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Identification of blood biomarkers for psychosis using convergent functional genomics

Molecular Psychiatry volume 16, pages 37–58 (2011)Cite this article

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Abstract

There are to date no objective clinical laboratory blood tests for psychotic disease states. We provide proof of principle for a convergent functional genomics (CFG) approach to help identify and prioritize blood biomarkers for two key psychotic symptoms, one sensory (hallucinations) and one cognitive (delusions). We used gene expression profiling in whole blood samples from patients with schizophrenia and related disorders, with phenotypic information collected at the time of blood draw, then cross-matched the data with other human and animal model lines of evidence. Topping our list of candidate blood biomarkers for hallucinations, we have four genes decreased in expression in high hallucinations states (Fn1, Rhobtb3, Aldh1l1, Mpp3), and three genes increased in high hallucinations states (Arhgef9, Phlda1, S100a6). All of these genes have prior evidence of differential expression in schizophrenia patients. At the top of our list of candidate blood biomarkers for delusions, we have 15 genes decreased in expression in high delusions states (such as Drd2, Apoe, Scamp1, Fn1, Idh1, Aldh1l1), and 16 genes increased in high delusions states (such as Nrg1, Egr1, Pvalb, Dctn1, Nmt1, Tob2). Twenty-five of these genes have prior evidence of differential expression in schizophrenia patients. Predictive scores, based on panels of top candidate biomarkers, show good sensitivity and negative predictive value for detecting high psychosis states in the original cohort as well as in three additional cohorts. These results have implications for the development of objective laboratory tests to measure illness severity and response to treatment in devastating disorders such as schizophrenia.

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Acknowledgements

This work was supported by funds from INGEN (Indiana Genomics Initiative of Indiana University), INBRAIN (Indiana Center for Biomarker Research In Neuropsychiatry) and NARSAD Young Investigator Award to ABN, as well as NIMH R01 MH071912–01 to MTT and ABN. ABN would like to thank Howard Edenberg for excellent help and advice with animal model microarray data, as well as Sudharani Mamidipalli, Griffin Fitzgerald and Jesse Townes for their precise work with database maintenance and data analysis. Most importantly, we would like to thank the subjects who participated in these studies, their families and their caregivers. Without their generous participation, such work to advance the understanding of mental illness would not be possible.

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Author notes

  1. S M Kurian, H Le-Niculescu and S D Patel: These authors contributed equally to the work.

Authors and Affiliations

  1. Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA, USA

    S M Kurian, N J Schork & D R Salomon

  2. Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, USA

    H Le-Niculescu, S D Patel, D Bertram, J Davis, C Dike, N Yehyawi, J Dustin, D K Lahiri, J I Nurnberger Jr & A B Niculescu

  3. Indianapolis VA Medical Center, Indianapolis, IN, USA

    D Bertram, J Davis, C Dike, N Yehyawi, P Lysaker & A B Niculescu

  4. Department of Psychiatry, UC San Diego, La Jolla, CA, USA

    M Caligiuri, J Lohr, M A Geyer & M T Tsuang

  5. Department of Psychiatry, SUNY Upstate Medical University, Syracuse, NY, USA

    S V Faraone

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  1. S M Kurian
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  18. D R Salomon
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Correspondence to A B Niculescu.

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Competing interests

ABN and DRS are founders and hold an equity interest in Mindscape Diagnostics, Inc. MAG holds an equity interest in San Diego Instruments, Inc.

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Supplementary Information accompanies the paper on the Molecular Psychiatry website

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Kurian, S., Le-Niculescu, H., Patel, S. et al. Identification of blood biomarkers for psychosis using convergent functional genomics. Mol Psychiatry 16, 37–58 (2011). https://doi.org/10.1038/mp.2009.117

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