Psychosis, a mental condition, is characterized by a break from reality during which an individual may experience delusions and hallucinations. While schizophrenia is best known for episodes of psychosis, it is also marked by chronic neurocognitive deficits,
such as problems with memory and attention.
A multi-site cognition study
led by psychologists at Beth Israel Deaconess Medical Center (BIDMC)
found that these neurocognitive symptoms are evident prior to the onset
of psychosis in a high-risk stage of the disorder called the prodromal
‘While schizophrenia is best known for episodes of psychosis, it is also marked by chronic neurocognitive deficits, such as problems with memory and attention.’
Published today online in advance of print in JAMA Psychiatry
the findings suggest that these impairments may serve as early warning
signs of schizophrenia, as well as potential targets for intervention
that could mitigate the onset of the psychotic disorder and
significantly improve cognitive function.
"To our knowledge, this is the largest and most definitive study of
cognition in the high-risk period before onset of for
psychosis/schizophrenia," said corresponding author Larry J. Seidman,
a psychologist at BIDMC and professor of psychology at Harvard
Medical School. "This is part of a paradigm shift in the way we are
focusing on the earlier, prodromal phase of the disorder in an effort to
identify those most likely to develop psychosis."
Seidman and colleagues collected neurocognitive functioning data
from participants at eight university-based, outpatient programs in the
United States and Canada over the course of four years. The
observational study compared 689 males and females deemed at clinical
high risk (CHR) of developing psychosis to 264 male and female healthy
Using 19 standard tests of executive and visuospatial
abilities, attention and working memory, verbal abilities and
declarative memory, the researchers found that the high-risk group
performed significantly worse than the control group on all 19 measures.
Among the high-risk individuals only, those who later progressed to a
psychotic disorder performed significantly worse than their high-risk
peers who did not develop psychosis during the study.
"Currently, when mental health professionals assess people coming in
for evaluation, we don't know who will eventually develop
schizophrenia," said Seidman. "Our group's focus is on identifying early
warning signs and then developing interventions to improve a person's
chances for not getting it, making it milder or delaying it."
Impaired working memory (the ability to hold information like a
phone number in mind for a short time while it's in use) and declarative
memory (the ability to recall things learned in the last few minutes)
turned out to be the key neurocognitive functions that are impaired in
the high-risk, prodromal phase prior to the onset of full-blown
psychosis. These findings, said Seidman, are in keeping with the
experiences of many people with schizophrenia who report sudden
difficulties reading, concentrating or remembering things in the
earliest days of the disorder.
Schizophrenia "conjures up dread" in our culture, Seidman said, but
he notes that it is likely these cognitive deficits - not the delusions
and hallucinations people fear so much - that keep roughly 80 percent of
people with schizophrenia out of work or school. Recent focus on the
prodromal period and the growing promise of early intervention is giving
patients and their families more realistic hope that better outcomes
are possible, he added.
"People can hear voices and still function pretty well, but they
basically cannot function at all when their cognition is impaired," he
said. "We are also testing a number of cognitive remediation and
enhancement treatments to determine their role in the evolution of the
illness. There's more evidence suggesting that early intervention
reduces the number of people who transition to schizophrenia."
This study represented the second phase of the North American
Prodrome Longitudinal Study (NAPLS), the multi-site research consortium
formed in 2003 to focus on early intervention and prevention of
schizophrenia. By pooling their data, NAPLS researchers have been able
to identify individuals at high risk for developing a psychotic disorder
as well as the biological risk factors associated with converting to
This summer, the collaborators, led by researchers at Yale,
published a risk calculator that can help professionals predict
patients' risk of developing psychosis. In addition to BIDMC and Yale,
the other NAPLS sites are based at Emory University, the University of
Calgary, University of California Los Angeles (UCLA), University of
California San Diego (UCSD), University of North Carolina Chapel Hill,
University of San Francisco, and Zucker Hillside Hospital.
"A significant number of people are able to remain in or go back to
work and school," Seidman said. "This early intervention approach is
giving people more hope, and that really matters."