The idea of a "depression gene" has captured the imaginations of some scientists for decades. Over the past 20 years, literally hundreds of studies have hinted that people with a variation of just a few select genes are at a significantly greater risk of depression.

However, a bold new study has suggested this mounting heap of research might have been heading down the wrong track towards a dead end. Confirming the doubts of previous research, they argue that the idea of "depression genes" is a total dud.

Using data on over 620,000 individuals, the biggest study of its kind concluded that 18 candidate genes for depression actually have little to no role in the development of depression. Reporting in last month’s issue of The American Journal Of Psychiatry, the study authors call on the scientific community to abandon the "candidate gene hypotheses” for depression.

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

“It's like in 'The Emperor Wears No Clothes.' There's just nothing there," added senior author Matthew Keller, an associate professor of Psychology and Neuroscience. "I hope this is the final nail in the coffin for those kinds of studies."

One of the most promising candidate genes was a “short” variation of 5-HTTLPR in the gene SLC6A4. Known to play a role in the transportation of the feel-good neurotransmitter serotonin, the gene has been the focus of over 450 scientific studies, the majority of which found a promising association with depression, especially when exposed to trauma in early life. Ever since this link was identified in 1996, hundreds of studies – often with relatively small sample sizes – have attempted to home in on a small set of other "depression genes".

However, the study found that SLC6A4 and the 17 other “depression genes” were no more related to depression than any other randomly selected gene. 

This isn’t to say that depression doesn’t have some kind of genetic underpinning. Instead, the study authors argue that the genetic link to depression is considerably more complex and fiddly than just a small handful of genes. The research hopes to build on mounting doubts about “depression genes” and finally dispose of the myth of the candidate gene hypothesis for depression – the idea that a variation on a single gene relates to the condition based on findings from previous studies. Even beyond the hard-coded elements of genetics, we then have to consider the less-quantifiable environmental factors that can play a role in mental health and meddle with genes too.

The truth, as they say, resists simplicity.

"Any time someone claims to have identified the gene that 'causes' a complex trait is a time to be skeptical," Border concluded.