Recent research from the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at King’s College London reveals a significant link between serotonin release in the frontal cortex and the severity of symptoms in individuals with schizophrenia. This study marks the first direct evidence supporting the hypothesis that increased serotonin activity contributes to the disorder, particularly its debilitating negative symptoms, such as social withdrawal and lack of motivation.
Schizophrenia affects approximately 1 in 100 people globally, with negative symptoms often hindering recovery and daily functioning. Currently, there are no effective treatments specifically targeting these symptoms. The findings were published in the March 15, 2025 issue of JAMA Psychiatry, providing a promising foundation for the development of new therapeutic strategies.
Study Design and Key Findings
The hypothesis that an overactive serotonin system might underlie schizophrenia has been suggested for over six decades, yet it had not been empirically tested in individuals diagnosed with the condition until this study. A total of 54 participants took part, including 26 individuals with confirmed schizophrenia and 28 healthy controls. Each participant underwent two positron emission tomography (PET) scans using a radiotracer that binds to serotonin receptors in the brain.
Following the first scan, participants received a single dose of the serotonin-releasing drug d-amphetamine. Analysis revealed that d-amphetamine induced notable reductions in the radiotracer binding across both groups. Crucially, the increase in serotonin release in the frontal cortex was significantly greater in those with schizophrenia. This region of the brain is essential for motivation and planning, underscoring the potential impact of serotonin on these critical functions.
The study further established a correlation between heightened serotonin release and the severity of negative symptoms, as well as the level of functional disability experienced by participants with schizophrenia.
Expert Perspectives and Future Directions
Dr. Martin Osugo, the study’s lead author, emphasized the transformative impact of schizophrenia on individuals’ lives. He remarked, “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 sees the study as an important advancement, suggesting that if serotonin regulation can be effectively achieved, it may pave the way for treatments targeting these challenging symptoms.
Prof. Oliver Howes, who led the research, echoed the urgency for new treatment approaches, stating, “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.” He highlighted the need for further research funding to explore these promising findings.
The study, titled “Role of Serotonin in the Neurobiology of Schizophrenia and Association with Negative Symptoms,” underscores the importance of understanding serotonin’s role in schizophrenia. As researchers continue to explore this pathway, there is renewed hope for developing targeted interventions that could improve the quality of life for those living with this complex mental health condition.
