New Insights into Serotonin Release in Depression Based on Direct Brain Imaging
Researchers from Invicro and Imperial College London have obtained direct evidence that the release of serotonin is reduced in the brains of individuals with depression, lending support to the serotonin hypothesis of depression. The findings were published in Biological Psychiatry and add a new layer of data to the ongoing discussion about neurotransmitter involvement in mood disorders.
Since the 1960s, scientists have entertained the idea that major depressive disorder arises from disruptions in the serotonin transmission system. While much of the early evidence was indirect, it was plentiful. A recent comprehensive review, however, concluded that there is limited strong evidence in favor of the serotonin hypothesis. Despite this uncertainty, most antidepressant medications continue to aim at raising extracellular serotonin, also known as 5 hydroxytryptamine or 5-HT, in an effort to lift mood and improve symptoms.
The latest study employed an innovative imaging technique designed to measure serotonin released from neurons in response to pharmacological challenges. The team compared serotonin release in 17 individuals diagnosed with depression against 20 healthy controls, treating the groups under similar experimental conditions to reduce confounding factors.
Results from the imaging scans showed that serotonin release was diminished in several critical regions of the brain among participants with depression. Importantly, the researchers found no clear link between how severe the depressive symptoms were and the degree of serotonin release deficiency, suggesting that reduced serotonin release may be a characteristic feature of the condition rather than a direct result of symptom severity.
The authors stressed that the reduced serotonin releasing capacity appears to be a marker of depression rather than a consequence of antidepressant treatment, noting that a substantial portion of the depressed participants had never used antidepressants. This distinction helps clarify the direction of causality in serotonin-related changes observed in depression.
While the impairment in serotonin transmission cannot account for every symptom or the full range of depressive subtypes, the finding demonstrates that serotonin deficiency exists in individuals with depression who have not taken medication. The work provides a more direct link between brain chemistry and depressive states, contributing to a broader understanding of how serotonin systems may influence mood and behavior across diverse patient groups. The study is available with attribution to the Biological Psychiatry report and is part of a growing body of research examining neurotransmitter dynamics in mental health. [Biological Psychiatry study attribution]