CONTACT: BECKY SOGLIN
2130 Medical Laboratories
Iowa City IA 52242
(319) 335-6660; fax (319) 335-8034
Release: Nov. 29, 1999
UI's Andreasen promotes unified concept of schizophrenia
IOWA CITY, Iowa -- Schizophrenia has many different
signs and symptoms, ranging from paranoid delusions to apathetic withdrawal.
Yet, it remains a question how this one illness can have so many different
manifestations -- and how it can more effectively be treated or prevented.
The answer may lie in brain circuitry, where misconnections
in how the brain is "wired" together may cause the misconnected thought that
typifies schizophrenia, according to a theory developed by Nancy C. Andreasen,
M.D., Ph.D., University of Iowa Health Care psychiatrist and director of the
UI Mental Health Clinical Research Center. Andreasen recently published her
first formal summary of her idea, a unitary model for schizophrenia.
"The clinical story -- the observations of misconnections
in how a person with schizophrenia thinks and feels -- matches a brain-related
story," said Andreasen, who has studied schizophrenia for more than 30 years.
She hopes that by publishing her model more researchers and physicians will
consider its implications for treatment and understanding of the illness.
Andreasen's concept of brain circuitry disruption
is a neuroscientific update of a theory set forth in the early 1900's by Eugen
Bleuler, a psychiatrist who practiced at Burgholzli Clinic in Switzerland.
Bleuler ascribed the term schizophrenia (literally, a "mind torn asunder")
to the illness in which patients had a substantial inability to think cogently.
He underscored this commonality of thought disorder, whether manifested through
the paranoid subgroup (in which a person falsely believes persecution or harm
is imminent), or the negative subgroup (in which a person is apathetic, silent
and devoid of emotion). However, Bleuler did not explain his theory in terms
of brain mechanisms.
About five years ago, Andreasen began to take Bleuler's
idea a step further and focus on what was "below the surface" rather than
the surface signs of schizophrenia. By 1997, using evidence she and other
researchers gathered through neuroimaging, she described a "misconnection
syndrome" between parts of the brain that causes the cognitive dysfunction
"People with schizophrenia are impaired in different
cognitive ways such as memory, attention and language," Andreasen said. "Yet
neuroimaging studies reveal dysfunction within the cortical regions, cerebellum
and thalamus no matter which cognitive function is involved."
The dysfunctional circuit is the cortico-cerebellar-thalamic-cortical
circuit. The cerebellum was previously thought to be involved primarily only
in coordination of motor activities. But researchers have found that the cerebellum
and thalamus also are involved in thought tasks.
Additional evidence suggests the cerebellum has extensive
cognitive functions, Andreasen said. For one, it is about one-third larger
in humans than in chimpanzees; however, our motor skills are not that much
more complex than theirs.
"Five years ago, 95 percent of researchers thought
it was wrong to consider the cerebellum as a major factor in schizophrenia,"
Andreasen said. "Now, that opinion is switched."
Andreasen seeks to understand how the brain of a person
with schizophrenia ends up in a misconnected state. Late adolescence, when
schizophrenia usually makes it onset, is a major and critical period for brain
"Between the ages of 15 and 30 the brain completes
its final wiring," Andreasen explained. "The axons and dendrites are in place,
but there is fine sculpting or pruning to ensure the nerves are connected
correctly. In schizophrenia, something seems to go wrong with this pruning,
and behind that is some kind of aberrant molecular regulation of late neurodevelopment."
Andreasen will continue to document her concept of
a unitary model and attempt to define more precisely the biomolecular mechanism
that makes the brain circuitry go wrong.
Her team, in conjunction with researchers at the University
of California in San Francisco, will also investigate how brain plasticity
-- the ways in which the brain is affected by biological and social environmental
factors -- may contribute to schizophrenia treatment.
"While some changes to the brain are irreversible,
the brain also has a wonderful capacity to change and adapt," Andreasen said.
"For people with mental illness we need to explore how much we can capitalize
on brain plasticity to develop treatments that augment pharmaceutical treatments."
Schizophrenia affects approximately 1 percent of the
population. Up to 10 percent of affected people eventually commit suicide.
Only a tiny percentage of people with schizophrenia are dangerous to others,
and people with the condition are overall less prone to violence than the
general population. While treatments can be effective, most people with schizophrenia
do not fully recover.
"It is interesting and promising to see changes in
public attitude toward schizophrenia over the past 15 years," Andreasen said.
"Like cancer, people used to talk about schizophrenia in a whisper, but now
people are talking about it more openly and raising awareness."
Andreasen's article on a unitary model of schizophrenia
was published in the September issue of the Archives of General Psychiatry.
Her work was supported in part by three grants and a Research Scientist Award
from the National Institute of Mental Health and by an Established Investigator
Award from the National Alliance for Research on Schizophrenia and Depression.
University of Iowa Health Care describes the partnership
between the UI College of Medicine and the UI Hospitals and Clinics and the
patient care, medical education and research programs and services they provide.