Sterpenich, V., Vidal, S., Hofmeister, J., Michalopoulos, G., Bancila, V., Warrot, D., Dayer, A., Desseilles, M., Aubry, J.-M., Kosel, M., Schwartz, S., & Vutskits, L. (2019). Increased reactivity of the mesolimbic reward system after ketamine injection in patients with treatment-resistant major depressive disorder. Anesthesiology, 130(6), 923–935.
Highlights:
- As expected, ketamine administration led to an improvement in mood and global vigilance. The improvement in mood was accompanied by an increased recruitment of the orbitofrontal cortex, ventral striatum, medial substantial nigra and ventral tegmental area, structures that are part of the reward circuitry.
- Responses in the mesolimbic structures (amygdala, medial substantial nigra and ventral tegmental area, orbitofrontal cortex) to negative stimuli were decreased after ketamine administration.
- The data are consistent with the premise that ketamine induces sustained changes in the mesolimbic neural circuits to reset pathological reward and emotional processing.
Results:
A significant correlation (R2 = 0.46, P = 0.03) between the improvement of depression scores and the enhanced reaction time for positive items was found in the game-like reward task 1 day after ketamine administration. This enhanced sensitivity for rewarded items was accompanied by increased activity of reward-related brain regions, including the orbitofrontal cortex, ventral striatum, and the ventral tegmental area, an effect that persisted up to 1 week after ketamine injection. In the emotional judgment task, it was found that ketamine rapidly modified local brain activities in response to emotionally negative, positive, or neutral stimuli in the amygdala, insula, anterior cingulate cortex, and in the ventral tegmental area.
Conclusions:
Single bolus ketamine administration rapidly triggers lasting changes in mesolimbic neural networks to improve pathologic reward and emotional processing in patients with major depressive disorder.
