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Serotonin would be a nightmare for the post office. The chemical must be delivered to brain cells according to a precise schedule that no one really understands, and some of us get moody when it's not.

The gene involved in transporting serotonin resides on chromosome 17 and has been linked to depression, anxiety, and eating disorders. Slight differences in the genome near the transporter gene have been identified in humans; this variation lies in the so-called promoter region that regulates the gene's activity.

Recent studies have investigated associations between variations in the promoter region and susceptibility to a variety of psychiatric conditions. Although strong evidence of such associations is lacking, serotonin transport is likely to remain a hot topic in research. Prozac™ and similar drugs affect serotonin levels, so both emotions and money are at stake. Here is a sample of serotonin studies.

Ten new variants

Researchers initially characterized the serotonin transporter promoter region a few years ago. The first variants were DNA sequences containing strings of repeated letters, one "short" and one "long". In January, researchers in Japan took a closer look at the promoter region in Japanese and Caucasian subjects and found that short and long may actually be ten novel variants. Interestingly, they also found significant differences in the distributions of the variants between the races. (1)

Short-short and anxiety

In 1999, another group of Japanese researchers reported a link between the short variant and anxiety traits. An analysis of the promoter region in 500 individuals found that people who inherited two copies of the short variant have stronger anxiety-related personality traits than those with long-long or long-short combinations. (2)

Long-long and obsessive-compulsive disorder

Drugs that target serotonin moderate symptoms of obsessive-compulsive disorder (OCD). In 1999, the National Institutes of Mental Health conducted a study to see whether people with OCD inherit a particular combination of variants. The researchers found that people with OCD were more likely than a group of controls to carry two copies of the long variant. Although preliminary, the findings replicated an earlier study among families at risk for the disorder, the researchers said. (3)

Negative results reported

Even when no link has been found between the variants and disorders, some researchers publish results. Last year, for example, U.S. researchers reported that variants in the promoter region did not appear to be a susceptibility factor in autism. Their study looked at the promoter region in 72 autistic subjects and 43 normal subjects. (4)

In February, British researchers said the serotonin promoter region and anorexia nervosa did not appear to be linked in a recent study. An analysis of variants in 138 patients with anorexia and a control group turned up no significant differences. (5)

. . .

1. Nakamura, M. et al. The human serotonin transporter gene linked polymorphism (5-HTTLPR) shows ten novel allelic variants. Mol Psychiatry 1, 32-38 (January 2000).  

2. Murakami, F. et al. Anxiety traits associated with a polymorphism in the serotonin transporter gene regulatory region in the Japanese. J Hum Genet 1, 15-17 (1999).

3. Bengel, D. et al. Association of the serotonin transporter promoter regulatory region polymorphism and obsessive-compulsive disorder. Mol Psychiatry 5, 463-466 (September 1999).

4. Zhong, N. et al. 5-HTTLPR variants not associated with autistic spectrum disorders. Neurogenetics. 2, 129-131 (April 1999).

5. Sundaramurthy, D. et al. Analysis of the serotonin transporter gene linked polymorphism (5-HTTLPR) in anorexia nervosa. Am J Med Genet 1, 53-55 (February 2000).  

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