New research from the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at King’s College London has established a direct connection between increased serotonin release in the frontal cortex and the severity of negative symptoms in individuals with schizophrenia. This groundbreaking study marks a significant step in understanding the neurobiology of schizophrenia, a mental disorder that affects approximately 1 in 100 people globally.
Negative symptoms, which include social withdrawal, lack of motivation, and an overall loss of pleasure in life, are among the most debilitating aspects of schizophrenia. Currently, there are no effective treatments available for these symptoms, making this research particularly timely. The study, titled “Role of Serotonin in the Neurobiology of Schizophrenia and Association with Negative Symptoms,” was published in JAMA Psychiatry in March 2025.
Study Design and Key Findings
For more than six decades, the hypothesis that an overactive serotonin system contributes to schizophrenia symptoms has been discussed, but this study is the first to test this theory in a clinical population. A total of 54 participants were involved, including 26 individuals diagnosed with schizophrenia and 28 healthy control participants. Each participant underwent two positron emission tomography (PET) scans using a radiotracer that specifically binds to serotonin receptors in the brain. Between the scans, they were administered a single dose of d-amphetamine, a drug known to release serotonin.
The analysis revealed that the release of serotonin was significantly greater in the frontal cortex of participants with schizophrenia compared to the control group. This area of the brain is crucial for functions related to motivation and planning. Furthermore, researchers found a strong correlation between increased serotonin release and both the severity of negative symptoms and the level of functional disability experienced by those with schizophrenia.
Expert Perspectives and Future Directions
Dr. Martin Osugo, the lead author of the study, emphasized the profound impact of schizophrenia on individuals’ lives. “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 stated. He highlighted that this study provides the first evidence linking serotonin release to the severity of negative symptoms, suggesting that regulating serotonin levels could pave the way for effective treatments targeting these debilitating aspects of the disorder.
Prof. Oliver Howes, who led the research, echoed this sentiment. He noted that schizophrenia significantly affects motivation and social function, yet little is known about the underlying causes of these symptoms. “Our findings identify a brain system linked to these symptoms that is a promising candidate for treatment,” he said. He underscored the necessity for continued research funding to explore these findings further, expressing hope for future advancements in the treatment of schizophrenia.
The implications of this research could reshape the understanding and management of schizophrenia, particularly concerning its negative symptoms. As scientists continue to investigate the role of serotonin in this complex disorder, there is potential for new therapeutic avenues that could enhance the quality of life for those affected by schizophrenia.
