In recent years, researchers have discovered that some patients with depression experience significant relief from drugs that affect the brain chemical glutamate. But it remained unclear why some patients responded to these drugs while others did not.
Now researchers from Emory University School of Medicine have discovered which individuals may respond best to these glutamate-targeting drugs: depressed patients with signs of systemic inflammation. The findings show that these patients have elevated levels of glutamate in regions of the brain that are important for motivation.
“Our results suggest that inflammation markers can guide us to which depressed patients respond best to glutamate blockers,” said lead author Ebrahim Haroon, M.D., assistant professor of psychiatry and behavioral sciences at Emory University School of Medicine and Winship Cancer Institute. “This could be an important step toward personalizing treatment for depression.”
Glutamate is an important brain chemical used by neurons to communicate, but at high levels, it can become toxic to both neurons and glia, cells that support brain health. Haroon and team believe that an increase in the levels of glutamate in sensitive regions of the brain may be one of the ways that inflammation may harm the brain and cause depression, possibly through effects on glia.
For the study, the researchers examined 50 patients with depression who were not taking any antidepressant medication. Levels of inflammation were determined by a blood test for C-reactive protein (CRP), which was measured on repeat visits to make sure its levels were stable.
Using an imaging technique called magnetic resonance spectroscopy (MRS), the researchers measured glutamate levels in the basal ganglia, a brain region associated with motor control, motivation and decision-making. The researchers also measured levels of myo-inositol, a marker of glial health.
The findings show that high glutamate and myo-inositol levels in the basal ganglia were directly linked to patients’ reports of anhedonia, the inability to experience pleasure, and slow motor function, as measured by finger tapping speed.
“We focused on the basal ganglia because we had previously seen that a treatment for hepatitis C virus that arouses inflammation and can trigger depressive symptoms could also increase glutamate levels there,” Haroon said.
One such glutamate-targeting drug is the anesthetic drug ketamine. Haroon said the study does not directly explain how ketamine and other similar drugs act against depression, but it does indicate which patients would be likely candidates.
In a similar study of patients with hard-to-treat depression, the researchers found that only those patients with high inflammation markers improved after taking the anti-inflammatory antibody infliximab.
The findings are published in the journal Molecular Psychiatry.
Source: Emory Health Sciences