Bottemanne, Hugo;
Morlaas, Orphee;
Claret, Anne;
Sharot, Tali;
Fossati, Philippe;
Schmidt, Liane;
(2022)
Evaluation of Early Ketamine Effects on Belief-Updating Biases in Patients With Treatment-Resistant Depression.
JAMA Psychiatry
, 79
(11)
pp. 1124-1132.
10.1001/jamapsychiatry.2022.2996.
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Abstract
IMPORTANCE: Clinical research has shown that persistent negative beliefs maintain depression and that subanesthetic ketamine infusions induce rapid antidepressant responses. OBJECTIVE: To evaluate whether ketamine alters belief updating and how such cognitive effects are associated with the clinical effects of ketamine. DESIGN, SETTING, AND PARTICIPANTS: To evaluate whether ketamine alters belief updating and how such cognitive effects are associated with the clinical effects of ketamine. EXPOSURES: Patients with TRD were observed 24 hours before single ketamine infusion, 4 hours after the infusion, and 4 hours after the third infusion, which was 1 week after the first infusion. Healthy control participants were observed twice 1 week apart without ketamine exposure. MAIN OUTCOMES AND MEASURES: Montgomery-Åsberg Depression Rating Scale score and belief updating after belief updating when patients received good news and bad news measured by a cognitive belief-updating task and mathematically formalized by a computational reinforcement learning model. RESULTS: Of 56 included participants, 29 (52%) were male, and the mean (SEM) age was 52.3 (1.2) years. A total of 26 patients with TRD and 30 control participants were included. A significant group × testing time point × news valence interaction showed that patients with TRD updated their beliefs more after good than bad news following a single ketamine infusion (controlled for age and education: β = −0.91; 95% CI, −1.58 to −0.24; t216 = −2.67; P = .008) than controls. Computational modeling showed that this effect was associated with asymmetrical learning rates (LRs) after ketamine treatment (good news LRs after ketamine, 0.51 [SEM, 0.04]; bad news LRs after ketamine 0.36 [SEM, 0.03], t25 = 3.8; P < .001) and partially mediated early antidepressant responses (path a*b: β = −1.00 [SEM, 0.66]; t26 = −1.53; z = −1.98; P = .04). CONCLUSIONS AND RELEVANCE: These findings provide novel insights into the cognitive mechanisms of the action of ketamine in patients with TRD, with promising perspectives for augmented psychotherapy for individuals with mood disorders.
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