It has long been thought that one’s genetic makeup combines with stressors to cause depression, but for many years there was little data to support this hypothesis. This changed in a 2003 paper by Caspi and colleagues, which strongly supported the idea that variation in the serotonin transporter gene, when com- bined with stressors, drastically influ- ences the rate of depression (Caspi A et al., Science 2003;301:386-389). By itself, this variation did not predispose partici- pants to depression. But people with one short allele of “serotonin transporter linked polymorphic region” (5-HTTLPR) were more likely to become depressed in
the face of stressful life events, and peo- ple with two short alleles were even more so. These results supported the popular serotonin theory of depression, since short alleles decrease the produc- tion of the serotonin transporter, lead- ing, presumably, to faulty regulation of serotonin in the synapses. Intrigued by such findings, other scientists attempted to replicate them. A new meta-analysis examined the results of 14 such studies, and found that the short allele result was apparently a chance finding. In fact, only four studies supported the link between the short allele and depressive response to life events, whereas two found oppo- site results (long allele was linked to depressive response to life events), with others finding no consistent link between 5-HTTLPR and depressive response to stress. When the studies were combined, there was no link between the 5-HTTLPR genotype and responding to stressors with depression. (Risch et al., JAMA 2009;301:2462-2471).
TCPR’s Take: Several studies were excluded from the meta-analysis because their measurements were not directly comparable to the original Caspi et al. paper; this could have biased the findings somewhat. However, such exclu- sions happen in most meta-analyses and are unlikely to have altered the results significantly. Given the complexity of our genetic makeup and the frequent failure to replicate psychiatric genetics findings, it is likely wise to wait for consistent replication when a “risk gene” is identified.
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