Perioperative Medicine  |   June 2019
Increased Reactivity of the Mesolimbic Reward System after Ketamine Injection in Patients with Treatment-resistant Major Depressive Disorder
Author Notes
  • From the Department of Neuroscience, Faculty of Medicine (V.S., J.H., D.W., A.D., S.S., L.V.), Geneva Neuroscience Center (V.S., J.H., D.W., A.D., S.S., L.V.), and Swiss Center for Affective Sciences (V.S., J.H., D.W., S.S.), University of Geneva, Geneva, Switzerland; Department of Mental Health and Psychiatry, Service of Psychiatric Specialties (S.V., G.M., V.B., A.D., J.-M.A., M.K.), and Department of Anesthesiology, Pharmacology, and Intensive Care (L.V.), University Hospitals of Geneva, Geneva, Switzerland; Faculty of Medicine, University of Namur, Namur, Belgium (M.D.).
  • S.S. and L.V. contributed equally to this article.
    S.S. and L.V. contributed equally to this article.×
  • Submitted for publication December 6, 2017. Accepted for publication January 28, 2019.
    Submitted for publication December 6, 2017. Accepted for publication January 28, 2019.×
  • Address correspondence to Dr. Sterpenich: Department of Neuroscience, University of Geneva Medical School, 9 Chemin des Mines, 1202 Geneva, Switzerland. Virginie.Sterpenich@unige.ch. Information on purchasing reprints may be found at www.anesthesiology.org or on the masthead page at the beginning of this issue. Anesthesiology’s articles are made freely accessible to all readers, for personal use only, 6 months from the cover date of the issue.
Article Information
Perioperative Medicine / Clinical Science / Pharmacology
Perioperative Medicine   |   June 2019
Increased Reactivity of the Mesolimbic Reward System after Ketamine Injection in Patients with Treatment-resistant Major Depressive Disorder
Anesthesiology 6 2019, Vol.130, 923-935. doi:10.1097/ALN.0000000000002667
Anesthesiology 6 2019, Vol.130, 923-935. doi:10.1097/ALN.0000000000002667
Abstract

Editor’s Perspective:

What We Already Know about This Topic:

  • The antidepressant effect of ketamine is associated with increased activity in the reward circuitry of the brain and a suppression of circuitry that mediates perceptual processing of negative emotions. The duration of ketamine effect on these brain structures remains to be defined.

What This Article Tells Us That Is New:

  • 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.

Background: Ketamine rapidly improves maladaptive mood states in major depressive disorder, and some of the neural substrates underlying this therapeutic effect have been identified. This study aimed to identify functional changes within neural networks that may underlie the impact of ketamine on both reward and emotional processing in patients with treatment-resistant major depression.

Methods: Ten adult patients with a Montgomery–Åsberg Depression Rating Scale score above 25 were enrolled to receive a single intravenous administration of ketamine (0.5 mg/kg). Patients’ performance along with related neural network activations were analyzed in a game-like reward task and in an emotional judgment task using functional magnetic resonance imaging 1 day before and 1 and 7 days after ketamine administration.

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.