Our analysis raises several important issues that require further research. One question, which we are beginning to explore, is how the transcriptional efficiency of the XL allele compares with that of the S and L alleles. Additional laboratory research is needed to identify the functional importance of other alleles of the 5-HTTLPR polymorphism. In addition, our findings suggest that Risch and colleagues’ [9] failure to find evidence of an interaction between 5-HTTLPR and stressful life events on depression may be premature. Community-based studies based on large and diverse samples, with detailed genotyping of 5-HTTLPR variants, are necessary to identify more precisely the nature of the association between the serotonin transporter genotype and depression, as well as potential variability by the severity of stressful experience and ethnicity. It seems virtually certain that the links between 5-HTTLPR and depression are more complex than previously thought.
