In healthy individuals, differential amygdala reactivity to negative stimuli could represent an intermediate phenotype associated with vulnerability to anxiety and depressive disorders60. Indeed, several studies have linked the short allele of 5-HTTLPR and the Met158 allele of COMT with higher anxiety levels, vulnerability to negative mood, increased amygdala reactivity to negative stimuli and altered functional coupling between the amygdala and the cortex50,51,103,104. Furthermore, individual differences in cortico-limbic connectivity suggest that some people might have a genetic predisposition to inflexible emotion processing103. As mentioned above, recent imaging studies have shown evidence that multiple gene interactions have an effect on limbic reactivity to unpleasant stimuli60. In addition, studies of healthy children and young adults at high familial risk for depression have yielded evidence that their neural responses to emotional stimuli differed from those of controls at low familial risk for depression93,105.
