While this meta-analysis focused specifically on observational studies specifically assessing whether 5-HTTLPR moderates the relationship between stress and depression, the results we found are consistent with a broad range of studies exploring the relationship between functional serotonin transporter genetic variation and stress in different ways. Experimental neuroscience studies have found consistent evidence that 5-HTTLPR s allele carriers demonstrate a more pronounced amygdala and HPA axis response to affective or threatening stimuli 75–77. In addition, non-human primates studies that have found increased stress sensitivity among individuals with a low functioning serotonin transporter allele78, 79. Together, these lines of evidence provide clear and converging evidence that 5-HTTLPR plays a role in moderating the response to stress. It is also clear from these studies however, that this variant explains only a small proportion of the genetic variance relevant to stress response. The successes and failures of the studies exploring the 5-HTTLPR variant included in this analysis should guide our future work as we try to develop a broader understanding of the genetic architecture that moderates the relationship between stress and depression.
