Cited by 238Schizophrenia research and treatmentTryptophan and brain disordersPsychopathy, Forensic Psychiatry, Sexual Offending

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Towards a Psychosis Risk Blood Diagnostic for Persons Experiencing High-Risk Symptoms: Preliminary Results From the NAPLS Project

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Perkins, Diana O., Jeffries, Clark D., Addington, Jean, Bearden, Carrie E., Cadenhead, Kristin S., Cannon, Tyrone D., Cornblatt, Barbara A., Mathalon, Daniel H., McGlashan, Thomas H., Seidman, Larry J., Tsuang, Ming T., Walker, Elaine F., Woods, Scott W., Heinssen, Robert·2015·Schizophrenia Bulletin

DOI 10.1093/schbul/sbu099PMC PMC4332942

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Abstract

INTRODUCTION: 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. CONCLUSION: If confirmed in other groups of persons at elevated risk of psychosis, a multiplex blood assay has the potential for high clinical utility.

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Fig. 1. Shown analytes were the most frequently appearing in 20 5-by-5-by-5 cross-validation trials, each trial testing 125 partitions to generate ~80% subsets of UC, CHR-NP, and CHR-P samples.CC BY-NC · PubMed Central

Fig. 2. Fifteen-analyte receiver operating curves and 95% confidence intervals: (A) for CHR-P vs UC and (B) CHR-P vs CHR-NP.CC BY-NC · PubMed Central

Fig. 3. Distribution of AUCs for 100 classifiers built with random data. Shown is a beta distribution fit and P value (A) for UC vs CHR-P and (B) CHR-NP vs CHR-P. For UC vs P: the alpha values were >.2 for both Kolmogorov-Smirnov and Anderson-Darling tests of fit with beta distributions. Using the top 15, the area under the receiver operating curve (AUC) for true classifier on true data was 0.91. For the beta fit, this value is out of range and has a P value = 0. For NP vs P: the alpha values were >.2 for both Kolmogorov-Smirnov and Anderson-Darling tests of fit with beta distributions. Using the top 15, the AUC for true classifier on true data was 0.88. For the beta fit, this value has a P value = 6.51E-05.CC BY-NC · PubMed Central

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Authors: Perkins, D. O., Jeffries, C. D., Addington, J., Bearden, C. E., Cadenhead, K. S., Cannon, T. D., Cornblatt, B. A., Mathalon, D. H., McGlashan, T. H., Seidman, L. J., Tsuang, M. T., Walker, E. F., Woods, S. W., & Heinssen, R.
Affiliations: University of North Carolina at Chapel Hill (US)
University of Calgary (CA)
University of California, Los Angeles (US)
University of California San Diego (US)
Yale University (US)
Zucker Hillside Hospital (US)
University of California, San Francisco (US)
Beth Israel Deaconess Medical Center (US)
Emory University (US)
National Institute of Mental Health (US)
Corresponding author: Perkins, Diana O.
Jeffries, Clark D.
ORCID: Perkins, Diana O.
Jeffries, Clark D.
Addington, Jean
Bearden, Carrie E.
Cadenhead, Kristin S.
Cannon, Tyrone D.
Cornblatt, Barbara A.
Mathalon, Daniel H.
McGlashan, Thomas H.
Seidman, Larry J.
Tsuang, Ming T.
Walker, Elaine F.
Woods, Scott W.
Venue: Schizophrenia Bulletin
Publisher: Oxford University Press (OUP)
Published: 2014-08-06
Volume: 41
Issue: 2
Pages: 419-428
ISSN: 0586-7614 (ISSN-L)
1745-1701
DOI: 10.1093/schbul/sbu099
PMC: PMC4332942
OpenAlex: W2144107861
Cited by: 238
References: 60
Citations by year: 2026: 8 · 2025: 15 · 2024: 16 · 2023: 28 · 2022: 14 · 2021: 15 · 2020: 25 · 2019: 22 · 2018: 17 · 2017: 20 · 2016: 32 · 2015: 19 · 2014: 7
FWCI: 19.85
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc
Locations: Schizophrenia Bulletin (publishedVersion, cc-by-nc)
Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
PubMed Central (publishedVersion, cc-by-nc)
PubMed (publishedVersion)
Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
eScholarship (California Digital Library) (submittedVersion)
eScholarship (California Digital Library) (submittedVersion, cc-by-nc)
UNC Libraries
Funders: National Institute of Mental Health (U01MH081928, U01MH066160, U01MH082022, U01MH076989, U01MH081984, U01MH0818902, U01MH081857, U01MH082004, U01MH081944, P50MH066286, U01MH081988)
Topics: Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
Social Sciences › Psychology › Clinical Psychology › Psychopathy, Forensic Psychiatry, Sexual Offending
Keywords: psychosis risk, clinical high risk for psychosis
MeSH terms: Adult, Female, Follow-Up Studies, Humans, Hypothalamo-Hypophyseal System, Inflammation, Male, Pituitary-Adrenal System, Psychotic Disorders, Oxidative Stress, Risk Assessment, Young Adult, Prodromal Symptoms

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Towards a Psychosis Risk Blood Diagnostic for Persons Experiencing High-Risk Symptoms: Preliminary Results From the NAPLS Project

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