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Nikolaos Koutsouleris, MD; Eva M. Meisenzahl, MD; Christos Davatzikos, PhD; Ronald Bottlender, MD; Thomas Frodl, MD; Johanna Scheuerecker, BA; Gisela Schmitt, MD; Thomas Zetzsche, MD; Petra Decker, BA; Maximilian Reiser, MD; Hans-Jürgen Möller, MD; Christian Gaser, PhD

Arch Gen Psychiatry. 2009;66(7):700-712.

Context  Identification of individuals at high risk of developing psychosis has relied on prodromal symptomatology. Recently, machine learning algorithms have been successfully used for magnetic resonance imaging–based diagnostic classification of neuropsychiatric patient populations.

Objective  To determine whether multivariate neuroanatomical pattern classification facilitates identification of individuals in different at-risk mental states (ARMS) of psychosis and enables the prediction of disease transition at the individual level.

Design  Multivariate neuroanatomical pattern classification was performed on the structural magnetic resonance imaging data of individuals in early or late ARMS vs healthy controls (HCs). The predictive power of the method was then evaluated by categorizing the baseline imaging data of individuals with transition to psychosis vs those without transition vs HCs after 4 years of clinical follow-up. Classification generalizability was estimated by cross-validation and by categorizing an independent cohort of 45 new HCs.

Setting  Departments of Psychiatry and Psychotherapy, Ludwig-Maximilians-University, Munich, Germany.

Participants  The first classification analysis included 20 early and 25 late at-risk individuals and 25 matched HCs. The second analysis consisted of 15 individuals with transition, 18 without transition, and 17 matched HCs.

Main Outcome Measures  Specificity, sensitivity, and accuracy of classification.

Results  The 3-group, cross-validated classification accuracies of the first analysis were 86% (HCs vs the rest), 91% (early at-risk individuals vs the rest), and 86% (late at-risk individuals vs the rest). The accuracies in the second analysis were 90% (HCs vs the rest), 88% (individuals with transition vs the rest), and 86% (individuals without transition vs the rest). Independent HCs were correctly classified in 96% (first analysis) and 93% (second analysis) of cases.

Conclusions  Different ARMSs and their clinical outcomes may be reliably identified on an individual basis by assessing patterns of whole-brain neuroanatomical abnormalities. These patterns may serve as valuable biomarkers for the clinician to guide early detection in the prodromal phase of psychosis.

Author Affiliations: Departments of Psychiatry and Psychotherapy (Drs Koutsouleris, Meisenzahl, Bottlender, Frodl, Schmitt, Zetzsche, and Möller and Mss Scheuerecker and Decker) and Radiology (Dr Reiser), Ludwig-Maximilians-University, Munich, Germany; Section of Biomedical Image Analysis, Department of Radiology, University of Pennsylvania, Philadelphia (Dr Davatzikos); and Department of Psychiatry, Friedrich-Schiller-University, Jena, Germany (Dr Gaser).

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