Research from the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at King’s College London has revealed a significant association between schizophrenia and increased serotonin release in the frontal cortex. This finding provides critical insights into some of the most debilitating symptoms of the disorder, which affects approximately 1 in 100 individuals worldwide. The study emphasizes the need for targeted treatments for negative symptoms, including social withdrawal, lack of motivation, and diminished pleasure in life.
The study titled “Role of Serotonin in the Neurobiology of Schizophrenia and Association with Negative Symptoms” was published in JAMA Psychiatry in March 2025. It highlights that negative symptoms are a major barrier to recovery for those living with schizophrenia, as no effective treatments currently exist for these challenges.
Study Design and Key Findings
For over sixty years, the theory that an overactive serotonin system could contribute to schizophrenia symptoms has been suggested, yet it had never been empirically tested in individuals diagnosed with the disorder. In this study, researchers recruited a total of 54 participants, including 26 individuals with schizophrenia and 28 healthy controls. Participants underwent two positron emission tomography (PET) scans, utilizing a radiotracer that selectively binds to serotonin receptors in the brain.
During the study, participants received a single dose of the serotonin-releasing drug d-amphetamine between the scans. Analysis indicated that the administration of d-amphetamine significantly reduced the binding of the radiotracer in both groups. Crucially, it was found that serotonin release in the frontal cortex, a region essential for motivation and planning, was markedly higher in those with schizophrenia compared to healthy controls.
Further analysis revealed a strong correlation between increased serotonin release, the severity of negative symptoms, and the level of functional disability among participants with schizophrenia. This relationship underscores the potential role of serotonin in these challenging aspects of the disorder.
Expert Insights and Future Directions
Dr. Martin Osugo, the study’s first author, emphasized the profound impact of schizophrenia on individuals’ lives. He noted, “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 expressed optimism about the findings, stating that if serotonin levels can be effectively regulated, it might lead to successful treatment of negative symptoms.
Leading the research, Professor Oliver Howes remarked on the significant effects of schizophrenia on motivation and social function. He stated, “There is little known about what underlies these symptoms and no treatments for this aspect of schizophrenia, so we desperately need new approaches.” He identified the serotonin system as a promising target for future treatments.
This study marks a pivotal step in understanding the neurobiology of schizophrenia and its negative symptoms. Moving forward, researchers will require further funding to explore these findings and develop new treatment strategies aimed at alleviating the burden of negative symptoms for those affected by the disorder.
