Surge in serotonin points to new treatment target for schizophrenia

New research from the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at King’s College London has provided the first direct evidence that schizophrenia is associated with a greater release of serotonin in the frontal cortex, and demonstrates its link to a greater severity of some of the most disabling symptoms of the disorder.

Schizophrenia is a mental disorder that affects about 1 in 100 people in the world. Some of the most disabling symptoms are social withdrawal, lack of motivation and loss of pleasure in life. These are called negative symptoms, and are a major factor in people not being able to recover from the illness and getting on with their lives. There is no current treatment for them.

The study, “Role of Serotonin in the Neurobiology of Schizophrenia and Association with Negative Symptoms” was recently published in JAMA Psychiatry and provides a basis for future treatments designed to target these highly disabling symptoms in schizophrenia.

Study design and key findings

The idea that an overactive serotonin system underlies schizophrenia symptoms has been proposed for more than 60 years, but it had never previously been tested in people living with schizophrenia.

A total of 54 people—26 with a confirmed diagnosis of schizophrenia and 28 healthy control participants—were recruited for this study. All participants underwent two PET scans with a radiotracer that selectively binds to brain serotonin receptors. Between the two scans, they received a single dose of the serotonin releasing drug d-amphetamine.

An analysis of the data found that the introduction of d-amphetamine led to substantial reductions in binding of the radiotracer in both those with schizophrenia and healthy volunteers. The main finding of the study was that this release of serotonin was significantly greater in parts of the brain that are key to motivation and planning (the frontal cortex) in people with schizophrenia compared to controls.

Further analysis established a close relationship between greater serotonin release and both the severity of negative symptoms and the degree of functional disability in the schizophrenia group.

Expert perspectives and future directions

Dr. Martin Osugo, the study’s first author from King’s IoPPN said, “Schizophrenia is a life-altering condition that can have a dramatic impact on a person’s well-being. 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.

“Our study, which provides the first evidence that serotonin release is associated with the severity of negative symptoms, is an important step forward in this field. If we can successfully regulate serotonin, then it’s possible we might be able to successfully treat negative symptoms.

“This is only the first step, however, and we need to conduct follow-up studies to test this.”

Prof Oliver Howes, who led the research, said, “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. Our findings identify a brain system linked to these symptoms that is a promising candidate for treatment. This gives us hope for the future, but we will need further research funding to develop this.”