by Joye C. Anestis
This past week, a section of the psychological/psychiatric community exploded as some divisive new findings were published by JAMA questioning the previously lauded link between the serotonin transporter gene and depression. News outlets latched on to this reports with headlines like "Report on Gene for Depression is Now Faulted" and "Sad News for 'Depression Gene.'" For those of you who missed the excitement, I thought I'd summarize the new study for you.
But first a little background on this issue. The majority of the mental health field believes in a diathesis-stress model of mental illness. Supported by a plethora of empirical studies demonstrating clear heritability for most mental illnesses, the diathesis-stress model argues that some individuals have a predisposition (the diathesis) for developing a mental illness, but the mental illness is not developed unless some environmental stressor activates the diathesis. Put another way, if you have a diathesis for a mental illness (for example, a genetic risk or some other biological factor), you will not develop that mental illness until some stress, or combination of stresses, triggers it. Many scientists have been attempting to identify the various diatheses which contribute to the development of specific mental illnesses.
One such diathesis that has been proposed is the serotonin transporter gene (5-HTT). Caspi and colleagues (2003) first reported on its potential function to predispose individuals to depression. Particularly, they demonstrated that variation in the promoter region of the serotonin transporter gene, only in interaction with stressful life events, plays a role in the development of depression. The link also makes some logical sense when you remember that many effective antidepressants modulate serotonin expression (they are called serotonin reuptake inhibitors) and the well-established link between negative life events and depression. As you can imagine, this finding was huge! And other researchers quickly began attempting to replicate this finding.
At this time, enough research has been conducted to justify a meta-analysis of the data. Meta-analysis is a statistical technique used to summarize a group of studies on a specific topic. You can think of it as a form of averaging; you take the effects found in different studies and find the average size of the effect across all of these studies. Neil Risch and colleagues (2009) searched for all of the studies investigating the serotonin transporter gene, life stresses, and depression. They ended up with 24 studies. Two meta-analyses were done, one utilizing all the participant data (14 studies, n = 14, 250) and one examining sex-specific outcomes (n = 10, 943). The investigators found a direct link between the number of stressful life events and depression in these studies, both in the combined sample and when the analyses were conducted by sex. A direct link between the serotonin transporter gene alone and depression was not found in the the combined sample or the sex-specific sample. When the interaction between the gene and life stress was examined, the results did not support this particular interaction predicting depression in males alone, females alone, or when both sexes were combined. In sum, life stresses significantly predict the development of depression, but the serotonin transporter gene or the interaction between life stress and the gene do not...at least at this time, as analyzed in this study.
I am sure that in the coming weeks and months, many rebuttal papers will be published arguing the validity and invalidity of these findings. I believe there are several important messages we can take home from this meta-analysis, but I believe the most important is: these inconclusive findings in no way argue that genes and other biological factors do not influence the development of depression. The Risch study only questions the effect of one particular gene. There are many many others that may be playing a role and we may not yet have sophisticated enough techniques to fully understand the role of specific genes. There may be more nuanced facets of the serotonin transporter gene that are not detected in all studies. There are a plethora of plausible explanations. When studying illnesses for which there are no pathognomonic diagnostic markers, it is incredibly difficult to pinpoint biological and genetic influences, but we are getting closer and closer to doing so.