WHETHER you bounce back from life’s nasty shocks or sink into deep despair depends largely on which version you have of a gene involved in serotonin regulation. People with one form seem to be more vulnerable to depression, according to a study published last week.
If the mechanism of the gene’s influence on mental illness can be understood, it might be possible to develop treatments that make people less vulnerable to depression after stressful events. More immediately, the discovery raises the prospect of genetic tests to identify people at high risk of becoming severely depressed.
A key feature of the study is that it takes into account people’s life experiences as well their genetic make-up (Science, vol 301, p 386). Previous attempts to find more direct links between gene variants and psychiatric disorders have often encountered difficulties. “This study shows it’s important to try to find genes for risk of mental illness, rather than the gene for illness itself,” says Ian Goodyer, a depression expert at the University of Cambridge.
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In the study, a team led by Terrie Moffitt of King’s College London recorded the number of stressful events, such as losing a job or a partner, that 847 white New Zealanders had experienced between the ages of 21 and 26. The researchers looked at whether the subjects became severely depressed as a result, and also which versions they had of a gene that affects levels of the neurotransmitter serotonin.
The control region for the gene comes in either a short or a long form. The long form results in increased production of a protein that transports serotonin back into neurons, and so lowers levels in synapses. This serotonin transporter protein is the target of Prozac-like antidepressants, but its overall effects on mood are not clear-cut.
The team found that people with two long copies of the gene had the same relatively low rates of depression regardless of how many traumatic events they had endured. Those with one short and one long copy were more likely to become depressed, and having two short versions was worst of all (see Graph). About 30 per cent of people have two long genes, 50 per cent have one of each, and 20 per cent have two short ones.
Moffit’s team has previously shown that another gene interacts with life experiences to determine behaviour patterns (91av, 10 August 2002, p 25). In this case, men with a particular gene variant coupled with an abusive childhood were more likely to become violent adults.
The strategy of searching for vulnerability genes should extend beyond psychiatric diseases, says Moffitt. “Presumably there are genetic risk factors for lead poisoning, tobacco and dietary fat,” she says. “But it will take some time to find the candidate genes.”