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Identification of Targeted Analyte Clusters for Studies of Schizophrenia*

https://doi.org/10.1074/mcp.M900372-MCP200Get rights and content
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The search for biomarkers to diagnose psychiatric disorders such as schizophrenia has been underway for decades. Many molecular profiling studies in this field have focused on identifying individual marker signals that show significant differences in expression between patients and the normal population. However, signals for multiple analyte combinations that exhibit patterned behaviors have been less exploited. Here, we present a novel approach for identifying biomarkers of schizophrenia using expression of serum analytes from first onset, drug-naïve patients and normal controls. The strength of patterned signals was amplified by analyzing data in reproducing kernel spaces. This resulted in the identification of small sets of analytes referred to as targeted clusters that have discriminative power specifically for schizophrenia in both human and rat models. These clusters were associated with specific molecular signaling pathways and less strongly related to other neuropsychiatric disorders such as major depressive disorder and bipolar disorder. These results shed new light concerning how complex neuropsychiatric diseases behave at the pathway level and demonstrate the power of this approach in identification of disease-specific biomarkers and potential novel therapeutic strategies.

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*

This work was supported by the Stanley Medical Research Institute.

The on-line version of this article (available at http://www.mcponline.org) contains supplemental Figs. S1–S3 and Table S1.

1

The abbreviations used are:

    DSM

    Diagnostic and Statistical Manual of Mental Disorders

    AKT

    protein kinase B

    BD

    bipolar disorder

    ERK

    extracellular signal-regulated kinase

    FDA

    Fisher's discrimination analysis

    GH

    growth hormone

    GLP-1

    glucagon-like peptide-1

    LH

    luteinizing hormone

    MDD

    major depressive disorder

    PCA

    principal component analysis

    PCP

    phencyclidine

    TAC

    targeted analyte cluster

    MAP

    Multi-Analyte Profiling

    SZ

    schizophrenia

    BMI

    body mass index

    ACTH

    adrenocorticotropic hormone

    QC

    quality control

    FA

    factor analysis

    IPKB

    Ingenuity Pathways Knowledge Base

    IRS1

    insulin receptor substrate 1.

Jointly funded by the United States-United Kingdom International Technology Alliance and the European Union FP7 SocialNets project.