PET scans offer insight into how ketamine affects depression
Researchers have developed a new radiotracer that has helped to bring new insight into the effects of depression medication on the brain.
In recent years, ketamine has emerged as a treatment option for individuals with treatment-resistant depression (TRD). Though many patients have reported positive effects with ketamine, very little was known about the underlying biological mechanism that made it more effective than other treatments. Now, thanks to a newly developed radiotracer and PET imaging, experts believe they may have cracked the code on its efficacy.
For the study, researchers targeted the glutamate α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR). AMPAR is known to underlie the process of pharmacological action of ketamine in experimental animals, but has not previously been studied in humans. The group developed a radiotracer, [11C]K-2, to visualize cell-surface AMPAR density in the living human brain on imaging, as prior research has indicated that ketamine’s effect is likely dependent on AMPAR activity.
Researchers compared PET scans conducted using the tracer on a group of patients diagnosed with TRD to those from a healthy control group to determine if there was a correlation between AMPAR density and depression severity. Patients were given either intravenous ketamine or a placebo over a two-week period, while imaging was acquired prior to the start of treatment and once again after the final infusion.
Findings from the PET scans indicated that individuals with TRD had widespread, region-specific abnormalities in AMPAR density compared to healthy controls, but these changes were not uniform across the entire brain. Several cortical regions displayed increases in receptor density in the ketamine group, while decreases in reward-related areas were observed. The observed changes positively correlated with reduced depression symptoms in the ketamine group.
“Ketamine’s antidepressant effect in patients with TRD is mediated by dynamic changes in AMPAR in the living human brain,” explained Professor Takuya Takahashi, MD, PhD, from the Department of Physiology at Yokohama City University Graduate School of Medicine, Japan. “Using a novel PET tracer, [¹¹C]K-2, we were able to visualize how ketamine alters AMPAR distribution across specific brain regions and how these changes correlate with improvements in depressive symptoms.”
The team suggested that their findings could be used to guide treatment decisions pertaining to the use of ketamine in the future.
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In addition to her background in journalism, Hannah also has patient-facing experience in clinical settings, having spent more than 12 years working as a registered rad tech. She began covering the medical imaging industry for Innovate Healthcare in 2021.