Summary: Those with treatment-resistant depression showed significant improvement in symptoms and became more receptive to positive experiences following a one-week ketamine treatment regimen.
Source: Paris Brain Institute
Researchers from Inserm, CNRS, Sorbonne University and clinicians from the AP-HP and at Paris Brain Institute identified one of the mechanisms explaining ketamine effect as an antidepressant.
Ketamine, usually used as an anesthetic, was administered to patients with severe resistant depression. This treatment led patients to present an increased ability to overcome their negative beliefs about themselves and the world when researchers presented them positive information.
These results, published in JAMA Psychiatry, open new therapeutic avenues for the management of antidepressant-resistant mood disorders.
Depression is the most common psychiatric disorder: it is estimated that 5 to 15% of the French population will experience a major depressive episode during their lifetime. All age groups and all social backgrounds are affected.
The disease is characterized by sadness and loss of hedonic feelings that positive events do not improve. Depressed patients progressively develop negative beliefs about themselves, the world, and the future, that may develop into suicidal thoughts. These negative beliefs remain even when the patient receives positive information.
About one-third of people with depression do not respond to the most prescribed antidepressants, leading to a diagnosis of treatment-resistant depression (TRD). For these people, finding new and effective therapies is a priority.
Ketamine, a commonly used anesthetic, has been shown to influence resistant depression. While conventional antidepressant treatments take time to be efficient (on average three weeks), ketamine has a rapid antidepressant effect, only a few hours after administration. The mechanisms associated with this fast-acting antidepressant effect are still unknown.
To identify these mechanisms, Dr. Hugo Bottemanne and the research team co-led at the Paris Brain Institute by Pr Philippe Fossati and Liane Schmidt, Inserm researcher, coordinated a clinical study involving 26 antidepressant-resistant patients (TRD) and 30 healthy controls.
During the protocol, patients and healthy subjects were first asked to estimate the probability of 40 negative events which could occur in their lives (e.g., have a car accident, get cancer, or lose their wallet).
After being informed of the actual occurrence risks in the general population, patients and healthy subjects were again asked to estimate the probability of these events occurring in their lives. The research team was interested in the updating of beliefs after getting information.
Results showed that healthy subjects tended to update their initial beliefs more after receiving factual and positive information, which was not the case in the depressed patient population.
In the suite of the study, TRD patients received three administrations of ketamine at a subanesthetic dose (0.5 mg/kg over 40 minutes) in one week.
Only four hours after the first administration, patients ability to update their beliefs after receiving a positive information was increased. They became less sensitive to negative information and recovered an ability to update their knowledge com parable to that of control subjects.
Moreover, improvement in depressive symptoms after ketamine treatment was associated with these changes in belief updating, suggesting a link between clinical improvement and changes in this cognitive mechanism. In other words, the more patients belief updating ability was increased, the greater the improvement in symptoms was.
In conclusion, in this study, patients with antidepressant-resistant depression showed a significant decrease in symptoms and became more receptive to positive experiences after one week of ketamine treatment.
This work highlights for the first time a cognitive mechanism potentially involved in the early effect of ketamine. It paves the way to new research on antidepressant therapies modulating the mechanisms of belief updating.
Author: Nicolas BrardSource: Paris Brain InstituteContact: Nicolas Brard Paris Brain InstituteImage: The image is in the public domain
Original Research: Open access.Evaluation of Early Ketamine Effects on Belief-Updating Biases in Patients With Treatment-Resistant Depression by Hugo Bottemanne et al. JAMA Psychiatry
Abstract
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 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-sberg 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-sberg 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 grouptesting time pointnews 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: =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 (patha*b: =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.
