Study Brings New Concept of 'Risk' Gene, Environment's Role

BioWOrld Today Science Editor

It's a rare paper that is published by the Proceedings of the National Academy of Sciences under two section headings. And rarer still when those two sections are Genetics and Social Sciences.

But that's what happened this week with a paper on the "role of mother's genes and environment in postpartum depression."

The paper revisits well-trodden, if hotly contested, ground: the question of whether people with certain variants of the serotonin transporter are more likely to become depressed in response to stressful life experiences. (See BioWorld Today, Jan. 5, 2011.)

The serotonin transporter, lead author Colter Mitchell told BioWorld Today, is "one of the most studied polymorphisms in depression research, and probably the most studied polymorphism in gene-environment interaction studies."

But Mitchell and his team have given the science a new twist, by suggesting a new concept for how serotonin transporter variants might interact with stress.

The classical view is that genes either increase or decrease a person's risk of developing disease. In the case of the serotonin transporter, that would mean that some variants predispose their carriers to developing depression in response to stressful life experiences.

But Mitchell and his team think that some gene variants make their carriers more susceptible to environmental influences – whether those influences are positive or negative.

"For some people, it doesn't seem to make a difference what environment they are in," he said. But others "really suffer quite a bit . . . if they are in a bad environment."

Mitchell is a sociologist at Princeton University and the first author of the paper, which was published online May 16, 2011.

Mitchell and his team tested their idea by looking at whether the interaction between serotonin transporter variants and socioeconomic status affected their chances of developing postpartum depression.

If certain transporter variants make their carriers more susceptible to environmental influences, then those women should be more likely to develop postpartum depression if their socioeconomic status is low, and less likely if it is high. And looking at two genetic variants within the serotonin transporter, that is indeed what the team found. On the average, every year of education decreased a woman's chances of developing postpartum depression by roughly 18 percent – if she had the gene variant that made her, in the researchers' interpretation, sensitive to environmental effects.

For women who did not have the sensitive gene variants, there was no relationship between education level and the risk of postpartum depression. Altogether, this meant that women with reactive gene variants were more likely to be depressed than those without if their education levels were low, but protected from depression at high education levels.

Mitchell and his colleagues want to look at additional variants in the serotonin transporter to see whether they have similar effects to the two variants his team studied, and look at maternal depression rates for longer time periods.

The authors used years of education as a stand-in for socioeconomic status. Socioeconomic status, in turn, was itself a stand-in for stress level.

Mitchell said that although education is two steps away from stress levels, their link is nevertheless strong.

"In the U.S., not having a high school degree is really associated with a difficult life," he said, and low socioeconomic status is associated with stress both subjectively – people report feeling more stressed – and objectively, as measured by stress hormone levels.

Socioeconomic status is determined not just by education, but also by income. But, he noted, given that the women in the study were new mothers, "income is probably a lot more volatile for them at this time," and so the team decided to look at education levels as a more stable measure.

Mitchell said that the results fit with recent studies showing that there is a gene-environment interaction between stress, the serotonin transporter and risk of depression.

Mitchell said that his team's findings may explain the discrepancies between earlier studies on the same interaction, some of which replicated the original results and some of which did not.

His team's work suggested that rather than some genetic variants, rather than raising or lowering disease risk, predispose their owners to be more sensitive to their environment, for better or for worse.

The work now published in PNAS suggested that scientific studies "select on [socioeconomic status] a lot more than they think sometimes" – and that for the research on serotonin transporters, those selection biases ultimately had an effect on the results.

For biomedical scientists, in fact, the results could be seen as a call to scientists to pay attention to socioeconomic factors that affect their research subjects.

While the low end of the socioeconomic spectrum, also known as poverty, has well-documented influences on health, the results demonstrated that to make sense of complex health issues such as depression, "looking at a positive environment is really pretty important as well . . . a lack of stress and a positive environment are not the same thing," Mitchell added.

Published: May 18, 2011