gene or group of genes.

Fallen girl.

Image via Pixabay.

Several studies published over the last two decades or so seemed to point to a link between genetics and depression. Namely, the results suggested that a small set of particular genes or gene-variants has a large part to play in making us more susceptible to depression. These results obviously sparked hope that depression might be weeded out through a combination of genetic testing and medication.

However, a study from the University of Colorado Boulder says those studies only found “false positives”.

No genes for that

“This study confirms that efforts to find a single gene or handful of genes which determine depression are doomed to fail,” said lead author Richard Border, a graduate student and researcher at the Institute for Behavioral Genetics.

Border’s team assessed genetic and survey data from 620,000 individuals via the UK Biobank, 23andMe, and the Psychiatric Genomics Consortium. According to them, this was the largest and most comprehensive investigation to date on the link between genes and depression. All in all, they report, the team didn’t find any evidence that the previously-identified genes are any more or less associated with depression than randomly-chosen genes. This would suggest that the previous studies were false positives and that the scientific community should abandon what are known as “candidate gene hypotheses,” the authors conclude.

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The team looked at the 18 candidate genes that have appeared at least 10 times in depression-focused studies. One among them, a gene called SLC6A4, is involved in the transport of the neurochemical serotonin. Past research has found that people with a certain ‘short’ version of this gene have a significantly higher risk of developing depression, especially when they experienced trauma in their early life. They also looked at those genes involved in the production of brain-derived neurotrophic factor (BDNF) — a protein involved in nerve formation — and the neurotransmitter dopamine.

“We found that, as a set, these candidate genes are no more related to depression than any random gene out there,” said senior author Matthew Keller, an associate professor of Psychology and Neuroscience. “The results, even to us, were a little bit stunning.”

“We are not saying that depression is not heritable at all. It is. What we are saying is that depression is influenced by many many variants, and individually each of those has a miniscule effect.”

The team stresses that the findings don’t mean we should stop looking into a genetic root for depression — simply that we have to accept that this issue is much more complicated than we’d like to believe. There are likely thousands of genes that contribute in one way or another to depression. Ultimately, we’ll probably be able to calculate accurate “polygenic scores” to predict depression risk in individuals, even potentially develop drugs designed to counteract that risk, but there’s still a lot of work we have to do before that.

In the meantime, Border says, consumers should be wary of claims that individual genes have large effects on complex behaviors. While the risk of some medical conditions, like breast cancer and Alzheimer’s disease, has been clearly linked to individual genes, it’s not so simple with traits like depression.

“Any time someone claims to have identified the gene that ’causes’ a complex trait is a time to be skeptical,” said Border.

That’s solid advice whenever someone claims anything, honestly.

The paper “No Support for Historical Candidate Gene or Candidate Gene-by-Interaction Hypotheses for Major Depression Across Multiple Large Samples” has been published in the American Journal of Psychiatry.