Read the original post:
Mechanism for the Antidepressant Effect of Ketamine Revealed - Neuroscience News
- Neuroscience Says Music Is an Emotion Regulation Machine. Heres What to Play for Happiness, Productivity, or Deep Thinking - Inc.com - April 19th, 2025 [April 19th, 2025]
- Early Maternal Affection Shapes Key Personality Traits for Life - Neuroscience News - April 19th, 2025 [April 19th, 2025]
- Elons new neuroscience major highlighted by Greensboro News & Record - Elon University - April 19th, 2025 [April 19th, 2025]
- Brain Blast event at St. Lawrence University teaches local students neuroscience - North Country Now - April 19th, 2025 [April 19th, 2025]
- AI Reveals What Keeps People Committed to Exercise - Neuroscience News - April 19th, 2025 [April 19th, 2025]
- The "Holy Grail" of Neuroscience? Researchers Create Stunningly Accurate Digital Twin of the Brain - The Debrief - April 19th, 2025 [April 19th, 2025]
- Annenberg School Vice Dean Emily Falk publishes book on the neuroscience of decision-making - The Daily Pennsylvanian - April 19th, 2025 [April 19th, 2025]
- Music-Induced Chills Trigger Natural Opioids in the Brain - Neuroscience News - April 19th, 2025 [April 19th, 2025]
- What We Value: The Neuroscience of Choice and Change - think.kera.org - April 19th, 2025 [April 19th, 2025]
- Kile takes top neuroscience post at Sutter Health as system pushes to align care, expand trials - The Business Journals - April 19th, 2025 [April 19th, 2025]
- A Grain of Brain, 523 Million Synapses, and the Most Complicated Neuroscience Experiment Ever Attempted - SciTechDaily - April 19th, 2025 [April 19th, 2025]
- Mild Brain Stimulation Alters Decision-Making Speed and Flexibility - Neuroscience News - April 19th, 2025 [April 19th, 2025]
- Cannabis studies were informing fundamental neuroscience in the 1970s - Nature - April 10th, 2025 [April 10th, 2025]
- To make a meaningful contribution to neuroscience, fMRI must break out of its silo - The Transmitter - April 10th, 2025 [April 10th, 2025]
- Steve Jobss Unexpected Secret to Being More Creative (Backed by Neuroscience) - Inc.com - April 10th, 2025 [April 10th, 2025]
- Challenging Decades of Neuroscience: Brain Cells Are More Plastic Than Previously Thought - SciTechDaily - April 10th, 2025 [April 10th, 2025]
- Q&A: Lundbecks head of R&D on letting biology speak in neuroscience - Endpoints News - April 10th, 2025 [April 10th, 2025]
- Why it's hard to study the neuroscience of psychedelics : Short Wave - NPR - April 10th, 2025 [April 10th, 2025]
- Fear Sync: How Males and Females Respond to Stress Together - Neuroscience News - April 10th, 2025 [April 10th, 2025]
- Chemotherapy Disrupts Brain Connectivity - Neuroscience News - April 10th, 2025 [April 10th, 2025]
- Newly awarded NIH grants for neuroscience lag 77 percent behind previous nine-year average - The Transmitter - April 10th, 2025 [April 10th, 2025]
- Wittstein interviewed by The Times News about new neuroscience major - Elon University - April 10th, 2025 [April 10th, 2025]
- Alto Neuroscience initiated with a Buy at H.C. Wainwright - Yahoo Finance - April 10th, 2025 [April 10th, 2025]
- New map of brain hailed as watershed for neuroscience - The Times - April 10th, 2025 [April 10th, 2025]
- GSK Ramps Up Neuroscience Investment With ABL Brain Shuttle Deal - insights.citeline.com - April 10th, 2025 [April 10th, 2025]
- ADHD and Music: Why Background Beats May Boost Study Focus - Neuroscience News - April 10th, 2025 [April 10th, 2025]
- Brains Rewire Themselves to Survive Deadly Infection - Neuroscience News - April 10th, 2025 [April 10th, 2025]
- AbbVie Hold Rating: Balancing Strong Immunology Growth with Challenges in Aesthetics, Neuroscience, and Oncology - TipRanks - April 10th, 2025 [April 10th, 2025]
