US researchers have identified a genetic variation in mice that affects levels of the 'feel-good' brain chemical serotonin. The study, published in the journal Science, could shed light on why some people are prone to depression and other mood disorders. The findings could also help explain why some patients respond well to anti-depressants such as Prozac, which aim to boost brain serotonin levels, while others do not.
Serotonin is a neurotransmitter, a chemical that enables brain cells to communicate with each other. Scientists have long known that levels of serotonin are linked to feelings of emotional well-being - a study published last year showed that a gene involved in serotonin production appears to affect a person's ability to cope with stressful life events. However, the latest study is the first to identify a genetic difference that directly affects levels of serotonin in the brain.
The researchers, based at Duke University Medical School, looked at two different versions of a mouse gene called Tph2. They found that one version was linked to a reduction in the level of brain serotonin of between 50 to 70 per cent. The findings suggest that 'there really are heritable differences in how the brain makes or synthesises serotonin', commented Jerrold Rosenbaum, chief of psychiatry at Massachusetts General Hospital in Boston. 'It gives us a whole new line of inquiry, both as to tailored treatment and to understanding how treatments work, and why there are differences in response', he added.
Patients with depression are often prescribed drugs that boost serotonin levels, called selective serotonin reuptake inhibitors (SSRIs), of which Prozac is one. But according to Rosenbaum, 'only 30 to 40 per cent of people given an SSRI really get a high quality response' from the drug. The Duke scientists are now looking for similar genetic differences in humans; research that could eventually lead to 'psychiatric pharmacogenetics', says team leader Marc Caron. By identifying these differences, 'doctors will be able to predict in advance who'll respond to a serotonin-augmenting drug and who is less likely to do so, so you could spare the person ineffective trials or side effects', he said.