Genes-Environment interactions in predicting adolescent depression: Effects of sex and stress type.

By Nestor Lopez-Duran PhD

Many of you have probably heard that studies have identified specific gene variations that when interacting with stressors in the environment increase the risk of developing depression. This interaction has been used by researchers and clinicians to explain why some people become depressed when exposed to stressful events, while others appear resilient. The argument is that people differ in how susceptible they are to stressors because of their genetic profile. Those with a particular variation in some genes may be more susceptible to the stressors while others with a different variation may be less susceptible.  Most of this research has been focused on a variation in a Serotonin transporter gene. A variation is called a polymorphism, and this refers to areas of a gene that differ between people. Variations (polymorphism) are what makes us unique, since most of our genetic makeup is actually identical. In the case of the Serotonin transporter gene, there are two variants of one specific variation usually called the short and the long alleles. Since we have two alleles of the same variation, people may have 1) two long alleles; 2) one long and one short allele; and 3) two short alleles. These short alleles have been the focus of research interest because some studies have found that people who have the short allele are more susceptible to stress than people who have the long allele. Yet, there are a few limitations with the existing research. First, several studies have failed to replicate these findings. That is, some studies have not found an association between these gene variation and susceptibility to stress. Second, most of these studies have been done with adults, and we dont know if children and adolescents with the short allele also show a susceptibility to stressors.

A study by the renown depression researcher Contance Hammen at UCLA, to be published in the Journal of Child Psychology and Psychiatry, may help us clarify some of these issues. Dr. Hammen wanted to examine whether differences in the way stress has been defined and measured by previous studies may explain the inconsistency of their findings. For example, some studies have focused on acute stressors (divorce, death of a family member, etc) while others have focused on chronic stressors (severe poverty, exposure to chronic abuse, etc). It is then possible that one type of stress- but not others -interact with a persons genetic profile to increase the risk for depression. Thus in this study, the authors examined 346 adolescents who were evaluated at age 16 and 20.  The authors assessed for depression symptoms, genetic profile, and the history of exposure to acute and chronic stressors.

The results:

Surprisingly, the authors found that acute events did not interact with the participants genetic profile to predict depression. So it didnt matter whether an adolescent had two long alleles, one short and one long, or two short alleles. Regardless of the variants of these alleles, exposure of acute stress was associated with higher depressive symptoms.

The results for chronic stressors were more interesting. While chronic stressors also predicted depression, this effect depended on two things: The genetic profile of the person and whether the person was a male or a female.

Susceptibility to Chronic Stress by Genotype

As you can see on the graphic above, for females, those who had at least one short allele showed increases in depression scores (y axis) as the level of chronic stress increased ( x axis). In contrast, the solid line represent those who had two long alleles. These individuals did not show an increase in depression scores as their chronic stress increased. That is, these individuals appear to be resilient to the effects of chronic stress. A similar pattern was found for the boys, but such a pattern was not statistically significant, and thus we cant tell for sure whether the effect also applies to males.

In conclusion, the results of this study support previous findings indicating that there is an interaction between our environment and our genes in that particular variants of a serotonin polymorphism may make people more susceptible or more resilient to the effect of chronic (but not acute) stress, and that this effect appears to be stronger for girls than boys.

The reference: Hammen, C., Brennan, P., Keenan-Miller, D., Hazel, N., & Najman, J. (2009). Chronic and acute stress, gender, and serotonin transporter gene-environment interactions predicting depression symptoms in youth Journal of Child Psychology and Psychiatry DOI: 10.1111/j.1469-7610.2009.02177.x