- Want to Feel Better and Be More Mindful? Neuroscience Says This Habit Might Be Holding You Back - Inc.com - April 10th, 2025 [April 10th, 2025]
- How One Bad Meal Rewires the Brain to Avoid That Food Forever - Neuroscience News - April 10th, 2025 [April 10th, 2025]
- Marcus Neuroscience Institute to Host Brain and Spine Symposium - South Florida Hospital News - March 30th, 2025 [March 30th, 2025]
- Elon University to launch neuroscience major in fall 2025 - Today at Elon - March 30th, 2025 [March 30th, 2025]
- The brains stalwart sentinels express an unexpected gene - The Transmitter: Neuroscience News and Perspectives - March 30th, 2025 [March 30th, 2025]
- Video catches microglia in the act of synaptic pruning - The Transmitter: Neuroscience News and Perspectives - March 30th, 2025 [March 30th, 2025]
- Null and Noteworthy: Reexamining registered reports - The Transmitter: Neuroscience News and Perspectives - March 30th, 2025 [March 30th, 2025]
- Accepting the bitter lesson and embracing the brains complexity - The Transmitter: Neuroscience News and Perspectives - March 30th, 2025 [March 30th, 2025]
- NIH neurodevelopmental assessment system now available as iPad app - The Transmitter: Neuroscience News and Perspectives - March 30th, 2025 [March 30th, 2025]
- Stronger Bonds Before Birth Shape Healthier Mother-Child Futures - Neuroscience News - March 30th, 2025 [March 30th, 2025]
- How Emotionally Intelligent People Learn to Control Their Inner Voice, Backed by Neuroscience - Inc. - March 30th, 2025 [March 30th, 2025]
- Gabriele Scheler reflects on the interplay between language, thought and AI - The Transmitter: Neuroscience News and Perspectives - March 30th, 2025 [March 30th, 2025]
- Worlds first crowd-sourced neuroscience study aims to understand how our brains predict the future - EurekAlert - March 15th, 2025 [March 15th, 2025]
- Rewriting Neuroscience: Possible Foundations of Human Intelligence Observed for the First Time - SciTechDaily - March 15th, 2025 [March 15th, 2025]
- Calculating neurosciences carbon cost: Q&A with Stefan Pulver and William Smith - The Transmitter: Neuroscience News and Perspectives - March 15th, 2025 [March 15th, 2025]
- The future of neuroscience research at U.S. minority-serving institutions is in danger - The Transmitter: Neuroscience News and Perspectives - March 15th, 2025 [March 15th, 2025]
- Dopamine and social media: Why you cant stop scrolling, according to neuroscience - PsyPost - March 15th, 2025 [March 15th, 2025]
- Neuroscience Discovered a Clever Trick for Squeezing More Joy Out of Everyday Pleasures - Inc. - March 15th, 2025 [March 15th, 2025]
- The limits of neuroscience - The Transmitter: Neuroscience News and Perspectives - March 15th, 2025 [March 15th, 2025]
- BPOM Explains The Benefits Of Fasting From The Health And Neuroscience Side - VOI English - March 15th, 2025 [March 15th, 2025]
- How tiny tardigrades could help tackle systems neuroscience questions - The Transmitter: Neuroscience News and Perspectives - March 15th, 2025 [March 15th, 2025]
- Alison Preston explains how our brains form mental frameworks for interpreting the world - The Transmitter: Neuroscience News and Perspectives - March 15th, 2025 [March 15th, 2025]
- The Mystical Mind Meets Neuroscience: Seeking the Roots of Consciousness - Next Big Idea Club Magazine - March 15th, 2025 [March 15th, 2025]
- Myosin Therapeutics Closes Second Seed Round to Advance Clinical Trials for Innovative Cancer and Neuroscience Therapies - PR Newswire - March 5th, 2025 [March 5th, 2025]
- Neuroscience Ph.D. programs adjust admissions in response to U.S. funding uncertainty - The Transmitter: Neuroscience News and Perspectives - March 5th, 2025 [March 5th, 2025]
- New tools help make neuroimaging accessible to more researchers - The Transmitter: Neuroscience News and Perspectives - March 5th, 2025 [March 5th, 2025]
