SCHIZOPHRENIA DIAGNOSIS: LEUKOCYTE MULTIGENE SIGNATURES

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This project will test the feasibility of a biological classification of schizophrenic patients and matched control subjects, based on high-density microarray measurement of transcribed white blood cell (leukocyte) RNA. Previous studies have shown associations between white blood cell (leukocyte) gene expression levels and schizophrenia, by measurement of mRNA transcripts for individual genes. The investigators hypothesize that patients with schizophrenia exhibit a characteristic leukocyte multigene expression pattern or signature that differs from normal healthy control subjects. This study is designed to generate multigene expression data from both neuroleptic-medicated and neuroleptic-naive schizophrenic patients, in order to avoid the potential confounder of neuroleptic drug-derived gene expression changes. The data generated in this study will be used to create a classifying multigene expression profile using clustering and supervised learning algorithms. The overall objective of this project is to successfully create a classifying, multigene marker profile for schizophrenia that can correctly distinguish both medicated and non-medicated schizophrenic patients from control subjects. Micro-array analysis will be performed to measure the gene expression in leukocyte samples from 20 neuroleptic-naive schizophrenic patients, 12 neuroleptic-treated schizophrenic patients, and 14 age- matched healthy control subjects. To recruit neuroleptic-naive patient subjects, the investigators will screen schizophrenic patients who present at the Bellevue Hospital Center Comprehensive Psychiatric Emergency Program (CPEP), and Rockland County local community facilities. To recruit medicated schizophrenic subjects they will screen Schizophrenic patients who present at Rockland Psychiatric Center (RPC), Orangeburg, New York. Control subjects will be recruited through the Nathan Kline Institute Healthy Volunteer Pool (NKI HVP). The specific aims are as follows: 1a) To collect blood leukocytes from twenty neuroleptic-na¿ve schizophrenics, twelve medicated schizophrenics, and fourteen age-matched healthy control subjects over the two-year period of this project. 1b) Employ Affymetrix GeneChip microarray technology to measure global gene expression in the leukocyte samples. 2) To combine the leukocyte gene expression datasets from our preliminary study (n=12) with that of this project (n=46), and use clustering and classification algorithms to identify and validate multi-gene fingerprints that differentiate schizophrenic subjects from normal healthy controls.