MRI Scans Reveal Subtle Brain Differences In People With Schizophrenia, UF Researchers Find

September 9, 1999

GAINESVILLE—Scientists have tried through the years to attribute schizophrenia to one brain abnormality or another, but solid proof has been lacking. Now University of Florida researchers have found that subtle differences in 10 brain structures can provide a strong indicator of whether someone has the disorder.

In an article published in the current issue of the Journal of Biological Psychiatry, UF Brain Institute researchers report that by analyzing magnetic resonance imaging scans, they were able to correctly determine 77 percent of time which study participants had schizophrenia.

The finding holds promise as a tool for diagnosis or for predicting who might develop the often-devastating psychiatric illness, which typically first strikes in the late teens to early 30s. Useful in treatment, prediction also is critical in the quest to identify environmental contributions to schizophrenia.

“The first wave of MRI studies searched for the ‘smoking gun’ that could explain the symptoms of schizophrenia,” said Dr. John Kuldau, a professor of psychiatry in the UF College of Medicine and chief of psychiatry for the Malcom Randall Veterans Affairs Medical Center in Gainesville. “But the disease is much more complicated than that. Like diabetes, it is thought to be caused by an interplay between genetic and environmental factors.”

So instead of looking for one large difference between the groups, Kuldau and co-investigator Christiana Leonard, a professor of neuroscience, psychiatry and psychology, and the rest of their research team decided to examine a number of structures that had been proposed as playing a possible role in schizophrenia.

“If many genes are involved, one would expect them to produce proteins in different parts of the brain, resulting in subtle variations,” Kuldau said.

The researchers looked at overall brain volume and the placement or size of a variety of grooves, holes and folds in the brain. The differences were so slight between the 33 men in the control group and the 37 men with schizophrenia that they couldn’t be spotted by the eye. Instead, they were calculated with the help of statistical techniques.

“By looking at all these structures, we were able to do something we considered rather astonishing: accurately determine most of the time who in the study had schizophrenia just based on brain anatomy,” said Kuldau, who is now working to replicate the findings with other study participants.

An estimated 2.5 million people in the United States suffer from schizophrenia, a disorder characterized by delusions and hallucinations. People with the disorder often have a sense that they are being spied on or persecuted and report hearing voices that no one else does. Currently, there is no reliable predictor of the disease. Commonly, those with the disorder and their families deny anything is wrong for months or even years.

“Part of the illness is that you don’t recognize that you are sick, so there often is a big delay between onset and getting so sick that you come in for treatment,” Kuldau said.

The delay is problematic, because early medication treatment has been linked to improved long-term prognosis.

Kuldau said brain anatomy should be viewed as “an informative intermediary step” between genes and the development of schizophrenia, rather than as a direct cause. He noted that identical twins share the same genes, but they are exposed to different environmental influences, their brains can develop differently and often only one will develop the disease.

Kuldau said large-scale studies that track people for a number of years are needed to try to sort through all the possible contributors to the disorder.

“Only those sorts of studies will have the power to trace the path from genetic predisposition through physiologic, molecular and environmental contributions to the development of the behaviors associated with schizophrenia,” he said.