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Gene length predicts depression risk
Some people are hit harder by stressful life events than others.
18 July 2003
HELEN PEARSON


Behavioural therapy could help manage stress.
© Corbis


Variation in a single gene may explain why some people weather stressful events while others are plunged into depression, say scientists.

The gene, which encodes a protein called 5-HTT, reveals its influence when people experience divorce, debt, unemployment or other occasions of "threat, loss, humiliation or defeat", Terrie Moffitt of King's College London and her colleagues have shown. They studied nearly 850 New Zealanders taking part in an ongoing health study1.

People carrying two short forms of the 5-HTT gene had a 43% chance of becoming clinically depressed after four or more stressful events experienced between the ages of 21 and 26. This compares with 17% of those with two long ones.

"It's a very profound discovery," says mental-illness researcher Daniel Weinberger of the US National Institute of Mental Health in Bethesda, Maryland. Before this, some genetic studies found a link between 5-HTT type and depression, whereas others did not.

Clinical depression affects an estimated 121 million people worldwide. The American Psychiatric Association defines it as a period of at least two weeks in the year of low mood, plus at least four other symptoms such as sleep changes, reduced energy and a lack of concentration. It is treated with drugs including Prozac, and with behavioural therapy.

Although taxing life events cannot be avoided, the study implies that helping people to manage stress might avert some bouts of depression, says Klaus-Peter Lesch, who studies anxiety at the University of Wurzburg in Germany. "Perhaps it should be more emphasized," he says.

The new results also raise the prospect of genetic tests to predict those who are vulnerable to depression. But this remains unlikely, partly because there is no clear preventative therapy for those at risk.

Such a test would also be unreliable. Of the two-thirds of the general population with one or two short stress-sensitive genes, only a fraction becomes depressed. Many other genes and experiences, such as physical illness, are involved. These must be identified before an accurate risk assessment can be made, warns Moffitt.

Short story

Researchers are not yet sure how stress influences the 5-HTT gene or its protein. The protein pumps the chemical serotonin, which transmits signals between nerve cells, back into cells after use.

People with a short version of the gene have a variation in the gene's control region that causes it to make fewer working serotonin transporters. Stressful events may drive the production of molecules that exacerbate this dearth.

Prozac and other anti-depressants called selective serotonin re-uptake inhibitors (SSRIs) paralyse serotonin transporters so that they pump even less of the chemical into brain cells. Starving cells like this may make them more sensitive to the serotonin that remains.

Weinberger predicts that the finding will spur research into alternative drug targets, such as molecules that interact with the 5-HTT protein. This could avoid the side-effects of SSRIs, which include insomnia and sexual problems. "People have to look beyond this particular protein," he says.

Today's report adds to growing evidence that genes often influence disease only in combination with environmental factors. The same is probably true in other complex conditions - a risk gene for diabetes, for example, may only kick in when a person lives a sedentary lifestyle.


References
Caspi, A. et al. Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. Science, 301, 385 - 389, (2003).


© Nature News Service / Macmillan Magazines Ltd 2003












Monkeys link faces and sounds
Humans may have evolved a language skill from primate ancestors.
26 June 2003
HELEN R. PILCHER


Rhesus monkeys have a repertoire of calls and facial expressions.
© C.T. Miller



Rhesus monkeys can match up sounds and facial expressions, research suggests1. It hints that our capacity to do likewise may have evolved from our primate ancestors.

"Some people had thought that the ability was unique to humans," says Asif Ghazanfar of the Max Planck Institute for Biological Cybernetics, Germany, who studied the monkeys. Other animals had simply not been tested.

In captivity and the wild, rhesus monkeys (Macaca mulatta) produce a variety of noises. "Almost all have a unique facial expression," says Ghazanfar.

Two calls tip the top 15 sounds in the rhesus repertoire. Animals in danger make a short, sharp threatening call - eyes wide, ears flat, mouth wide open. If times are good, they may 'coo', with lips pouting and open just a little.

Ghazanfar showed 11 adult monkeys silent side-by-side videos of threat and coo expressions. When he played the sound of one call, the animals looked straight at the matching face, he found. Over 65% of the monkeys got it right without any training.

Human infants can match voice to face from two months old - long before they have learned to speak. The new results suggest that we may have inherited the trick from primate forebears.


Monkeys identified threat calls with this face.
© A. Ghazanfor



"This skill is critical to language development," says psychologist Janet Werker from the University of British Columbia, Canada, who studies infant speech. "It helps the child figure out who is speaking and where the voice is coming from," she adds.

The findings might also help researchers understand how language is represented in the brain. The vocal and facial components of speech may be represented in intimately linked regions, suggests Werker.


References
Ghazanfar, A. A. & Logothetis, N. K. Facial expressions linked to monkey calls. Nature, 423, 937 - 938, (2003).