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Rajendra A. Morey, MD, MS; Seniha Inan, MD; Teresa V. Mitchell, PhD; Diana O. Perkins, MD, MPH; Jeffrey A. Lieberman, MD; Aysenil Belger, PhD

Arch Gen Psychiatry. 2005;62:254-262.

Context  Individuals experiencing prodromal symptoms of schizophrenia (ultra-high-risk group) demonstrate impaired performance on tasks of executive function, attention, and working memory. The neurobiological underpinnings of such executive deficits in ultra-high-risk individuals remains unclear.

Objective  We assessed frontal and striatal functions during a visual oddball continuous performance task, in ultra-high-risk, early, and chronic schizophrenic patients with the use of functional magnetic resonance imaging.

Design  Cross-sectional case-control design.

Setting  Community; outpatient clinic.

Patients  Fifty-two individuals (control, n = 16; ultra-high risk, n = 10; early, n = 15; chronic, n = 11) from a referred clinical sample and age- and sex-matched control volunteers underwent scanning.

Main Outcome Measures  Percentage of active voxels and percentage signal change calculated for the anterior cingulate gyrus (ACG), middle frontal gyrus (MFG), inferior frontal gyrus (IFG), basal ganglia, and thalamus. Performance on the visual oddball task was measured with percentage of hits and d' (a measure based on the hit rate and the false-alarm rate).

Results  The ultra-high-risk group showed significantly smaller differential activation between task-relevant and task-irrelevant stimuli in the frontal regions (ACG, IFG, MFG) than the control group. Frontostriatal activation associated with target stimuli in the early and chronic groups was significantly lower than the control group, while the ultra-high-risk group showed a trend toward the early group.

Conclusions  Our findings suggest that prefrontal function begins to decline before the onset of syndromally defined illness and hence may represent a vulnerability marker in assessing the risk of developing psychotic disorders among ultra-high-risk individuals.

Author Affiliations: Duke-UNC Brain Imaging and Analysis Center, Durham, NC (Drs Morey, Inan, and Belger); Department of Psychiatry, University of North Carolina at Chapel Hill (Drs Inan, Perkins, Lieberman, and Belger); E. K. Shriver Center, University of Massachusetts Medical School, Waltham (Dr Mitchell); and Department of Psychiatry and Behavioral Sciences, Duke University, Durham (Dr Morey).

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