Researchers hope that the discovery could lead to new treatments and early diagnosis of the condition that affects one in five people in Britain during their lifetime.
The team at Yale University have found that a gene called MKP-1 is twice as active in those that are depressed than those with good mental health.
When activated the gene appears to blocks pathways crucial to the survival and function of neurons in the brain.
Neurons are used to transfer and process information across the brain by a process of electrical and chemical signaling.
Professor Ronald Duman, the study leader, said it was "particularly exciting" because of the genes link with maintaining healthy brain function.
"This could be a primary cause, or at least a major contributing factor, to the signalling abnormalities that lead to depression," he said
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