How the Gene was Found

Over 26 Years of Research Pay Off

Everyone inherits two copies of the serotonin transporter gene, one from each parent. The two versions are created by a slight variation in the sequence of DNA in a region of the gene that acts like a dimmer switch, controlling the level of the gene's turning on and off. This normal genetic variation, or polymorphism, leads to transporters that function somewhat differently. The short variant makes less protein, resulting in increased levels of serotonin in the synapse and prolonged binding of the neurotransmitter to receptors on connecting neurons. Its transporter protein may thus be less efficient at stopping unwanted messages, Moffitt suggests.

Moffitt and colleagues followed 847 Caucasian New Zealanders, born in the early 1970s, from birth into adulthood. Reflecting the approximate mix of the two gene variants in Caucasian populations, 17 percent carried two copies of the stress-sensitive short version, 31 percent two copies of the protective long version, and 51 percent one copy of each version.

Based on clues from studies in knockout mice, monkeys and functional brain imaging in humans, the researchers hypothesized that the short variant predisposed for depression via a "gene-by-environment interaction." They charted study participants' stressful life events�employment, financial, housing, health and relationship woes�from ages 21-26. These included debt problems, homelessness, a disabling injury, and being an abuse victim. Thirty percent had none, 25 percent one, 20 percent two, 11 percent three, and 15 percent four or more such stressful life experiences. When evaluated at age 26, 17 percent of the participants had a diagnosis of major depression in the past year and 3 percent had either attempted or thought about suicide.

Although carriers of the short variant who experienced four or more life stresses represented only 10 percent of the study participants, they accounted for nearly one quarter of the 133 cases of depression. Among those with four or more life stresses, 33 percent with either one or two copies of the short variant�and 43 percent of those with two copies of the short variant�developed depression, compared to 17 percent of those with two copies of the long variant.

Next: The Relationship of Genes & Stress Becomes Clear

Previous: Gene Identified To More Than Doubles Risk Of Depression

Adapted from: Gene More Than Doubles Risk Of Depression Following Life Stresses
(http://www.nimh.nih.gov/press/prgenestress.cfm)

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