Approach-Avoidance Conflict in Major Depressive Disorder: Congruent Neural Findings in Humans and Nonhuman Primates
Name
nihms-1539267.pdf
Description
Accepted version
Size
1.37 MB
Format
Adobe PDF
Checksum (MD5)
4e2e1a4c4ee5bb83eb44ab272fe8e078
Author(s)
Ironside, Maria
Amemori, Ken-ichi
McGrath, Callie L.
Pedersen, Mads Lund
Kang, Min Su
Amemori, Satoko
Frank, Michael J.
Graybiel, Ann M
Pizzagalli, Diego A.
Date Issued
March 2020
Journal
Biological Psychiatry
Publisher
Elsevier BV
Citation
Ironside, Maria et al. "Approach-Avoidance Conflict in Major Depressive Disorder: Congruent Neural Findings in Humans and Nonhuman Primates." Biological Psychiatry 87, 5 (March 2020): 339-408 © 2019 Society of Biological Psychiatry
Version
Author's final manuscript
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 nonhuman primate research for use in human functional magnetic resonance imaging (fMRI). Methods: Forty-two female participants, including 18 unmedicated individuals with current MDD (mean age 25.2 ± 5.1 years) and 24 psychiatrically healthy control subjects (mean age 26.3 ± 7.6 years) completed the adapted approach-avoidance task during fMRI. To probe potential mechanistic factors underlying the observed behavioral and fMRI findings and to inform interpretation of putative group differences, we examined electrophysiological data from 2 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 the pregenual cortex, of human subjects and macaques (humans: p <.05 whole-brain corrected; macaques: p <.05). The MDD group exhibited aberrant task-related activations in the anterior cingulate cortex, prefrontal cortex, and striatum (all ps <.05). Neural effects in the MDD group were cross-sectionally associated with stress and depressive symptoms. Importantly, they also prospectively predicted stress at 6-month follow-up (all ps <.05). Conclusions: Findings indicate that there is conservation of anterior cingulate 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.
MIT Department
McGovern Institute for Brain Research at MIT
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/j.biopsych.2019.08.022
