Researchers have identified a new cluster of preclinical symptoms that may indicate when a young person is at greater risk for developing a psychotic illness, including schizophrenia.
The researchers also identified several biological processes that typically occur during a person’s transition from minor symptoms to clinical psychosis.
Schizophrenia and other types of psychotic illnesses typically begin around 21 years of age, with early warning signs, known as a prodromal syndrome, beginning around age 17, on average. About 30 to 40 percent of young people who meet current criteria for a prodromal syndrome will develop schizophrenia or another psychotic disorder.
“We are moving at an unprecedented pace towards identifying more precise predictors,” said Dr. Elaine Walker, an Emory professor of psychology and neuroscience.
“By increasing our understanding of the factors that give rise to psychosis, we hope to ultimately improve the ability to provide preventive intervention.”
Walker is one of the lead investigators in the North American Prodrome Longitudinal Study (NAPLS). The National Institute of Mental Health (NIMH) funded the continuing study, which unites researchers from Emory, the University of North Carolina, Yale, Harvard, the University of Calgary, University of California, Los Angeles and University of California, San Diego, and the Feinstein Institute at Hillside Hospital in New York.
“The only way we can do this research is by having a large consortium, combining a range of expertise, from genetics to neuroendocrinology, psychology and psychiatry,” Walker said. “It is also difficult to identify individuals who are at risk for psychosis and in order to have enough statistical power, we need a large sample of study subjects.”
The research group has published 60 papers in the last four years, involving more than 800 teens and young adults with prodromal syndrome and a group of 200 healthy youth.
One of the most significant findings was that prodromal youth who had elevated levels of the stress hormone cortisol, as well as signs of neuro-inflammation, were more likely to become psychotic within a year.
“We’ve developed a risk-prediction algorithm, including measures of symptoms as well as biomarkers, that we have made available for clinicians,” Walker said.
“In the future, they can take saliva samples from at-risk patients to check cortisol levels, and to monitor those levels over time.”
“As we get more information, we keep adding to the algorithm to improve the sensitivity and specificity of prediction. It’s important because antipsychotic medications have a lot of side effects. You don’t want to give them to young people unless you are fairly confident that they are on the way to a psychotic disorder.”
The researchers are currently refining a blood-biomarker algorithm that clinicians could use to monitor at-risk patients for signs of neuro-inflammation, oxidative stress, hormones, and metabolism.
“In addition to medication, cognitive therapy and other stress-reducing treatments may help a person safely make it through the high-risk period,” Walker said.
“We’ve found that youth with the highest risk tend to be both exposed to more stress and more reactive to stress,” she said.
The findings also revealed that the brains of at-risk patients who would later develop psychosis showed a dramatic decline of gray matter in the year leading up to the diagnosis. Furthermore, a patient’s cortisol levels directly correlated to the magnitude of decline in brain volume.
“Psychosis is extremely complex, there is no doubt about it, and we’re learning that it’s even more complex than we previously realized,” said Walker. “But if we’re ever going to make progress in prevention and treatment, we’re going to have to come to grips with that complexity and fully understand it.”