title: Using genetic, cognitive and multi-modal neuroimaging data to identify ultra-high-risk and first-episode psychosis at the individual level.
abstract: BACKGROUND
  Group-level results suggest that relative to healthy controls (HCs), ultra-high-risk (UHR) and first-episode psychosis (FEP) subjects show alterations in neuroanatomy, neurofunction and cognition that may be mediated genetically. It is unclear, however, whether these groups can be differentiated at single-subject level, for instance using the machine learning analysis support vector machine (SVM). Here, we used a multimodal approach to examine the ability of structural magnetic resonance imaging (sMRI), functional MRI (fMRI), diffusion tensor neuroimaging (DTI), genetic and cognitive data to differentiate between UHR, FEP and HC subjects at the single-subject level using SVM.
  
  
  METHODS
  Three age- and gender-matched SVM paired comparison groups were created comprising 19, 19 and 15 subject pairs for FEP versus HC, UHR versus HC and FEP versus UHR, respectively. Genetic, sMRI, DTI, fMRI and cognitive data were obtained for each participant and the ability of each to discriminate subjects at the individual level in conjunction with SVM was tested.
  
  
  RESULTS
  Successful classification accuracies (p < 0.05) comprised FEP versus HC (genotype, 67.86%; DTI, 65.79%; fMRI, 65.79% and 68.42%; cognitive data, 73.69%), UHR versus HC (sMRI, 68.42%; DTI, 65.79%), and FEP versus UHR (sMRI, 76.67%; fMRI, 73.33%; cognitive data, 66.67%).
  
  
  CONCLUSIONS
  The results suggest that FEP subjects are identifiable at the individual level using a range of biological and cognitive measures. Comparatively, only sMRI and DTI allowed discrimination of UHR from HC subjects. For the first time FEP and UHR subjects have been shown to be directly differentiable at the single-subject level using cognitive, sMRI and fMRI data. Preliminarily, the results support clinical development of SVM to help inform identification of FEP and UHR subjects, though future work is needed to provide enhanced levels of accuracy.
authors.affiliation: Department of Psychosis Studies, King's College London, Institute of Psychiatry, De Crespigny Park, London, UK.
authors.forename: W
authors.initials: W
authors.lastname: Pettersson-Yeo
authors.forename: S
authors.initials: S
authors.lastname: Benetti
authors.forename: A F
authors.initials: AF
authors.lastname: Marquand
authors.forename: F
authors.initials: F
authors.lastname: Dell'acqua
authors.forename: S C R
authors.initials: SC
authors.lastname: Williams
authors.forename: P
authors.initials: P
authors.lastname: Allen
authors.forename: D
authors.initials: D
authors.lastname: Prata
authors.forename: P
authors.initials: P
authors.lastname: McGuire
authors.forename: A
authors.initials: A
authors.lastname: Mechelli
mesh_terms: D000328:Adult; D001921:Brain / Q000473:pathology / Q000503:physiopathology; D056324:Diffusion Tensor Imaging; D005260:Female; D059907:Functional Neuroimaging; D005838:Genotype; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D064847:Multimodal Imaging / Q000295:instrumentation / Q000379:methods*; D009483:Neuropsychological Tests; D011618:Psychotic Disorders / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D012306:Risk; D012680:Sensitivity and Specificity; D060388:Support Vector Machine; D013997:Time Factors; D055815:Young Adult