The monocytes of a large proportion of bipolar patients and offspring of bipolar parents showed an inflammatory gene expression signature. This coherent set of genes opens new avenues for biomarker development with possibilities for disease prediction in individuals genetically at risk and for the subclassification of bipolar patients who could possibly benefit from anti-inflammatory treatment.

This review describes patients with schizophrenia and bipolar disorder. In such patients, a high inflammatory set point of circulating monocytes at the transcriptome level is observed, involving various inflammatory transcripts forming distinct fingerprints (the transcriptomic monocyte fingerprint in schizophrenia overlaps with that in bipolar disorder, but also differs with it at points). There are increased levels of compounds of the IL-1, IL-6 and TNF system in the serum (be it modest and inconsistent). There is also evidence that the IL-2 system is activated in patients with schizophrenia (and perhaps those with mania), although independently of the activation of the IL-1, IL-6 and TNF systems, suggesting separate inducing mechanisms for monocyte and T-cell activation. It is not yet known whether such T cell activation involves the Th1/Th2/Th17 or Treg systems.

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.

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OBJECTIVE— There is evidence that monocytes of patients with type 1 diabetes show proinflammatory activation and disturbed migration/adhesion, but the evidence is inconsistent. Our hypothesis is that monocytes are distinctly activated/disturbed in different subforms of autoimmune diabetes. RESEARCH DESIGN AND METHODS— We studied patterns of inflammatory gene expression in monocytes of patients with type 1 diabetes (juvenile onset, n = 30; adult onset, n = 30) and latent autoimmune diabetes of the adult (LADA) ( n = 30) (controls subjects, n = 49; type 2 diabetic patients, n = 30) using quantitative PCR. We tested 25 selected genes: 12 genes detected in a prestudy via whole-genome analyses plus an additional 13 genes identified as part of a monocyte inflammatory signature previously reported. RESULTS— We identified two distinct monocyte gene expression clusters in autoimmune diabetes. One cluster (comprising 12 proinflammatory cytokine/compound genes with a putative key gene PDE4B ) was detected in 60% of LADA and 28% of adult-onset type 1 diabetic patients but in only 10% of juvenile-onset type 1 diabetic patients. A second cluster (comprising 10 chemotaxis, adhesion, motility, and metabolism genes) was detected in 43% of juvenile-onset type 1 diabetic and 33% of LADA patients but in only 9% of adult-onset type 1 diabetic patients. CONCLUSIONS— Subgroups of type 1 diabetic patients show an abnormal monocyte gene expression with two profiles, supporting a concept of heterogeneity in the pathogenesis of autoimmune diabetes only partly overlapping with the presently known diagnostic categories.

The association of the monocyte pro-inflammatory state with BD is primarily the result of a common shared environmental factor.

Patients with schizophrenia show raised serum levels of the pro-inflammatory chemokine CCL2: Association with the metabolic syndrome in patients? Dear Editors, Serum levels of the pro-inflammatory cytokines IL-1β, IL-6 and TNF-α are raised in schizophrenia (Schuld et al., 2004). However, apart from these pro-inflammatory cytokines, chemokines play an important role in modulating brain function (Adler and Rogers, 2005). The system of chemokines and their receptors has been described as a major regulating system of the brain and the receptor for CCL2, CCR2, is expressed in the brain by astrocytes, microglia and neurons (Bajetto et al., 2002). CCL2 (Chemokine (C-C motif) ligand 2) is an important proinflammatory chemokine, playing a key role in the recruitment of monocytes to inflammatory foci (Kamei et al., 2006; Simeoni et al., 2004). Interestingly, a genotypic association was found between the A-2518G polymorphism of the CCL2 gene and resistance to anti-psychotic medication (Mundo et al., 2005) and a predominance of negative symptoms over positive symptoms (Pae et al., 2004). The A-2518G polymorphism affects the production of CCL2 (Mundo et al., 2005). However, it is unclear if CCL2 serum levels are changed in patients with schizophrenia. One study reported a normal level of CCL2 in the serum of a small group of institutionalized male patients (Teixeira et al., 2007), while another study reported an elevation of CCL2 in the cerebrospinal fluid of a small group of patients with psychosis serving as controls for a study on neuro-psychiatric lupus (Iikuni et al., 2006). Here we present a study on the CCL2 levels in the serum of 145 patients with chronic schizophrenia. Patients participated in a study on the prevalence of abnormalities in glucose metabolism in patients with schizophrenia or schizo-affective disorder treated with anti-psychotics; the demographic data, study design, hyperglycemia measurements, diabetes and metabolic syndrome definition and outcomes have been reported in detail before (Cohen et al.,

Our study provides an important tool to determine a shared, specific proinflammatory state of monocytes in AITD and LADA patients, enabling further research into the role of such proinflammatory cells in the failure to preserve tolerance in these conditions and of key fingerprint genes involved.