Functional Imaging in Youth at Risk for Transdiagnostic Serious Mental Illness: Initial Results from the PROCAN Study

Background: In their early stages, serious mental illnesses (SMIs) are often indistinguishable from one another, suggesting that studying alterations in brain activity in a transdiagnostic fashion could help to understand the neurophysiological origins of different SMI. The purpose of this study was to examine brain activity in youth at varying stages of risk for SMI using functional magnetic resonance imaging tasks (fMRI) that engage brain systems believed to be affected.

Methods: Two hundred and forty three participants at different stages of risk for SMI were recruited to the Canadian Psychiatric Risk and Outcome (PROCAN) study, however only 179 were scanned. Stages included asymptomatic participants at no elevated risk, asymptomatic participants at elevated risk due to family history, participants with undifferentiated general symptoms of mental illness, and those experiencing attenuated versions of diagnosable psychiatric illnesses. The fMRI tasks included: (1) a monetary incentive delay task; (2) an emotional Go-NoGo and (3) an n-back working memory task.

Results: Strong main effects with each of the tasks were found in brain regions previously described in the literature. However, there were no significant differences in brain activity between any of the stages of risk for SMI for any of the task contrasts, after accounting for site, sex and age. Furthermore, results indicated no significant differences even when participants were dichotomized as asymptomatic or symptomatic.

Conclusions: These results suggest that univariate BOLD responses during typical fMRI tasks are not sensitive markers of SMI risk and that further study, particularly longitudinal designs, will be necessary to understand brain changes underlying the early stages of SMI.