title: Prediction of transition from ultra-high risk to first-episode psychosis using a probabilistic model combining history, clinical assessment and fatty-acid biomarkers.
abstract: Current criteria identifying patients with ultra-high risk of psychosis (UHR) have low specificity, and less than one-third of UHR cases experience transition to psychosis within 3 years of initial assessment. We explored whether a Bayesian probabilistic multimodal model, combining baseline historical and clinical risk factors with biomarkers (oxidative stress, cell membrane fatty acids, resting quantitative electroencephalography (qEEG)), could improve this specificity. We analyzed data of a UHR cohort (n=40) with a 1-year transition rate of 28%. Positive and negative likelihood ratios were calculated for predictor variables with statistically significant receiver operating characteristic curves (ROCs), which excluded oxidative stress markers and qEEG parameters as significant predictors of transition. We clustered significant variables into historical (history of drug use), clinical (Positive and Negative Symptoms Scale positive, negative and general scores and Global Assessment of Function) and biomarker (total omega-3, nervonic acid) groups, and calculated the post-test probability of transition for each group and for group combinations using the odds ratio form of Bayes' rule. Combination of the three variable groups vastly improved the specificity of prediction (area under ROC=0.919, sensitivity=72.73%, specificity=96.43%). In this sample, our model identified over 70% of UHR patients who transitioned within 1 year, compared with 28% identified by standard UHR criteria. The model classified 77% of cases as very high or low risk (P>0.9, <0.1) based on history and clinical assessment, suggesting that a staged approach could be most efficient, reserving fatty-acid markers for 23% of cases remaining at intermediate probability following bedside interview.
authors.affiliation: Discipline of Psychiatry, Royal Adelaide Hospital, University of Adelaide, Adelaide, SA, Australia.
authors.forename: S R
authors.initials: SR
authors.lastname: Clark
authors.affiliation: Discipline of Psychiatry, Royal Adelaide Hospital, University of Adelaide, Adelaide, SA, Australia.
authors.forename: B T
authors.initials: BT
authors.lastname: Baune
authors.affiliation: Discipline of Psychiatry, Royal Adelaide Hospital, University of Adelaide, Adelaide, SA, Australia.
authors.forename: K O
authors.initials: KO
authors.lastname: Schubert
authors.affiliation: Orygen, The National Centre of Excellence in Youth Mental Health and Centre for Youth Mental Health, The University of Melbourne, Melbourne, VIC, Australia.
authors.forename: S
authors.initials: S
authors.lastname: Lavoie
authors.affiliation: Department of Psychiatry, University Hospital Jena, Jena, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Smesny
authors.affiliation: Orygen, The National Centre of Excellence in Youth Mental Health and Centre for Youth Mental Health, The University of Melbourne, Melbourne, VIC, Australia.
authors.forename: S M
authors.initials: SM
authors.lastname: Rice
authors.affiliation: Orygen, The National Centre of Excellence in Youth Mental Health and Centre for Youth Mental Health, The University of Melbourne, Melbourne, VIC, Australia.
authors.forename: M R
authors.initials: MR
authors.lastname: Schäfer
authors.affiliation: Department of Child and Adolescent Psychiatry, Medical University of Vienna, Vienna, Austria.
authors.forename: F
authors.initials: F
authors.lastname: Benninger
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria.
authors.forename: M
authors.initials: M
authors.lastname: Feucht
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria.
authors.forename: C M
authors.initials: CM
authors.lastname: Klier
authors.affiliation: Orygen, The National Centre of Excellence in Youth Mental Health and Centre for Youth Mental Health, The University of Melbourne, Melbourne, VIC, Australia.
authors.forename: P D
authors.initials: PD
authors.lastname: McGorry
authors.affiliation: Orygen, The National Centre of Excellence in Youth Mental Health and Centre for Youth Mental Health, The University of Melbourne, Melbourne, VIC, Australia.
authors.forename: G P
authors.initials: GP
authors.lastname: Amminger
mesh_terms: D000293:Adolescent; D001499:Bayes Theorem; D001714:Bipolar Disorder / Q000378:metabolism / Q000503:physiopathology / Q000523:psychology*; D002648:Child; D015331:Cohort Studies; D018450:Disease Progression; D004569:Electroencephalography; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008563:Membrane Lipids / Q000378:metabolism; D016017:Odds Ratio; D018384:Oxidative Stress; D011336:Probability; D062706:Prodromal Symptoms; D011618:Psychotic Disorders / Q000378:metabolism / Q000503:physiopathology / Q000523:psychology*; D012372:ROC Curve; D012306:Risk; D018570:Risk Assessment; D012563:Schizophrenia, Paranoid / Q000378:metabolism / Q000503:physiopathology / Q000523:psychology*; D055815:Young Adult
chemical_list: D005227:Fatty Acids; D008563:Membrane Lipids