Study Results Show Direct Evidence of Serotonin Disruption Linked With Depression

Article

First direct evidence of diminished 5-HT release proves hypothesis, according to a new analysis published in Biological Psychiatry.

New study results published in Biological Psychiatry showed direct evidence of disrupted serotonin release in the brain links with depression.

“Our thinking about the role of serotonin in depression has evolved significantly over the past decade. We once thought that serotonin changes could account for the entirety of depression,” John Krystal, MD, editor-in-chief of Biological Psychiatry, said in a statement.

“When this simple hypothesis could no longer be supported, some were inclined to dismiss any role for serotonin in depression,” he said.

“The current study provides important new support for further exploration of the role of serotonin in depression. This is particularly timely, as drugs targeting serotonin receptors, such as psychedelics, are being explored as potential new treatments for mood disorders,” Krystal said.

Investigators from Copenhagen University, Imperial College London, King’s College London, and the University of Oxford used a novel imaging technique to study the magnitude of serotonin released from neurons in response to pharmacological challenges.

The same group of investigators used positron emission tomography with the radioligand [11C]Cimbi-36 to detect serotonin release in their previous work.

In this study, investigators applied the same method to compare serotonin release in 17 individuals with depression and 20 individuals without depression.

“This study used a new and more direct method to measure serotonin in the living human brain, and the results suggest reduced serotonin [release] functioning in depression. This imaging method, in combination with similar methods for other brain systems, has the potential to help us to better understand the varying, sometimes limited or even lacking, treatment responses that people with depression have to antidepressant medication,” David Erritzoe, MRCPsych, PhD, lead author of the study, said in the statement.

Both groups of individuals underwent positron emission tomography scanning with [11C]Cimbi-36 to measure 5-HT2A receptor availability in the frontal cortex. The groups did not differ significantly at baseline.

Investigators gave both groups a dose of d-amphetamine, a stimulant drug that works to increase 5-HT concentration outside of neurons, where it interacts with 5-HT2A receptors and reduces the binding of [11C]Cimbi-36.

Three hours after drug administration, investigators performed a second scan, which showed that healthy control individuals had significantly reduced 5-HT2A receptor availability, indicating an increase in serotonin levels.

However, the individuals with depression did not show a significant decrease in binding potential, which indicated a blunted serotonin release capacity in key brain regions.

The results showed that there was no relationship between the severity of depression and the extent of serotonin release capacity deficits.

Furthermore, all individuals in the study were not under the influence of antidepressant medication, and 11 of 17 had never received antidepressant treatment, investigators said.

This proves that the low serotonin release capacity is a feature of depression, not antidepressant treatment, investigators said.

Investigators confirmed that the study demonstrates that serotonergic deficits are present in unmedicated individuals with depression. However, they think that serotonergic dysfunction is unlikely the explanation for the clinical features of depression.

Reference

New support for a serotonin deficit in depression. EurekAlert. News release. December 15, 2022. Accessed December 21, 2022. https://www.eurekalert.org/news-releases/974582

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