Emory University in Atlanta is playing a key role in the largest, most comprehensive study ever funded by the National Institute of Mental Health (NIMH) of adolescents and young adults at risk for developing a psychotic disorder.
The five-year, $25-million study joins the resources of Emory and seven other major research universities, with the goal of identifying more precise predictors for psychosis, and a better understanding of the neural mechanisms involved.
"This is a critical, watershed study," said Elaine Walker, Samuel Candler Dobbs Professor of Psychology and Neuroscience at Emory. "To date, no one has systematically studied brain development, patterns of electrical brain activity and changes in gene expression in youth at risk for psychosis."
Schizophrenia, the most extreme psychosis, affects about 1 percent of the population and can have devastating consequences. Most people diagnosed with schizophrenia are unable to hold a job or live independently for most of their lives. They often suffer from homelessness, major depression and anxiety disorders.
"Because schizophrenia is severely debilitating, usually chronic and very costly, preventing its onset has become a major area of emphasis of the NIMH," said Walker, who has studied the origins and precursors of psychosis for 30 years.
Early Diagnosis Critical for Teens
The typical onset of schizophrenia and other psychotic disorders is about 21 years of age, with warning signs beginning, on average, around age 17. Studies have shown that about 30 to 40 percent of prodromal teenagers – those showing warning signs – will develop schizophrenia or another psychotic disorder. About 25 percent of the prodromal teens continue to experience mild symptoms without getting worse, while the remaining 35 percent get better as they enter adulthood.
"We are hoping to get to the point where we can identify people who will cross the threshold into psychosis with 85 to 95 percent accuracy, instead of 30 to 40 percent," Walker said. "Evidence has been accumulating that, not only are there brain abnormalities in people with psychotic disorders, the brain abnormalities get worse the longer the patient goes untreated."
While anti-psychotic drugs can be effective, they also have serious side effects, so physicians are hesitant to recommend them until someone enters the clinical stages of psychosis.
Stress Hormones May Hold Key for Treatment
Walker recently completed a study that tracked changes in the stress hormone cortisol over several years in prodromal teenagers. The results found much sharper increases in cortisol levels in the participants who were eventually diagnosed with a psychosis. "This suggests that youth who are vulnerable to psychosis may be especially sensitive to elevations in cortisol selection," Walker said.
One hypothesis of the NIMH study is that changes in stress hormones that occur in at-risk adolescents are influencing gene expression in the brain. "All neurons in the brain have receptors for hormones and research on animals has shown that cortisol can change how these neurons function," Walker said. "If our theory is right, and we can identify what's going on with this process, it's possible that we could eventually modify cortisol secretion in a way that buffers teenagers against its effects, and gets them through this critical risk period."
Each of the eight institutions involved in the NIMH study will recruit 100 prodomal teenagers and 50 controls to participate in the project. Participants will undergo regular diagnostic interviews, measurements of their cortisol levels, magnetic resonance imaging (MRI) to observe physical development of their brains, and electroencephalography (EEG) to measure neural electrical activity. In addition, the researchers will regularly collect and compare genetic data of the participants.
Researchers are now undergoing training in the study protocol, to ensure data standardization. In January, recruitment for participants will begin. In addition to Emory, the institutions involved are: Harvard, Yale, UCLA, UC-San Diego, Einstein Medical College and the University of Calgary.
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