- Future Thinking Training Reduces Impulsivity - Neuroscience News - March 5th, 2025 [March 5th, 2025]
- Null and Noteworthy, relaunched: Probing a schizophrenia biomarker - The Transmitter: Neuroscience News and Perspectives - March 5th, 2025 [March 5th, 2025]
- How to communicate the value of curiosity-driven research - The Transmitter: Neuroscience News and Perspectives - March 5th, 2025 [March 5th, 2025]
- Cognitive neuroscience approach to explore the impact of wind turbine noise on various mental functions - Nature.com - March 5th, 2025 [March 5th, 2025]
- Football on the Brain: Helping coaches embed neuroscience knowledge - Training Ground Guru - March 5th, 2025 [March 5th, 2025]
- Taking Control: Using Neuroscience to Build Better Lives - theLoop - March 5th, 2025 [March 5th, 2025]
- Creating a pipeline of talent to feed the growth of Neuroscience: Lessons from Ghana - Myjoyonline - March 5th, 2025 [March 5th, 2025]
- Exclusive: NIH appears to archive policy requiring female animals in studies - The Transmitter: Neuroscience News and Perspectives - February 25th, 2025 [February 25th, 2025]
- Roll On Down The Highway 2025 Tour coming to Neuroscience Group Field - WeAreGreenBay.com - February 25th, 2025 [February 25th, 2025]
- STEM organizations host Neuroscience Outreach Fair for local K-12 students - University of Virginia The Cavalier Daily - February 25th, 2025 [February 25th, 2025]
- Adapt or die: Safeguarding the future of diversity and inclusion funding in neuroscience - The Transmitter: Neuroscience News and Perspectives - February 25th, 2025 [February 25th, 2025]
- The last two-author neuroscience paper? - The Transmitter: Neuroscience News and Perspectives - February 25th, 2025 [February 25th, 2025]
- Gate Neurosciences Strengthens Focus on the Synapse as a Therapeutic Target with Acquisition of Boost Neuroscience - Business Wire - February 25th, 2025 [February 25th, 2025]
- Why Firefly Neuroscience, Inc. (AIFF) Is Soaring This Year So Far - Yahoo Finance - February 25th, 2025 [February 25th, 2025]
- Breaking the barrier between theorists and experimentalists - The Transmitter: Neuroscience News and Perspectives - February 25th, 2025 [February 25th, 2025]
- Preserving Brain Health and Advancing Neuroscience - University of Miami - February 25th, 2025 [February 25th, 2025]
- Science must step away from nationally managed infrastructure - The Transmitter: Neuroscience News and Perspectives - February 25th, 2025 [February 25th, 2025]
- Repurposed Blood Pressure Drug May Treat ADHD - Neuroscience News - February 25th, 2025 [February 25th, 2025]
- How to teach students about science funding - The Transmitter: Neuroscience News and Perspectives - February 25th, 2025 [February 25th, 2025]
- Reflecting on 2024: Advancing Neuroscience Research to Improve Neurological Health - National Institute of Neurological Disorders and Stroke - February 25th, 2025 [February 25th, 2025]
- Brains Hidden Circuitry for Risk and Reward Uncovered - Neuroscience News - February 25th, 2025 [February 25th, 2025]
- Why We Keep Exploring Even After Learning the Best Strategy - Neuroscience News - February 25th, 2025 [February 25th, 2025]
- Unlocking Cellular Youth: The Protein That Reverses Aging - Neuroscience News - February 25th, 2025 [February 25th, 2025]
- This paper changed my Life: Bill Newsome reflects on a quadrilogy of classic visual perception studies - The Transmitter: Neuroscience News and... - February 25th, 2025 [February 25th, 2025]
- Roundup: The false association between vaccines and autism - The Transmitter: Neuroscience News and Perspectives - February 3rd, 2025 [February 3rd, 2025]
- Static pay, shrinking prospects fuel neuroscience postdoc decline - The Transmitter: Neuroscience News and Perspectives - February 3rd, 2025 [February 3rd, 2025]