Depression will affect one in every five people, with 121 million individuals now suffering from the disease worldwide. Anecdotal evidence from behavioural genetics has indicated that people at risk from depression might have more extreme reactions to stressful events, such as bereavement, owing to their genetic background. Now, thanks to recent work by Terrie Moffitt and colleagues, it seems that a polymorphism in the promoter of a gene that encodes a serotonin transporter can exacerbate the effects of stress on depression.

The specific genes that are involved in modulating any link between stress and depression have remained, until now, unidentified. Work in mice and rhesus macaques, and neuroimaging of human brains, have indicated an association between an allele of 5-HTT (SLC6A4), which is the serotonin transporter, and reactions to stressful conditions, although the link to depression was not conclusive. 5-HTT is located on 17q11.2 and is modified by sequence elements in the 5-HTT gene-linked polymorphic region (5-HTTLPR). This alteration in the promoter sequence leads to two variants of 5-HTT: the short allele, which has lower transcriptional efficiency, and the long allele. 5-HTT works in conjunction with a set of genes that are targeted by most antidepressants to control serotonin uptake, particularly at the brain synapse.

Moffitt and colleagues have now shown a clear gene–environment (G × E) link between the short 5-HTT variant and an increased risk of depression following stressful experiences. The authors studied a group of children in New Zealand from birth. They showed that there was an increased risk of depression at 26 years of age, following at least four stressful life events between the ages of 21 and 26, if the adult had inherited at least one copy of the short allele. Individuals with two copies of the long allele were just as likely to encounter stressful events during their lifetime, but were at significantly lower risk of developing depression.

It is common knowledge that some people seem more able to cope with the trials and tribulations of everyday life. This research points us towards the association of stress and depression at a genetic level. As at least 50% of Caucasians carry one copy of the short 5-HTT allele, it is worth investigating this interaction more closely to aid those who are most at risk from developing depression.