the two conditions but also in the clinical entity of mixed anxiety and depression in ICD-10, and the shared genetic risk factors between these two phenomena [2,14]. Our results suggest that 5-HTTLPR is one of the shared genetic factors. However, the fact that its effects on depression act through anxiety and life stress suggests multiple central nervous system actions. Important human neuroimaging findings demonstrated that 5-HTTLPR s allele carriers have greater “tonic” amygdala activation at rest [5], which is in line with our finding of a direct association between 5-HTTLPR and anxiety. Our GxE findings for depression suggest that in addition to tonic, a phasic effect of 5-HTTLPR on emotion processing also exists. Indeed, other brain imaging studies showed increased amygdala response to negative emotional stimuli [4], and indicated an association between the s allele and enhanced acute stress reactivity in a broader brain network [37].
