Increased Reactivity of the Mesolimbic Reward System after Ketamine Injection in Patients with Treatment-resistant Major Depressive Disorder

Virginie Sterpenich, Sonia Vidal, Jeremy Hofmeister, Giorgio Michalopoulos, Victor Bancila, Delphine Warrot, Alexandre Dayer, Martin Desseilles, Jean Michel Aubry, Markus Kosel, Sophie Schwartz, Laszlo Vutskits

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)923-935
Number of pages13
JournalAnesthesiology
Volume130
Issue number6
DOIs
Publication statusPublished - 1 Jun 2019

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Treatment-Resistant Depressive Disorder
Major Depressive Disorder
Ketamine
Reward
Injections
Ventral Tegmental Area
Prefrontal Cortex
Brain
Amygdala
Depression
Gyrus Cinguli
Therapeutic Uses
Intravenous Administration
Antidepressive Agents
Reaction Time

Cite this

Sterpenich, V., Vidal, S., Hofmeister, J., Michalopoulos, G., Bancila, V., Warrot, D., ... 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. https://doi.org/10.1097/ALN.0000000000002667
Sterpenich, Virginie ; Vidal, Sonia ; Hofmeister, Jeremy ; Michalopoulos, Giorgio ; Bancila, Victor ; Warrot, Delphine ; Dayer, Alexandre ; Desseilles, Martin ; Aubry, Jean Michel ; Kosel, Markus ; Schwartz, Sophie ; Vutskits, Laszlo. / Increased Reactivity of the Mesolimbic Reward System after Ketamine Injection in Patients with Treatment-resistant Major Depressive Disorder. In: Anesthesiology. 2019 ; Vol. 130, No. 6. pp. 923-935.
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Sterpenich, V, Vidal, S, Hofmeister, J, Michalopoulos, G, Bancila, V, Warrot, D, Dayer, A, Desseilles, M, Aubry, JM, 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, vol. 130, no. 6, pp. 923-935. https://doi.org/10.1097/ALN.0000000000002667

Increased Reactivity of the Mesolimbic Reward System after Ketamine Injection in Patients with Treatment-resistant Major Depressive Disorder. / Sterpenich, Virginie; Vidal, Sonia; Hofmeister, Jeremy; Michalopoulos, Giorgio; Bancila, Victor; Warrot, Delphine; Dayer, Alexandre; Desseilles, Martin; Aubry, Jean Michel; Kosel, Markus; Schwartz, Sophie; Vutskits, Laszlo.

In: Anesthesiology, Vol. 130, No. 6, 01.06.2019, p. 923-935.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Increased Reactivity of the Mesolimbic Reward System after Ketamine Injection in Patients with Treatment-resistant Major Depressive Disorder

AU - Sterpenich, Virginie

AU - Vidal, Sonia

AU - Hofmeister, Jeremy

AU - Michalopoulos, Giorgio

AU - Bancila, Victor

AU - Warrot, Delphine

AU - Dayer, Alexandre

AU - Desseilles, Martin

AU - Aubry, Jean Michel

AU - Kosel, Markus

AU - Schwartz, Sophie

AU - Vutskits, Laszlo

PY - 2019/6/1

Y1 - 2019/6/1

N2 - 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.

AB - 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.

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