title: Disease prediction in the at-risk mental state for psychosis using neuroanatomical biomarkers: results from the FePsy study.
abstract: BACKGROUND
  Reliable prognostic biomarkers are needed for the early recognition of psychosis. Recently, multivariate machine learning methods have demonstrated the feasibility to predict illness onset in clinically defined at-risk individuals using structural magnetic resonance imaging (MRI) data. However, it remains unclear whether these findings could be replicated in independent populations.
  
  
  METHODS
  We evaluated the performance of an MRI-based classification system in predicting disease conversion in at-risk individuals recruited within the prospective FePsy (Früherkennung von Psychosen) study at the University of Basel, Switzerland. Pairwise and multigroup biomarkers were constructed using the MRI data of 22 healthy volunteers, 16/21 at-risk subjects with/without a subsequent disease conversion. Diagnostic performance was measured in unseen test cases using repeated nested cross-validation.
  
  
  RESULTS
  The classification accuracies in the "healthy controls (HCs) vs converters," "HCs vs nonconverters," and "converters vs nonconverters" analyses were 92.3%, 66.9%, and 84.2%, respectively. A positive likelihood ratio of 6.5 in the converters vs nonconverters analysis indicated a 40% increase in diagnostic certainty by applying the biomarker to an at-risk population with a transition rate of 43%. The neuroanatomical decision functions underlying these results particularly involved the prefrontal perisylvian and subcortical brain structures.
  
  
  CONCLUSIONS
  Our findings suggest that the early prediction of psychosis may be reliably enhanced using neuroanatomical pattern recognition operating at the single-subject level. These MRI-based biomarkers may have the potential to identify individuals at the highest risk of developing psychosis, and thus may promote informed clinical strategies aiming at preventing the full manifestation of the disease.
authors.affiliation: Department of Psychiatry and Psychotherapy, Ludwig-Maximilian-University, Nussbaumstrasse 7, 80336 Munich, Germany. Nikolaos.Koutsouleris@med.uni-muenchen.de
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Koutsouleris
authors.forename: Stefan
authors.initials: S
authors.lastname: Borgwardt
authors.forename: Eva M
authors.initials: EM
authors.lastname: Meisenzahl
authors.forename: Ronald
authors.initials: R
authors.lastname: Bottlender
authors.forename: Hans-Jürgen
authors.initials: HJ
authors.lastname: Möller
authors.forename: Anita
authors.initials: A
authors.lastname: Riecher-Rössler
mesh_terms: D000328:Adult; D001185:Artificial Intelligence; D001921:Brain / Q000473:pathology*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods*; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D062706:Prodromal Symptoms; D011379:Prognosis; D011446:Prospective Studies; D011618:Psychotic Disorders / Q000175:diagnosis / Q000473:pathology; D012680:Sensitivity and Specificity
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