Functional magnetic resonance imaging of people considered to be at very high risk for schizophrenia suggests prefrontal function declines significantly before the onset of clinically defined disease, according to an article in the March issue of the Archives of General Psychiatry.

If further research confirms there are biologically definable changes in prefrontal cortex before high-risk individuals experience early symptoms of schizophrenia, diagnosing those changes may allow physicians to help these patients before their first psychotic episode.

"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.

The current study involved functional magnetic resonance imaging (fMRI) of frontal and striatal activity during a visual oddball continuous performance task in 52 participants who fit into one of four groups: ultra-high-risk for schizophrenia, early schizophrenia (less than 5 years), chronic schizophrenia (longer than 5 years), and healthy, age-matched controls.

People considered at ultra-high-risk were pre-screened for presence of some schizophrenia symptoms, such as early emotional, affective, and cognitive problems; these included blunting of emotion, poor personal relationships, poor hygiene, emotional detachment, and false beliefs.

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.

The researchers found that when healthy people make these types of detections and decisions, they activated 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 disease onset."

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."

"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 schizophrenia onset."