Morris, L. S., Costi, S., Tan, A., Stern, E. R., Charney, D. S., & Murrough, J. W. (2020). Ketamine normalizes subgenual cingulate cortex hyper-activity in depression. Neuropsychopharmacology, 45(6), 975–981.
- There was a significant improvement in MDD symptoms following a single-dose intravenous ketamine.
- Following a 40-minute infusion of ketamine at a dose of 0.5mg/kg, patients with major depressive disorder showed positive changes to their subgenual anterior cingulate cortex using functional MRI to scan the brain.
- These findings suggest a neural mechanism by which ketamine exerts its antidepressant efficacy, via rapid blunting of aberrant sgACC hyper-reactivity to positive incentives.
These data are consistent with previous studies in animal models demonstrating excessive stress-related glutamatergic signaling in projections from the hippocampus to sgACC, sgACC hyperactivity, and links with anhedonic behaviors. We demonstrate a double dissociation whereby sgACC hyper-activation to positive feedback is associated with anhedonia, whereas hyper-activation to negative feedback is associated with anxiety. In addition, we show that ketamine blunts sgACC hyper-activation to positive feedback, but not negative feedback in patients with MDD. Finally, we highlight a potential anatomical distinction within sgACC, whereby posterior area 25 is more related to positive processing and anhedonia, whereas anterior PL32 is more associated with negative processing and anxiety.