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Images of brain activity may identify the onset of
schizophrenia in people at high risk, according to a study at
the University of North Carolina.
Images of brain activity may hold clues to the onset of
schizophrenia in people at high risk for the disease,
according to a study headed by psychiatry researchers at the
University of North Carolina at Chapel Hill School of
The new findings appear in the March issue of the Archives of
General Psychiatry, a journal of the American Medical Association.
A decline in function in the prefrontal cortex, the "executive"
or front part of the brain, is present in high-risk individuals
experiencing early symptoms of schizophrenia and may reflect
biological changes that precede the onset of diagnosable illness,
the study indicates.
Identifying such changes prior to disease onset also may prove
useful in determining vulnerability to schizophrenia onset,
particularly in those at high risk for the disease, the researchers
"We know that individuals who experience symptoms that occur
before the disease becomes full-blown demonstrate impaired
performance in tasks requiring executive function, attention and
working memory, but the neurobiological bases of this remains
unclear," said Dr. Aysenil Belger, the study's senior author.
"In looking at the brain activity of high-risk people while they
performed some of these tasks, we hoped to identify a
neurobiological marker of vulnerability to disease onset, a tool we
might use to help assess their risk of developing psychotic
symptoms," Belger said. "If such a tool became established, perhaps
we could intervene early on in some way to improve whatever
pathology it showed."
Belger is an associate professor of psychiatry in UNC's School of
Medicine and of psychology in UNC's College of Arts and Sciences.
The study involved functional magnetic resonance imaging, or fMRI.
Unlike standard MRI scans that show anatomical structures in black
and white, fMRI offers digitally enhanced color images of brain
function, depicting localized changes in blood flow and oxygenation.
When particular regions of the brain increase their neural
activity in association with various actions or thought processes,
they emit enhanced blood oxygen level dependent signals. The signals
can be localized in the brain and translated into digital images
that portray neural activity level as a ratio of oxygenated to
de-oxygenated hemoglobin, the iron-containing pigment in red blood
cells. Researchers then can quantify these signals to generate maps
of various brain functions.
Fifty-two study participants were divided into four groups:
"ultra-high-risk," where participants experience symptoms but the
illness is not full-blown; early schizophrenia, where participants
have had the illness less than five years; chronic schizophrenia,
where participants have had the illness for more than five years;
and healthy age-matched "controls," for comparison.
Those at ultra-high-risk had been pre-screened for schizophrenia
symptoms, revealing that some were showing early emotional,
affective and cognitive symptoms such as the blunting of emotion,
poor personal relationships, poor hygiene, emotional detachment and
While undergoing fMRI scans, all participants responded to an
executive decision test - so-called because decision making and
task-appropriate response selection are required - displayed on a
computer screen. This test, developed by the study team, requires
push-button responses to certain colored squares, circles and
objects from everyday life. Each visual cue is presented at a
fraction of a second against a white background, and participants
must ignore an auditory tone sounded when each cue is presented.
"Of particular interest was the neural activity generated by a
series of infrequent circles that were designated as 'target'
events, which participants were instructed to detect and respond to
as quickly as possible by pressing a button," Belger said.
"Accurate and fast performance on this test requires both the
maintenance of attention and vigilance, as well as the ability to
rapidly discriminate between target events and other non-target
distracters, such as the colored squares and objects."
The scanner mapped participants' neural activity in specific
brain areas before, during and after the presentation of the visual
"Our goal was to see if the high-risk individuals showed normal
brain activity during these executive tasks or whether or not they
showed some of the pathology of individuals who already have
schizophrenia," Belger said.
The researchers found that when the healthy people make these
types of detections and decisions, they activate frontal and
mid-brain regions. Chronic schizophrenia patients showed a
significant drop in activation of these regions, "thus it appears
that they fail to engage these frontal regions," said Belger.
"And we found that the high-risk group and early, or
first-episode, schizophrenia group are somewhere in between: It
looks like these deficits begin even before they are diagnosed and
treated. It suggests that this area of the brain that's important
for executive decision-making processes is already altered before
The preliminary study represents a "first pass" at determining
feasibility of the tool to map tiny differences between patients and
controls, Belger said.
"We need to show that the tool is reliable and that, indeed, it's
detecting something in the population that it's not detecting in
healthy individuals," she added.
"This is also a cross-sectional study, a comparison between
groups. It's not longitudinal, as we did not study the same
individuals over time. Still, the findings are intriguing; they are
suggestive. We still need to know how they actually correlate with
Belger's UNC co-authors were Dr. Jeffrey Lieberman, who recently
left UNC to become chairman of psychiatry at Columbia University;
Dr. Diana Perkins, professor of psychiatry, and Dr. Seniha Inan,
postdoctoral fellow in psychiatry. Belger, Inan and Dr. Rajendra
Morey, clinical associate in psychiatry and behavioral sciences at
Duke University Medical Center, are also with the Duke-UNC Brain
Imaging and Analysis Center. Dr. Teresa Mitchell, also a co-author,
is assistant professor of psychiatry at the University of
Massachusetts Medical School.
Funding for the research came from the National Institute of
Mental Health, a component of the National Institutes of Health.
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