‘Gene Map for Depression’ Opens Doors to New Treatments
There are now raised hopes for more effective treatments for depression, a condition that affects over 300 million people globally.
In the world’s largest investigation into the impact of DNA on the mental disorder, more than 200 researchers identified 44 gene variants that raise the risk of depression. This includes 30 that have never been connected to the condition before.
Through tripling the number of gene regions linked to depression, scientists hope to understand more about why the disorder affects some but not others, even when they have similar life experiences. Such work could also support the search for drugs to treat the conditions which affects as many as one in four people over a lifetime.
“If you have a lower genetic burden of depression, perhaps you are more resistant to the stresses we all experience in life,” explained Cathryn Lewis, professor of statistical genetics and a senior author on the study at King’s College London.
In the study itself, the researchers pooled seven separate datasets from the U.K., the U.S., Iceland, and Denmark, to obtain genetic information on 135,000 people who reported having depression, and 345,000 mentally healthy individuals. Later, the scientists compared DNA across the groups to find gene variants that were more common in those with depression.
The results revealed a substantial overlap in the genetics that underpins depression and other mental disorders such as anxiety, schizophrenia, and bipolar disorder, but also body mass index, where DNA that predisposes people to obesity also raises the risk of depression. The results of the study have been published in the journal Nature Genetics.
Many of the genes in the study play a role in how neurons grow, operate and send signals around the brain, where two regions are known as the prefrontal cortex and the anterior cingulate cortex are the most important for depression.
Co-author on the paper, Gerome Breen, said that some of the gene variants they found are linked to neurotransmitters such as serotonin, which existing antidepressants work on. However, other gene variants point to new biological mechanisms that the next generation of drugs might target.
“What we’ve had in recent decades is a shortage of new mechanisms that underlie depression and psychiatric disorders,” he said. “The hope is that in new data we identify new processes that can be targeted by newly developed types of drugs, which have different mechanisms of action to existing medications.”
Although it will take more research to confirm that the gene variants found in the study are really linked to depression, many of the participants involved in the research self-reported depression, which is far less reliable than a clinical diagnosis. This means that some of the gene variants the scientists link to depression could turn out not to be involved in the disorder.
Jonathan Flint, who studies the genetics of depression at the University of California in Los Angeles, said, “Our current treatments for depression are relatively ineffective – roughly speaking, only about half of patients improve – so we really need better therapies. To discover new treatments and to deliver the ones we have more effectively, we need a better understanding of what causes depression. Finding genetic variants is a way to do just that – the risk variants point to genes that are involved in the disease, and thus provide clues to how depression arises.”
It’s important to bear in mind that although 44 variants were linked to depression, this is only a fraction of the total because many more will have had too small an effect to be discovered in the latest study. “We know that thousands of genes are involved in depression with each having a very modest effect on a person’s risk,” concluded Lewis. “There is certainly no single gene for depression.”