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UI psychiatry researcher authors paper in Science

IOWA CITY, Iowa -- Mental illnesses are often thought of as only affecting the "mind" -- emotions, thought and other mental activity expressed by the brain. Therefore, these illnesses are relatively difficult to understand.

But this perception is changing. Scientists are mapping the brain as the organ of the mind, and a convergence of findings indicates that mental illnesses can best be understood as dysfunctions in the neural circuitry connecting specific brain regions, according to a University of Iowa College of Medicine investigator recognized for her work on neuroimaging and schizophrenia.

In an article published in the March 14 issue of Science, Dr. Nancy Andreasen, UI professor and Andrew H. Woods Chair of Psychiatry, presents integrative models for both schizophrenia and depression that derive from work in psychiatry, neuroimaging, cognitive psychology, neuropsychology and neurobiology.

The perplexing challenge of schizophrenia, she says, is to explain how and why patients have so many different kinds of symptoms -- hearing voices, feeling persecuted, or experiencing intellectual or emotional emptiness. Andreasen argues that, based on her own research and that of other scientists working in a variety of disciplines, this diversity of symptoms can be explained by a single underlying brain mechanism.

"Basically, we are starting to recognize that schizophrenia is caused by an abnormality in a specific but distributed circuitry in the brain, which in turn affects basic cognitive processes, such as the mental coordination of ideas or the use of abstract concepts to guide behavior," Andreasen says. Her own studies and those of several other investigators -- using neuroimaging techniques, animal models or lesion methods -- point to a cognitive dysfunction based on a "misconnection syndrome" between the prefrontal cortex and other interconnected cortical and subcortical regions, particularly the thalamus and the cerebellum.

The idea that schizophrenia reflects an abnormality in brain circuitry, and should be studied in terms of a fundamental underlying process that links together a diversity of symptoms, is still a relatively new concept, Andreasen notes.

"The localization approach -- trying to link symptoms like hallucinations, delusions or disorganized language to specific brain regions -- was the thread of my research for more than 15 years," she says. "But it hit me about five years ago that this was not an efficient approach. The diversity of symptoms in schizophrenia probably reflects a single underlying brain process. My goal is to help identify that process."

As for research on depression, Andreasen also proposes an integrative model. The fundamental alteration in depression is in the experience of emotion, which probably reflects the enduring influence of painful memories, she says. Conditioning and lesion studies in animals and in humans suggest a role for the limbic circuitry that encodes emotional memories. Positron emission tomography (PET) studies suggest that these memories may lie dormant in a particular brain region known as the amygdala. They become active and release the cognitive experience of depression when frontal regions take notice of them. Treatment of depression, either with medications or psychotherapy, corrects the dysfunctional frontal-amygdala circuit.

Andreasen does not underestimate the impact neuroimaging technology such as PET -- which her research team uses to measure brain blood flow in patients with schizophrenia, and during emotional experiences such as pleasure or pain -- has had in her work. "We couldn't do what we're doing without these techniques. These are tools that allow us to take 'brain' and translate it into 'mind,'" she says. "With advanced neuroimaging, scientists can study how the brain functions with something as simple as tapping one's fingers, and something as complex as what happens when someone writes a poem."

Andreasen, director of the Mental Health Clinical Research Center (MHCRC) at the UI Hospitals and Clinics, is recognized around the world for her studies on schizophrenia and neuroimaging. In the Science article, she writes that advances in the study of schizophrenia and depression illustrate the power of developing cognitive models that arrive from different scientific approaches, terminology and techniques.

She and her colleagues at the Image Processing Laboratory at the MHCRC have also used imaging technology to create the cover artwork for the Science issue. Using surface analysis software developed by the UI team, the image depicts the brain of a schizophrenia patient. The brain is shown sectioned in half, with the scan of the internal anatomy of the brain in the top half. The bottom half, however, reveals a painting by 15th-century artist Hieronymous Bosch, conveying the subjective nature of the psychotic experience.


EDITORS NOTE: Dr. Andreasen is in Europe for the next several weeks. However, reporters can send her questions via e-mail ( or contact her UI office at (319) 356-1553.