Schizophrenia Bulletin Advance Access published online on August 7, 2009
Schizophrenia Bulletin, doi:10.1093/schbul/sbp074
Prefrontal Function at Presentation Directly Related to Clinical Outcome in People at Ultrahigh Risk of Psychosis
2 Section of Neuroimaging, Division of Psychological Medicine, Institute of Psychiatry, King's College London, London, UK
3 Section of Psychiatry, Department of Health Sciences, University of Pavia, Pavia, Italy
4 Health Sciences Research Institute, Warwick Medical School, University of Warwick, Coventry, UK
5 Brain Image Analysis Unit, Department of Biostatistics and Computing, Institute of Psychiatry, King's College London, London, UK
1 To whom correspondence should be addressed; Section of Neuroimaging, Division of Psychological Medicine, PO67, Institute of Psychiatry, King's College London, De Crespigny Park 16, London SE58AF, UK; tel: +44-0-77-8666-6570, fax: +44-0-20-7848-0976, e-mail: p.fusar{at}libero.it.
Background: The prodromal phase of psychosis is characterized by impaired executive function and altered prefrontal activation. The extent to which the severity of these deficits at presentation predicts subsequent clinical outcomes is unclear. Methods: We employed functional magnetic resonance imaging in a cohort of subjects at clinical risk for psychosis and in healthy controls. Images were acquired at clinical presentation and again after 1 year, using a 1.5-T Signa MRI scanner while subjects were performing a verbal fluency task. SPM5 was used for the analysis of imaging data. Psychopathological assessment of the "at-risk" symptoms was performed by using the Comprehensive Assessment for the At-Risk Mental State (CAARMS) and the Positive and Negative Symptom Scale (PANSS). Results: In the at-risk mental state (ARMS) group, between presentation and follow-up, the CAARMS (perceptual disorder and thought disorder subscales) and the PANSS general scores decreased, while the Global Assessment of Functioning (GAF) score increased. Both the ARMS and control groups performed the verbal fluency task with a high degree of accuracy. The ARMS group showed greater activation in the left inferior frontal gyrus but less activation in the anterior cingulate gyrus than controls. Within the ARMS group, the longitudinal normalization of neurofunctional response in the left inferior frontal gyrus was positively correlated with the improvement in severity of hallucination-like experiences. Conclusions: The normalization of the abnormal prefrontal response during executive functioning is associated with 12-month psychopathological improvement of prodromal symptoms.
Keywords: prodromal psychosis / fMRI / executive functions / ARMS / cognition