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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

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Abstract Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New 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.