title: Towards a psychosis risk blood diagnostic for persons experiencing high-risk symptoms: preliminary results from the NAPLS project.
abstract: BACKGROUND
  A barrier to preventative treatments for psychosis is the absence of accurate identification of persons at highest risk. A blood test that could substantially increase diagnostic accuracy would enhance development of psychosis prevention interventions.
  
  
  METHODS
  The North American Prodrome Longitudinal Study project is a multisite endeavor that aims to better understand predictors and mechanisms for the development of psychosis. In this study, we measured expression of plasma analytes reflecting inflammation, oxidative stress, hormones, and metabolism. A "greedy algorithm" selected analytes that best distinguished persons with clinical high-risk symptoms who developed psychosis (CHR-P; n = 32) from unaffected comparison (UC) subjects (n = 35) and from those who did not develop psychosis during a 2-year follow-up (CHR-NP; n = 40).
  
  
  RESULTS
  The classifier included 15 analytes (selected from 117), with an area under the receiver operating curve for CHR-P vs UC of 0.91 and CHR-P vs CHR-NP of 0.88. Randomly scrambled group membership followed by reconstructions of the entire classifier method yielded consistently weak classifiers, indicating that the true classifier is highly unlikely to be a chance occurrence. Such randomization methods robustly imply the assays contain consistent information distinguishing the groups which was not obscured by the data normalization method and was revealed by classifier construction. These results support the hypothesis that inflammation, oxidative stress, and dysregulation of hypothalamic-pituitary axes may be prominent in the earliest stages of psychosis.
  
  
  CONCLUSIONS
  If confirmed in other groups of persons at elevated risk of psychosis, a multiplex blood assay has the potential for high clinical utility.
authors.affiliation: Department of Psychiatry, University of North Carolina, Chapel Hill, NC; diana_perkins@med.unc.edu.
authors.forename: Diana O
authors.initials: DO
authors.lastname: Perkins
authors.affiliation: Renaissance Computing Institute, University of North Carolina, Chapel Hill, NC;
authors.forename: Clark D
authors.initials: CD
authors.lastname: Jeffries
authors.affiliation: Department of Psychiatry, Hotchkiss Brain Institute, University of Calgary, Alberta, Canada;
authors.forename: Jean
authors.initials: J
authors.lastname: Addington
authors.affiliation: Departments of Psychiatry and Biobehavioral Sciences and Psychology, University of California, Los Angeles, Los Angeles, CA;
authors.forename: Carrie E
authors.initials: CE
authors.lastname: Bearden
authors.affiliation: Department of Psychiatry, University of California, San Diego, San Diego, CA;
authors.forename: Kristin S
authors.initials: KS
authors.lastname: Cadenhead
authors.affiliation: Department of Psychology, Yale University, New Haven, CT; Department of Psychiatry, Yale University, New Haven, CT.
authors.forename: Tyrone D
authors.initials: TD
authors.lastname: Cannon
authors.affiliation: Department of Psychiatry, Zucker Hillside Hospital, Long Island, NY.
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Cornblatt
authors.affiliation: Department of Psychiatry, University of California, San Francisco, San Francisco, CA;
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Mathalon
authors.affiliation: Department of Psychiatry, Yale University, New Haven, CT.
authors.forename: Thomas H
authors.initials: TH
authors.lastname: McGlashan
authors.affiliation: Department of Psychiatry, Harvard Medical School at Beth Israel Deaconess Medical Center and Massachusetts General Hospital, Boston, MA;
authors.forename: Larry J
authors.initials: LJ
authors.lastname: Seidman
authors.affiliation: Department of Psychiatry, Center for Behavioral Genomics, Institute of Genomic Medicine, University of California, San Diego, La Jolla, CA;
authors.forename: Ming T
authors.initials: MT
authors.lastname: Tsuang
authors.affiliation: Departments of Psychology and Psychiatry, Emory University, Atlanta, GA;
authors.forename: Elaine F
authors.initials: EF
authors.lastname: Walker
authors.affiliation: Department of Psychiatry, Yale University, New Haven, CT.
authors.forename: Scott W
authors.initials: SW
authors.lastname: Woods
authors.affiliation: Division of Adult Translational Research and Treatment Development, National Institute of Mental Health, Bethesda, MD.
authors.forename: Robert
authors.initials: R
authors.lastname: Heinssen
mesh_terms: D000328:Adult; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism*; D007249:Inflammation / Q000097:blood*; D008297:Male; D018384:Oxidative Stress / Q000502:physiology*; D010913:Pituitary-Adrenal System / Q000378:metabolism*; D062706:Prodromal Symptoms; D011618:Psychotic Disorders / Q000097:blood*; D018570:Risk Assessment; D055815:Young Adult
keywords: clinical high risk; immune; inflammation; malondialdehyde-modified low-density lipoprotein (MDA-LDL); multiplex; oxidative stress; prodrome; psychosis; risk prediction
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