News archive 2003

Gene helps determine whether the stresses of life push you into depression

17 Jul 2003, PR 50/03

Gene helps determine whether the stresses of life push you into depression, Science study says

Everybody hurts sometimes, everybody cries, but not everybody becomes depressed. New findings suggest that the path to depression depends, in part, on a gene that determines how you react to the stresses of life - the stress of losing a job, a partner, a house, or some combination of these and other possibilities.

A team of psychologists and geneticists, led by Professor Terri Moffitt at the Institute of Psychiatry, King’s College London, describe these findings in the 18 July issue of the journal Science published by AAAS, the science society.

Variations in a region of DNA next to the serotonin transporter gene help to determine whether stressful events will make you depressed. Serotonin is a chemical messenger in the brain. Assuming the same number of stressful life events, people with the least depression-resistant version of the gene are two and a half times more likely to get depressed than people with the most protective version of the gene. These findings reinforce the emerging view that the majority of mental illnesses and other complex diseases cannot be explained by genetic or environmental factors alone, but often arise from an interaction between the two.

"Stressful events tend to come together. People report things like, 'I lost my job, got divorced, and defaulted on my mortgage,'" said Professor Moffitt, the corresponding author on the paper from King's College London, the University of Wisconsin, Madison, and the University of Otago in New Zealand.

Similar strings of unfortunate events are most likely to trigger clinical depression in people with the least protective version of the serotonin transporter gene, according to this research team led by Professors Avshalom Caspi and Terrie Moffitt.

Depression, as defined by the authors, is a period of at least two weeks in the past year when a person falls into a permanently sad, depressed mood. A depressed person loses interest in activities and no longer derives pleasure from life. Their functioning at work and at home significantly diminishes. In addition, a series of other changes in their physical and mental persona, such as sleep problems, must occur for depression to be diagnosed.

The researchers tracked the number of stressful life events that occurred between the 21st and 26th birthdays of participants in a long-term study in New Zealand. They investigated connections between the number of stressful events experienced and the serotonin transporter gene, "5-HTT."

The serotonin transporter gene comes in two versions, "short" and "long." The study revealed that the short version conferred vulnerability to stress, whereas the long version provided protection against stress. The exact role the gene plays in fending off depression remains unclear, according to Moffitt.

Each person carries two copies of the serotonin transporter gene. In the study, of 847 people, 17 percent (147 individuals) carried two short copies, the least protective genetic option, while more than 31 percent (265 individuals) had the most protective possibility. Between these two extremes, 51 percent (435 individuals) carried one stress-sensitive and one protective copy of the gene.

Among study subjects with at least one copy of the short, vulnerability-conferring variant of the 5-HTT gene, who had experienced multiple stressful life events, 33% became depressed. Among study subjects with two copies of the short variant with multiple stressful experiences, 43% became depressed. By comparison, among those with two copies of the protective, long variant, only 17% became depressed.

Including the number of stressful events in their research made the study unique and clarified the connection between the genetic and environmental components of depression, according to Moffitt.

"We now understand the biological basis of some people's ability to bounce back successfully from adverse life events," said Science's deputy editor, life sciences, Katrina Kelner. "This is tremendously exciting. The research adds to the findings published in Science by the same team last year which showed why certain maltreated children grow up to be healthy adults and certain ones develop antisocial behaviors."

Their body of research suggests that subtypes of genes can confer susceptibility to depression and possibly other serious diseases, according to Kelner.

The participants in this study are part of the larger Dunedin Multidisciplinary Health and Development Study, which follows children born between April 1972 and March 1973 in Dunedin, New Zealand. The families of the participants represent the full range of socioeconomic status and health in the general population.

This study reports on emerging depression during young adulthood. New cases of depression peak at this age, making it a good age to monitor, according to Moffitt.

Moffitt hopes that other groups attempt to replicate their findings relatively quickly. She noted that researchers have had trouble replicating past genetics-of-depression studies, possibly because they did not factor in the number of stressful life events prior to the onset of depression.

"We are not reporting a gene that causes a disease. Instead, we believe the gene helps influence whether people are resistant to the negative psychological effects of the unavoidable stresses of life," said Moffitt.

In the past, geneticists have assumed that defects in genes cause disease. In cases like Down's syndrome, a genetic defect is the primary cause the disease.

Moffitt is looking for other alternatives. She suggested that their findings may act as, "a shot in the arm for the field. Once people get the idea that studying environmental risks is a powerful research tool, there ought to be more success in finding undocumented relationships between genes and all sorts of diseases."

The idea, according to Moffitt, is that different versions of genes may provide unequal levels of protection to other unhealthy elements in the environment.

"We looked at stressful experiences, but you can look at any undesirable environmental condition, such as toxic exposure" said Moffitt.

Notes to editors

Avshalom Caspi, Karen Sugden, Terrie Moffitt, Alan Taylor, Ian Craig, Joseph McClay and Jonathan Mill are at King's College London in London, UK. Avshalom Caspi, Terrie Moffitt, and HonaLee Harrington are at U. of Wisconsin in Madison, WI. Judy Martin, Antony Braithwaite, and Richie Poulton are at University of Otago in Dunedin, New Zealand.

Founded in 1848, the American Association for the Advancement of Science (AAAS) has worked to advance science for human well-being through its projects, programs, and publications, in the areas of science policy, science education and international scientific cooperation. AAAS and its journal, Science, report nearly 140,000 individual and institutional subscribers, plus 272 affiliated organizations in more than 130 countries, serving a total of 10 million individuals. Thus, AAAS is the world's largest general federation of scientists. Science is an editorially independent, multidisciplinary, peer-reviewed weekly that ranks among the world's most prestigious scientific journals. AAAS administers EurekAlert!, the online news service, featuring the latest discoveries in science and technology.

King's College London
King’s is one of the oldest and largest colleges of the University of London with some 13,400 undergraduate students and over 5,000 postgraduates in ten schools of study. The College had 24 of its subject-areas awarded the highest rating of 5* and 5 for research quality, demonstrating excellence at an international level. It is in the top group of five universities for research earnings and has an annual turnover of over £300 million and research income from grants and contracts in excess of £90 million (2001-2002).

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