Clinical studies have demonstrated both the fast antidepressant effects of subanesthetic ketamine infusions and the maintenance of depression by persistently unfavorable attitudes. For a study, researchers sought to assess if ketamine affects belief updating and how these cognitive changes related to ketamine’s therapeutic benefits.

In the study, 2 groups were tested at 2 different time periods using a mixed-effects observational case-control technique. The observers weren’t made blind. Patients with treatment-resistant depression (TRD) and healthy volunteers were both included. Participants ages ranged from 34 to 68. Major depressive disorder or bipolar depression diagnosis, a Maudsley Staging Method score of at least 7, a Montgomery-Åsberg Depression Rating Scale score of at least 20, and failure to react to at least two prior antidepressant treatments were also requirements for patients with TRD. Any further mental, neurological, or neurosurgical conditions, addictions to drugs or alcohol, and recreational ketamine usage were prohibited. Data were gathered between January and February 2019 and May through December 2019, and data analysis took place between January 2020 and July 2021. Patients with TRD were monitored for 24 hours before a single infusion of ketamine, 4 hours following the infusion, and 4 hours following the third dose, administered 1 week after the initial infusion. Participants in the healthy control group had two 1-week-apart observations. Montgomery-Åsberg Depression When patients got both good and negative news, the Rating Scale score and belief updating were evaluated using a cognitive belief-updating task and mathematically formalized using a computational reinforcement learning model. 

The mean (SEM) age of the 56 participants that were included was 52.3 (1.2) years, and 29 (52%) of them were male. There were 30 individuals in the control group and 26 patients with TRD altogether. Following a single ketamine infusion, patients with TRD updated their beliefs more frequently than controls after receiving good news as opposed to bad news, according to a significant group × testing time point × and news valence interaction (controlled for age and education: β = −0.91; 95% CI, −1.58 to −0.24; t216 = −2.67; P = .008). Asymmetrical learning rates (LRs) after ketamine treatment were linked to this effect, according to computational modeling (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).

The findings offered fresh understandings of the cognitive mechanisms underlying ketamine’s therapeutic effects in patients with TRD and offered bright prospects for augmented psychotherapy for people suffering from mood disorders.