The Crucial Role of Serotonin in the Negative Symptoms of Schizophrenia
30.01.2026
A study conducted by King's College London in collaboration with the University of Padua has provided the first direct evidence that excessive serotonin release in specific areas of the brain is linked to the most debilitating symptoms of schizophrenia. Published in "JAMA Psychiatry" under the title "Role of Serotonin in the Neurobiology of Schizophrenia and Association With Negative Symptoms," the research has identified a potential new therapeutic target for the disease. Mattia Veronese and Lucia Maccioni, both affiliated with the Department of Information Engineering at the University of Padua, participated in the study, which has thus identified a possible new target for the treatment of schizophrenia.
The study, based on a sample of patients, demonstrates that schizophrenia is associated with a significantly higher release of serotonin in the frontal cortex, an area crucial for motivation and planning. This excess is closely correlated with the severity of the so-called "negative symptoms" of the disease, such as social withdrawal, lack of motivation, and loss of pleasure in life.
Researchers analysed 54 individuals (26 with schizophrenia and 28 healthy) by subjecting them to PET scans with a radio-tracer that binds to the brain's serotonin receptors. After a single dose of d-amphetamine, which induces serotonin release, they noticed a much more marked release in the frontal cortex in people with schizophrenia compared to the control group. A direct link was established between this peak, the severity of negative symptoms, and the degree of functional disability. The hypothesis of the involvement of the serotonergic system in schizophrenia had been scientifically proposed over 60 years ago, but an alteration in serotonin release in patients with schizophrenia had never been demonstrated in vivo. Thus, the research results identify...
The team from the University of Padua that participated in the research contributed to measuring the link between the pharmacological action of d-amphetamine and the molecular alterations associated with schizophrenia. "The integration of bioengineering sciences underscores how modern experimental medical research is increasingly multidisciplinary and requires advanced expertise in information technologies and data processing," says Mattia Veronese from the Department of Information Engineering at the University of Padua.
