July 17, 2003 — Why do life’s stresses send some into depression while others recover more easily? A new study shows that genetic makeup can double a person’s vulnerability to depression.

The study, published in this week’s Science, describes variations in a gene called 5-HTT, which regulates levels of serotonin, a brain chemical.

People with short versions of this gene were more likely to develop depression and suicidal tendencies in response to life stresses than people with a long version of the gene, writes lead researcher Avshalom Caspi, MD, a psychiatrist with King’s College in London.

It’s more evidence that a person’s response to life is altered by his or her genetic makeup, writes Caspi.

Although the 5-HTT gene may not be directly associated with depression, it could moderate the amount of serotonin released in response to stress, he writes.

Genes Determine Vulnerability

In their study, Caspi and colleagues followed 847 children, born in the early 1970s, from birth to adulthood. Genetic studies showed that 17% had two copies of the stress-sensitive short version; 31% had two copies of the protective long version, and 51% had one copy of each version.

Researchers charted stressful life events when the children grew up — from ages 21 to 26 — such as employment, financial, housing, health, and relationship problems. Among their problems were debt, homelessness, disabling injury, and abuse.

Among the young adults:

• 30% had experienced no stressful life events, 25% had one event, 20% had two events, 11% had three events, and 15% had four or more events. There was no difference in the number of stressful life events between the groups that had the different genes.
• At age 26, 17% had developed major depression and 3% had either attempted or thought about suicide.
• 10% with the short gene — and who experienced four or more life stresses — accounted for nearly 25% of the 133 cases of depression.

Among those who had four or more life stresses:

• 33% with one or two copies of the short gene developed depression.
• 43% with two short-gene copies developed depression.
• 11% with the short gene considered or attempted suicide.
• 17% with two copies of the long gene did not develop depression.
• 4% with the long gene considered suicide.

Also, those who had stressful live events before age 10 — such as abuse — were more likely to be depressed as adults.

“Because the gene is present from conception, it would have been very suspicious if it did not affect response to stress in childhood,” says co-author Terry Moffitt, PhD, a psychologist at the University of Wisconsin-Madison, in a news release. “The fact that it interacts with childhood maltreatment helps to demonstrate that the finding is strong.”

The finding could lead to new therapies or diagnostic tests for vulnerability to depression, he says.