Polymporphism in the serotonin transporter gene have been long known be a risk factor for depression. Serotonergic manipulation has been shown to be different depending on the polymorphism, with opposite effects in patients recovered from depression (rMDD) and controls. Roiser et al (2012, Journal of Psychopharmacology) set out to clarify the neurocognitive mechanisms explaining these results using ATD. Functional magnetic resonance imaging (fMRI) and genotype data were collected. Following ATD or the balanced control mixture, subjects performed an emotional-processing task during fMRI. In the hippocampus and subgenual cingulate, tryptophan depletion increased responses to negative words, relative to positive words, in high-expression controls, previously identified as being at low-risk for mood change following this procedure. Higher-risk low-expression controls and high-expression rMDD subjects however showed the opposite response to tryptophan. An increased neural response to negative words after ATD may reflect an adaptive mechanism promoting resilience to mood change following disturbance of the serotonin system, which is reversed in sub-groups vulnerable to developing depressive symptoms. The interpretation of this data is complicated by the failure to replicate previous findings of increased negative mood following ATD.