A genetic variation may determine whether people are prone to depression, scientists have suggested.
The research could help indicate who will experience depression
A team from Duke University Medical Center, US, found mice had two versions of an enzyme which controls levels of the brain chemical serotonin.
They say humans may have many more versions of the enzyme, explaining why some are depressed and others are not.
Writing in Science, they say a genetic test may predict who is likely to benefit from medication.
Serotonin is a chemical used to transmit messages between nerve cells in the brain.
Levels of the chemical have been linked to conditions including depression, anxiety, post-traumatic stress disorder and attention deficit hyperactivity disorder.
Scientists discovered last year that the enzyme Tph2 (typtophan hydroxylase-2), was present in the brain, and played a role in controlling serotonin levels.
In this latest research, they screened mouse brains to look for the gene which controlled production of the enzyme.
They were surprised to find two different versions of the gene.
When researchers looked at the effects of the enzyme variants in the lab, it was found they had a major effect on the amount of serotonin the cells produce.
Mice with one variant produced 50 to 70% less serotonin in their brains than did mice with the other variant.
The scientists said their findings in mice could lead to new insights into the role the enzyme, and the gene that controls it, might play in animal behaviour and human psychiatric disorders.
Dr Xiadong Zhang, the lead researcher on the study, said: "This single genetic difference has a huge impact on serotonin levels, confirming that the gene is fundamental in the synthesis of brain serotonin."
They suggest the enzyme could also affect how patients respond to selective serotonin re-uptake inhibitors (SSRIs), such as Prozac.
It may also be possible to develop a genetic test to distinguish which version of the gene a patient has, and therefore predict how a patient will respond to the drugs.
Marc Caron, professor of cell biology at Duke University Medical Center, who also worked on the study, said: "For the first time, we've identified a naturally occurring genetic difference that controls the production of serotonin in the brain."
The researchers now plan to look at genetic differences in humans, and how they may influence brain chemistry.
Professor Caron said he suspected humans carried many more versions of the serotonin gene
Marjorie Wallace, chief executive of the mental health charity Sane: "We are excited by the findings of this study, which may hold promise for our understanding of mental illness.
"This kind of research is vital because it is yet more evidence that depression may be linked to genetic vulnerability and so could remove the blame and guilt that so many people and families feel."
She added: "Only by understanding how drugs are working in the brains of those affected can we target treatment to individuals and provide effective medication to relieve the symptoms and side effects which are the cause of so much current concern."