Pattern of activation during delayed matching to sample task predicts functional outcome in people at ultra high risk for psychosis

Background: Clinical outcomes in people identified as at ultra-high risk (UHR) for psychosis are remarkably heterogeneous, and are difficult to predict on the basis of the presenting clinical features. Individuals at UHR are at risk of poor functional outcome regardless of development of psychotic disorder. The aim of the present study was to assess whether there is a relationship between functional neuroimaging measures at presentation and functional outcome as measured by the GAF three years after scanning.

Methods: Functional magnetic resonance imaging (fMRI) data were collected during an object working memory task in 34 ultra-high risk (UHR) subjects and 20 healthy controls. On the basis of their GAF scores at follow up, the UHR participants were divided into subgroups with good and poor functional outcomes, respectively.

Results: At baseline, the UHR group differed from controls in showing altered frontal and cuneus/posterior cingulate activation. Significant group x task interactions were found in the left cuneus and posterior cingulate gyrus, reflecting differential responses to the task conditions. Within the UHR sample, the subgroup with a poor functional outcome exhibited altered activation in frontal, temporal and striatal regions, and reduced deactivation within default-mode network regions, relative to those with a good outcome. Within the whole UHR sample, in these regions the local task response was correlated with the GAF score at follow up.

Conclusions: The findings suggest a potential role of functional neuroimaging in the prediction of outcomes in people at high clinical risk of psychosis.