The International Journal of Neuropsychopharmacology

Research Article

Inflammatory gene expression in monocytes of patients with schizophrenia: overlap and difference with bipolar disorder. A study in naturalistically treated patients

Roosmarijn C. Drexhagea1 c1, Leonie van der Heul-Nieuwenhuijsena1, Roos C. Padmosa1, Nico van Beverena2, Dan Cohena3a4, Marjan A. Versnela1, Willem A. Nolena5 and Hemmo A. Drexhagea1

a1 Department of Immunology, Erasmus MC, Rotterdam, The Netherlands

a2 Department of Psychiatry, Erasmus MC, Rotterdam, The Netherlands

a3 Department of Epidemiology, University Medical Center, Groningen, The Netherlands

a4 GGZ-NHN, Heerhugowaard, The Netherlands

a5 Department of Psychiatry, University Medical Center, Groningen, The Netherlands

Abstract

Accumulating evidence indicates an activated inflammatory response system as a vulnerability factor for schizophrenia (SZ) and bipolar disorder (BD). We aimed to detect a specific inflammatory monocyte gene expression signature in SZ and compare such signature with our recently described inflammatory monocyte gene signature in BD. A quantitative-polymerase chain reaction (Q-PCR) case-control gene expression study was performed on monocytes of 27 SZ patients and compared to outcomes collected in 56 BD patients (all patients naturalistically treated). For Q-PCR we used nine ‘SZ specific genes’ (found in whole genome analysis), the 19 BD signature genes (previously found by us) and six recently described autoimmune diabetes inflammatory monocyte genes. Monocytes of SZ patients had (similar to those of BD patients) a high inflammatory set point composed of three subsets of strongly correlating genes characterized by different sets of transcription/MAPK regulating factors. Subset 1A, characterized by ATF3 and DUSP2, and subset 1B, characterized by EGR3 and MXD1, were shared between BD and SZ patients (up-regulated in 67% and 51%, and 34% and 41%, respectively). Subset 2, characterized by PTPN7 and NAB2 was up-regulated in the monocytes of 62% BD, but down-regulated in the monocytes of 48% of SZ patients. Our approach shows that monocytes of SZ and BD patients overlap, but also differ in inflammatory gene expression. Our approach opens new avenues for nosological classifications of psychoses based on the inflammatory state of patients, enabling selection of those patients who might benefit from an anti-inflammatory treatment.

(Received February 08 2010)

(Reviewed April 22 2010)

(Revised May 11 2010)

(Accepted June 08 2010)

(Online publication July 15 2010)

Correspondence:

c1 Address for correspondence: R. C. Drexhage, M.D., Department of Immunology, Erasmus MC, PO Box 2040, 3000CA Rotterdam, The Netherlands. Tel.: 0031 10 7044091 Fax: 0031 10 7044731 Email: r.drexhage@erasmusmc.nl

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