New research from the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at King’s College London has identified a significant link between serotonin release in the brain and the severity of negative symptoms in individuals with schizophrenia. This groundbreaking study provides the first direct evidence that an increased release of serotonin in the frontal cortex correlates with debilitating symptoms such as social withdrawal, lack of motivation, and diminished pleasure in life. Currently, these negative symptoms affect approximately 1 in 100 people globally, and existing treatments do not address them effectively.
The findings were published in the journal JAMA Psychiatry in March 2025, establishing a new target for potential treatments aimed at alleviating the challenges faced by those living with schizophrenia.
Study Design and Key Findings
For decades, researchers have suggested that an overactive serotonin system may underlie symptoms of schizophrenia. This current study is the first to test this hypothesis in individuals diagnosed with the disorder. A total of 54 participants were involved, including 26 individuals diagnosed with schizophrenia and 28 healthy controls. Each participant underwent two positron emission tomography (PET) scans, utilizing a radiotracer that selectively binds to serotonin receptors in the brain. Between the scans, participants received a single dose of the serotonin-releasing drug d-amphetamine.
Analysis of the data revealed that the introduction of d-amphetamine caused significant reductions in the binding of the radiotracer in both groups. The main takeaway from this research was that serotonin release was notably higher in the frontal cortex of participants with schizophrenia compared to the control group. Further examination indicated a strong relationship between increased serotonin release and the severity of negative symptoms, as well as the degree of functional disability among those with the disorder.
Expert Perspectives and Future Directions
Dr. Martin Osugo, the study’s lead author, emphasized the profound impact schizophrenia can have 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.” Dr. Osugo noted that the study represents a significant advancement in understanding how serotonin relates to negative symptoms, suggesting that regulating serotonin levels may lead to effective treatments.
Prof. Oliver Howes, who led the research, echoed this sentiment. He remarked, “Schizophrenia often has massive impacts on people’s lives; particularly their motivation and social function. There is little known about what underlies these symptoms and no treatments for this aspect of schizophrenia, so we desperately need new approaches.” He expressed hope that the findings would attract further research funding to explore treatment options targeting the identified serotonin pathway.
This study lays the groundwork for future investigations aimed at developing treatments that could address the crippling negative symptoms of schizophrenia, potentially improving the quality of life for millions affected by this challenging disorder.
