Objective: Early life trauma (ELT) is a significant risk factor for the onset of depression. Emerging findings indicate ELT is associated with enhanced amygdala reactivity to aversive stimuli in never-depressed healthy controls as well as those with acute depression but may be absent in non-ELT exposed depressed. The precise mechanism mediating these differences in amygdala reactivity remains unclear. Method: The authors used Granger causality methods to evaluate task-based directional connectivity between medial or lateral prefrontal cortex (PFC) and amygdala in 20 unmedicated patients with current major depressive disorder (MDD) and 19 healthy matched controls while participants engaged in an affective variant of the flanker task comparing response to sad and neutral faces. These data were correlated with childhood trauma history. Results: Exposure to ELT was associated with failure of inhibition within the MDD group based on medial PFC–amygdala connectivity. In contrast, non-ELT exposed MDD was associated with a negative causal pathway from medial prefrontal cortex to amygdala, despite reduced dorsolateral PFC input in comparison to healthy controls. Neither MDD group demonstrated significant lateral PFC–amygdala connectivity in comparison to healthy controls. Conclusions: Failure of the circuit implicated in emotion regulation was associated with a significant history of ELT but not with MDD more broadly. Non-ELT related depression was associated with intact regulation of emotion despite the absence of difference in severity of illness. These findings indicate opposing system-level differences within depression relative to ELT are expressed as differential amygdala reactivity. Hum Brain Mapp 35:4815–4826, 2014. © 2014 Wiley Periodicals, Inc.