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Release: July 25, 2001

UI researchers find link between altered sense of smell and schizophrenia

IOWA CITY, Iowa -- Enjoying good smells or avoiding bad ones is one of the most basic human drives. However, people who have schizophrenia have difficulty recognizing good smells even though they experience bad smells to a similar degree as healthy people do, according to an investigation involving University of Iowa Health Care researchers.

In addition, the team found that the brains of people with schizophrenia work completely differently when it comes to smelling odors, good or bad, compared to the brain functioning of healthy volunteers. The findings will appear in the July 25 issue of the Journal of the American Medical Association.

While previous studies have looked at cognitive functions, such as memory and attention, of people with schizophrenia, this investigation is believed to be the first study to use neuroimaging techniques to look at anhedonia, or how people with schizophrenia are impaired in their ability to experience pleasure and express emotion, said Nancy C. Andreasen, M.D., Ph.D., the Andrew H. Woods Chair of Psychiatry at the UI and principal investigator of one of the grants that funded the study.

"Smell is a very basic drive in combination with appetite and sexual drive," Andreasen said. "If you want to sell a house, you try to have a smell of home-baked bread because it makes the home more appealing. If we want to say something is terrible, we say it 'stinks.'

"We found that people with schizophrenia could not recognize good smells even though they recognized the bad smells just as healthy volunteers did. This is consistent with what we see at the clinical level, where people with schizophrenia have lost the ability to experience pleasure. It also adds more evidence that schizophrenia is a brain disease that affects connections between areas of the brain."

The study focused on how 18 people with schizophrenia and 16 healthy volunteers reacted to good and bad smells, a vanilla odor and an acidic odor, respectively. The research team directly

measured the participants' brain activity using positron-emission tomography (PET) while they were smelling the different odors. PET maps brain blood flow so that researchers can see how blood

moves from one brain region to another depending on the mental activities a person is performing. The patients and healthy subjects were chosen based on equivalent smoking histories in order to avoid differences caused by an impaired sense of smell.

The team found that healthy subjects used a primitive part of the brain called the limbic system, or the "nose brain," to recognize bad smells. These same healthy people used a more advanced part of the brain, the frontal lobe, to recognize good smells. However, people with schizophrenia did not follow this pattern of using the primitive brain to recognize bad odors and the higher part of the brain to recognize good or pleasurable odors.

"In a fascinating reversal, people with schizophrenia used the frontal, or advanced part of the brain, to recognize bad smells," Andreasen said. "It's as if the frontal region gets hijacked for this evolutionary task of recognizing bad smells, and the ability of the frontal region to experience pleasurable smells is lost."

She added, "So people with schizophrenia can recognize bad smells, which is important for survival. But they pay a price for using their frontal lobe instead of the more primitive part. They have anhedonia, or the loss of the ability to experience pleasure."

Andreasen said the research points to how investigators need to do more studies that bridge the clinical and biological bases of schizophrenia. She said the findings could have implications for understanding certain behaviors in people with the condition.

"In this particular case involving the recognition of bad odors, it's as if the brain were really tuned to recognize danger. It has to be highly vigilant," she said. "That same mechanism could explain why being highly tuned to recognize danger might lead people to misperceive an inter-personal experience or a particular other person as dangerous."

Andreasen emphasized the importance of positron-emission tomography in helping investigators see which brain areas are activated by a particular task or which areas have increased blood flow because a certain mental activity is being performed.

"PET is a very sensitive technique to determine what brain areas are involved in thought and feelings," said Andreasen, who recently published a new book, "Brave New Brain: Conquering Mental Illness in the Era of the Genome," which includes extensive explanations and illustrations of PET.

"An analogy would be to think about how, if you're running, more blood flows to your legs, but if you've just had lunch, the blood shifts to the stomach to aid digestion. That process in the brain is more fine-grained, and PET allows us to see it."

The primary author for the UI-based study was Benedicto Crespo-Facorro, M.D., Ph.D., who was a visiting post-doctoral fellow from the Hospital Universitario Marques de Valdecilla in Santander, Spain. In addition to Andreasen, UI researchers making up the primary research team included Sergio Paradiso, M.D., Ph.D., UI assistant professor of psychiatry, and Daniel S. O'Leary, Ph.D., a research scientist in psychiatry.

The investigation was supported in part by grants from the UI Mental Health Clinical Research Center, the National Institute of Mental Health, and the National Alliance for Research of Schizophrenia and Affective Disorders.

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.