Bound for Gloom and Doom?

A tendency towards anxiety and depression may be linked to overactivity in the brain's fear center, according to a new study that strengthens the connection between genes and psychological disorders.

Pinning mental illness on specific genes is among the most difficult tasks for behavioral scientists. Three years ago, researchers made a rare link between depression and a gene that regulates the neurotransmitter serotonin: People with a short version of the gene, called 5-HTT, are more likely to become anxious or depressed when confronted with a bad experience--such as a death in the family--than are those with a long version (ScienceNOW, 18 July 2003). But what are the brain mechanisms involved?

A team led by psychologist Turhan Canli at Stony Brook University in New York used a combination of tests to find out. They scanned the brains of 48 subjects--16 with two long versions of the gene, and 32 with at least one short version. When in a "resting" state, the subjects with short versions showed more activity in both the amygdala, the brain's fear center, and the hippocampus, a memory center connected to it, than when they saw a picture of a person with a neutral facial expression. In the long-version group, the effect was just the opposite: Subjects showed little amygdala or hippocampus activation in the resting state, but they responded with more activity to the neutral face.

Scientists had assumed that some brain areas in people with the short versions of the 5-HTT gene are more responsive to stress. But the new findings indicate that people with the short version may have a chronically higher background level of activity, says Canli, whose team reports its findings online this week in Proceedings of the National Academy of Sciences.

That means that people who carry the short version are never free from uncertainty over potential threats, says psychiatrist Daniel Weinberger at the National Institute of Mental Health in Bethesda, Maryland. As a result, it takes less to send these people over the top into depressive or anxious states. Or, as Terrie Moffitt, a psychologist at the Institute of Psychiatry in London who helped draw the link between 5-HTT and depression, puts it: "They wear grey-colored glasses, whereas people with the long 5-HTT genotype wear rose-colored glasses."

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