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Evaluation of Early Ketamine Effects on Belief-Updating Biases in Patients With Treatment-Resistant Depression

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...

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Autores principales: Bottemanne, Hugo, Morlaas, Orphee, Claret, Anne, Sharot, Tali, Fossati, Philippe, Schmidt, Liane
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Medical Association 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9520441/
https://www.ncbi.nlm.nih.gov/pubmed/36169969
http://dx.doi.org/10.1001/jamapsychiatry.2022.2996
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author Bottemanne, Hugo
Morlaas, Orphee
Claret, Anne
Sharot, Tali
Fossati, Philippe
Schmidt, Liane
author_facet Bottemanne, Hugo
Morlaas, Orphee
Claret, Anne
Sharot, Tali
Fossati, Philippe
Schmidt, Liane
author_sort Bottemanne, Hugo
collection PubMed
description 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: This study used an observational case-control protocol with a mixed-effects design that nested 2 groups by 2 testing time points. Observers were not blinded. Patients with treatment-resistant depression (TRD) and healthy volunteer participants aged 34 to 68 years were included. Patients with TRD were diagnosed with major depressive disorder or bipolar depression, had a Montgomery-Åsberg Depression Rating Scale score greater than 20, a Maudsley Staging Method score greater than 7, and failed to respond to at least 2 prior antidepressant trials. Exclusion criteria were any other psychiatric, neurological, or neurosurgical comorbidities, substance use or addictive disorders, and recreational ketamine consumption. Data were collected from January to February 2019 and from May to December 2019, and data were analyzed from January 2020 to July 2021. 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; t(216) = −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], t(25) = 3.8; P < .001) and partially mediated early antidepressant responses (path a*b: β = −1.00 [SEM, 0.66]; t(26) = −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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spelling pubmed-95204412022-10-18 Evaluation of Early Ketamine Effects on Belief-Updating Biases in Patients With Treatment-Resistant Depression Bottemanne, Hugo Morlaas, Orphee Claret, Anne Sharot, Tali Fossati, Philippe Schmidt, Liane JAMA Psychiatry Original Investigation 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: This study used an observational case-control protocol with a mixed-effects design that nested 2 groups by 2 testing time points. Observers were not blinded. Patients with treatment-resistant depression (TRD) and healthy volunteer participants aged 34 to 68 years were included. Patients with TRD were diagnosed with major depressive disorder or bipolar depression, had a Montgomery-Åsberg Depression Rating Scale score greater than 20, a Maudsley Staging Method score greater than 7, and failed to respond to at least 2 prior antidepressant trials. Exclusion criteria were any other psychiatric, neurological, or neurosurgical comorbidities, substance use or addictive disorders, and recreational ketamine consumption. Data were collected from January to February 2019 and from May to December 2019, and data were analyzed from January 2020 to July 2021. 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; t(216) = −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], t(25) = 3.8; P < .001) and partially mediated early antidepressant responses (path a*b: β = −1.00 [SEM, 0.66]; t(26) = −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. American Medical Association 2022-09-28 2022-11 /pmc/articles/PMC9520441/ /pubmed/36169969 http://dx.doi.org/10.1001/jamapsychiatry.2022.2996 Text en Copyright 2022 Bottemanne H et al. JAMA Psychiatry. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the CC-BY License.
spellingShingle Original Investigation
Bottemanne, Hugo
Morlaas, Orphee
Claret, Anne
Sharot, Tali
Fossati, Philippe
Schmidt, Liane
Evaluation of Early Ketamine Effects on Belief-Updating Biases in Patients With Treatment-Resistant Depression
title Evaluation of Early Ketamine Effects on Belief-Updating Biases in Patients With Treatment-Resistant Depression
title_full Evaluation of Early Ketamine Effects on Belief-Updating Biases in Patients With Treatment-Resistant Depression
title_fullStr Evaluation of Early Ketamine Effects on Belief-Updating Biases in Patients With Treatment-Resistant Depression
title_full_unstemmed Evaluation of Early Ketamine Effects on Belief-Updating Biases in Patients With Treatment-Resistant Depression
title_short Evaluation of Early Ketamine Effects on Belief-Updating Biases in Patients With Treatment-Resistant Depression
title_sort evaluation of early ketamine effects on belief-updating biases in patients with treatment-resistant depression
topic Original Investigation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9520441/
https://www.ncbi.nlm.nih.gov/pubmed/36169969
http://dx.doi.org/10.1001/jamapsychiatry.2022.2996
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