Approach-avoidance conflict in major depression: Congruent neural findings in human and non-human primates

Abstract Background Maladaptive approach-avoidance behavior has been implicated in the pathophysiology of major depressive disorder (MDD), but the neural basis of these abnormalities in decision-making remains unclear. Capitalizing on recent preclinical findings, we adapted an approach-avoidance conflict task from non-human primate research for use in human functional MRI. Methods Forty-two female participants, including 18 unmedicated individuals with current MDD (mean age 25.2 ± 5.1) and 24 psychiatrically healthy controls (mean age 26.3 ± 7.6) completed the adapted approach-avoidance task during functional MRI. To probe potential mechanistic factors underlying the observed behavioral and fMRI findings and inform interpretation of putative group differences, we examined electrophysiological data from two female Macaca mulatta monkeys performing the approach-avoidance conflict task mimicked in the fMRI study. Results Findings demonstrated congruent neural correlates of approach-avoidance conflict and aversive responsiveness in the anterior cingulate cortex, including pregenual cortex, of human subjects and macaques (humans p Conclusions Findings indicate there is conservation of anterior cingulate regions of activation across species and that frontal and striatal regions, in unmedicated humans with MDD, are abnormally responsive during cost-benefit decision-making. We suggest that these disruptions could be valuable candidates for translational biomarkers.