Stress-related glutamate changes in the brain and ketamine for loss of pleasure
Official title: Glutamatergic adaptation to stress as a mechanism for anhedonia and treatment response with ketamine
Funded at Emory University · NIH-11248777 · Data updated 2026-11-12
This work looks at whether stress changes a brain chemical called glutamate in people with depression and whether ketamine can help reverse loss of pleasure.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Emory University NIH-funded |
| Lab location | 1 site (Atlanta, United States) |
| Project start | March 1, 2022 |
| Project end | December 31, 2026 |
| Funding year | 2026 |
| Award (this year) | $730,815 |
| NIH project number | 5R01MH126083-05 |
| Project ID | NIH-11248777 on NIH RePORTER |
Who could benefit from this research
✓Could help
Ideal candidates would be adults with major depressive disorder who experience persistent loss of pleasure (anhedonia), and who meet safety criteria for MRI and potential ketamine treatment.
✕Less likely to help
People without depression or anhedonia, those unable to undergo MRI, or those ineligible for ketamine are unlikely to receive direct benefit from this project.
What this research studies
You would have glutamate levels measured in a brain area called the medial prefrontal cortex using MR spectroscopy before and after a short stress challenge, and those measurements would be compared with healthy volunteers. The team will link how glutamate responds to stress with symptoms of loss of pleasure and with expectations about future rewards. For people with depression, the project will examine whether a single ketamine treatment changes glutamate responses and improves motivation. Complementary animal experiments may be used to understand the biological mechanisms behind the human results.
Why it matters
Potential benefit: If successful, this work could point to new ways to target glutamate or use ketamine to reduce anhedonia in people with depression.
How similar studies have gone: Previous clinical and preclinical studies have shown rapid antidepressant and anti-anhedonic effects of ketamine, but linking stress-related glutamate changes measured by MR spectroscopy to treatment response is relatively new.
Where this research is happening
-
Emory University
Atlanta, United States Active
Researchers
- Principal investigator: Treadway, Michael Tilghman — Emory University
- Study coordinator: Treadway, Michael Tilghman
Related research
Other NIH-funded projects on the same topics.
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Synaptic changes behind ketamine’s quick relief of stress-related anhedonia
Researchers are studying how a single low dose of ketamine rapidly eases anhedonia by changing brain connections, aiming to help people with treatment-resistant depression.
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Ketamine's effects on anhedonia and anxiety in depression explored with ultra-high-field brain imaging
Researchers will study how specific brain circuits relate to anhedonia and anxiety in adults with depression using ultra-high-field MRI and ketamine-related insights.
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How stress affects brain chemistry and treatment response in depression
This study is looking at how long-term stress can make people lose interest in things they used to enjoy, which is a common issue for those with depression, and it aims to understand how changes in brain chemicals might explain this, so we can find better treatments for everyone affected.
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How ketamine can quickly reverse stress-related loss of pleasure
This work looks at how a single low dose of ketamine can rapidly restore pleasure and motivation for people with stress-related depression.
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Investigating how ketamine affects depression-related symptoms using advanced MRI technology
This study is looking at how ketamine helps people with depression feel better, especially when it comes to feeling joy and managing anxiety, by using advanced brain scans to see how certain parts of the brain work in adults with depression.
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Investigating how stress affects reward response and treatment with ketamine
This study is looking at how long-term stress can make people with major depressive disorder lose interest in things they used to enjoy, and it aims to understand how a brain chemical called glutamate is involved, especially with the hope that ketamine might help improve these feelings.
About this research
- This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
- Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
- For full project details, budget, and progress reports, visit the official NIH RePORTER page.