New research from the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at King’s College London has identified a significant connection between schizophrenia and increased serotonin release in the brain. The study highlights how this neurochemical activity corresponds to the severity of some of the most debilitating symptoms associated with the disorder.
Schizophrenia affects approximately 1 in 100 people worldwide. Among its most challenging symptoms are social withdrawal, lack of motivation, and loss of pleasure in life—collectively referred to as negative symptoms. These aspects of the illness pose substantial barriers to recovery, and currently, no effective treatments exist to address them.
The findings, published in JAMA Psychiatry, establish a foundation for future therapeutic approaches targeting these debilitating symptoms.
Study Design and Key Findings
For over six decades, researchers have suggested that an overactive serotonin system may be linked to schizophrenia symptoms. This study is the first to test that hypothesis directly in individuals diagnosed with the condition.
A total of 54 participants were involved, including 26 individuals with schizophrenia and 28 healthy control participants. Each participant underwent two positron emission tomography (PET) scans using a radiotracer designed to bind selectively to serotonin receptors in the brain. Between the scans, participants were administered a single dose of the serotonin-releasing drug d-amphetamine.
Analysis revealed that the introduction of d-amphetamine produced significant reductions in radiotracer binding in both groups. The most critical finding was that serotonin release was markedly greater in the frontal cortex—a region vital for motivation and planning—among those with schizophrenia compared to healthy controls.
Further analysis indicated a strong relationship between increased serotonin release and both the severity of negative symptoms and the extent of functional impairment in the schizophrenia group.
Expert Perspectives and Future Directions
Dr. Martin Osugo, the study’s first author from King’s IoPPN, emphasized the profound impact of schizophrenia on individuals’ lives. He stated, “The negative symptoms that typify the illness can be extremely isolating and are a huge barrier to people getting back to the activities which are important to them, like hobbies, work, and family life.”
He noted that the study provides vital evidence linking serotonin release with the severity of negative symptoms, representing a significant advancement in understanding the disorder. “If we can successfully regulate serotonin, then it’s possible we might be able to successfully treat negative symptoms,” he added, while underscoring the need for follow-up studies to explore this potential further.
Prof. Oliver Howes, who led the research, highlighted the urgent need for new treatment approaches. He remarked, “There is little known about what underlies these symptoms and no treatments for this aspect of schizophrenia, so we desperately need new approaches.” The findings point to a brain system associated with these debilitating symptoms, providing a hopeful avenue for future research and treatment development.
The study, titled “Role of Serotonin in the Neurobiology of Schizophrenia and Association with Negative Symptoms,” signifies a critical step forward in addressing one of the most challenging aspects of schizophrenia. As researchers seek funding for further studies, the hope is that these insights will lead to effective interventions for those affected by this complex disorder.
For more information, refer to the study published in JAMA Psychiatry in 2025.
