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Gene Controls Serotonin, a Key to Good Moods

By Edward R. Winstead

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Depression and Bipolar Disorder
Drug Development

The antidepressant Prozac and similar medications are designed to make people feel better by regulating serotonin, a brain chemical involved in emotions and mood. Scientists have now discovered that serotonin levels in the brains of mice vary significantly depending on which form of a particular gene a mouse has.

It is not yet known whether the same gene in humans varies, or whether different variants alter the production of serotonin. But in mice at least, a single genetic variation dramatically changes the amount of serotonin in the brain.

Mice with one form of the gene produced 50 to 70 percent less serotonin than those with another form. The difference is a single letter of DNA, in a gene called Tph2, that varies among mouse strains.

“For the first time, we've identified a naturally occurring genetic difference that controls the production of serotonin in the brain,” Marc Caron, who led the study at Duke University Medical Center in Durham, North Carolina, said in a statement.

The next step will be to screen the human version of the Tph2 gene for variations that affect the production of serotonin. Low levels of serotonin in people have been linked not only to mood disorders but also to problems with sleep and appetite.

Prozac belongs to a class of drugs that helps some people who have abnormally low levels of serotonin. Paxil and Zoloft, often prescribed for depression or anxiety, are other members of this class, known as selective serotonin re-uptake inhibitors, or SSRIs.

The Duke researchers tracked serotonin in mice that had different forms of the Tph2 gene, which makes an enzyme that synthesizes serotonin. Discovered last year, this gene is similar to another gene that synthesizes serotonin, called Tph1.

The finding, published tomorrow in Science, may help other scientists who are using these mouse strains in their research. The rodents, like some of their human counterparts, behave differently in part because their brains produce different amounts of serotonin.

Zhang, X. et al. Tryptophan Hydroxylase-2 Controls Brain Serotonin Synthesis. Science 305, 217 (July 9, 2004).

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