| 1 | Hum. Mol. Genet. 2006 Jun 15: 1949-62 |
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| PMID | 16687443 |
| Title | Genome-wide expression analysis detects eight genes with robust alterations specific to bipolar I disorder: relevance to neuronal network perturbation. |
| Abstract | The limited number of genome-wide transcriptome analyses using the postmortem brains of bipolar disorder sufferers has not produced a clear consensus on the molecular pathways affected by the disorder. To expand the knowledge in this area, we examined the expression levels of more than 12 000 genes in Brodmann's Area (BA), 46 (dorsolateral prefrontal cortex) from bipolar I disorder and control samples using Affymetrix GeneChips. This analysis detected 108 differentially expressed genes in bipolar brains. Validation studies using quantitative RT-PCR on the two original diagnostic cohorts plus tissue from schizophrenic subjects, confirmed the differential expressions of eight genes (RAP1GA1, SST, HLA-DRA, KATNB1, PURA, NDUFV2, STAR and PAFAH1B3) in a bipolar-specific manner and one gene (CCL3) which was downregulated in both bipolar and schizophrenic brains. Of these, protein levels of RAP1GA1 (RAP1 GTPase activating protein 1) showed a trend of increase in BA46 from bipolar brains, in keeping with mRNA transcript levels. Transmission disequilibrium analysis of the nine genes using 43 single nucleotide polymorphisms (SNPs) in 229 National Institute of Mental Health bipolar trios exposed nominal SNP association and modest empirical haplotypic association (P=0.033) between SST (somatostatin) and disease. Finally, gene network analysis using the currently obtained expression data highlighted cellular growth and nervous system development pathways as potential targets in the molecular pathophysiology of bipolar disorder. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 2 | Prog. Neuropsychopharmacol. Biol. Psychiatry 2008 Apr 32: 710-4 |
| PMID | 18096286 |
| Title | Increased serum levels of CCL11/eotaxin in schizophrenia. |
| Abstract | Inflammatory and immune alterations occur and may be relevant in patients with schizophrenia. Chemokines are a subgroup of cytokines that play a major role in the recruitment of determined subsets of leukocytes into tissues. To date no study has evaluated whether levels of chemokines are altered in patients with schizophrenia. To evaluate serum levels of CC and CXC chemokines of schizophrenic patients and age- and gender-matched controls. Forty male institutionalized schizophrenic patients (mean+/-SD age, 52.3+/-9.9) and 20 asymptomatic matched controls were recruited for this study. Severity of symptoms was assessed using BPRS, PANSS and AIMS. All patients were under typical antipsychotic treatment. Serum concentrations of chemokines were measured by ELISA. There was no statistical difference in serum levels of CCL2, CCL3, CCL24, CXCL9 and CXCL10 between controls and patients. Serum levels of CCL11 were increased in schizophrenic patients when compared to controls. Serum levels of chemokines were not correlated with the length of disease or hospitalization and the severity of involuntary movements, positive and/or negative symptoms. CCL11 is a ligand for CCR3, a receptor expressed preferentially on Th2 lymphocytes, mast cells and eosinophils. Higher serum levels of CCL11 in schizophrenia reinforce the view that this disease may be associated with a Th1/Th2 imbalance with a shift toward a Th2 immune response. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 3 | Prog. Neuropsychopharmacol. Biol. Psychiatry 2008 Apr 32: 710-4 |
| PMID | 18096286 |
| Title | Increased serum levels of CCL11/eotaxin in schizophrenia. |
| Abstract | Inflammatory and immune alterations occur and may be relevant in patients with schizophrenia. Chemokines are a subgroup of cytokines that play a major role in the recruitment of determined subsets of leukocytes into tissues. To date no study has evaluated whether levels of chemokines are altered in patients with schizophrenia. To evaluate serum levels of CC and CXC chemokines of schizophrenic patients and age- and gender-matched controls. Forty male institutionalized schizophrenic patients (mean+/-SD age, 52.3+/-9.9) and 20 asymptomatic matched controls were recruited for this study. Severity of symptoms was assessed using BPRS, PANSS and AIMS. All patients were under typical antipsychotic treatment. Serum concentrations of chemokines were measured by ELISA. There was no statistical difference in serum levels of CCL2, CCL3, CCL24, CXCL9 and CXCL10 between controls and patients. Serum levels of CCL11 were increased in schizophrenic patients when compared to controls. Serum levels of chemokines were not correlated with the length of disease or hospitalization and the severity of involuntary movements, positive and/or negative symptoms. CCL11 is a ligand for CCR3, a receptor expressed preferentially on Th2 lymphocytes, mast cells and eosinophils. Higher serum levels of CCL11 in schizophrenia reinforce the view that this disease may be associated with a Th1/Th2 imbalance with a shift toward a Th2 immune response. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 4 | Transl Psychiatry 2014 -1 4: e406 |
| PMID | 24984193 |
| Title | Increased M1/decreased M2 signature and signs of Th1/Th2 shift in chronic patients with bipolar disorder, but not in those with schizophrenia. |
| Abstract | We here present data on immune gene expression of chemokines, chemokine receptors, cytokines and regulatory T-cell (T-reg) markers in chronic patients suffering from either schizophrenia (SCZ, N=20) or bipolar disorder (BD=20) compared with healthy controls (HCs, N=20). We extracted RNA from peripheral blood mononuclear cells and performed real-time (RT)-PCR to measure mRNA levels of chemokines, chemokine receptors, cytokines and T-reg markers. All the analyses were Bonferroni-corrected. The classical monocyte activation (M1) markers il6, CCL3 were significantly increased in BD as compared with both HC and SCZ patients (P=0.03 and P=0.002; P=0.024 and P=0.021, respectively), whereas markers of alternative (M2) monocyte activation ccl1, ccl22 and il10 were coherently decreased (controls: P=0.01, P=0.001 and P=0.09; SCZ subjects: P=0.02, P=0.05 and P=0.011, respectively). Concerning T-cell markers, BD patients had compared with HC downregulated ccr5 (P=0.02) and upregulated il4 (P=0.04) and compared with both healthy and SCZ individuals downregulated ccl2 (P=0.006 and P=0.003) and tgf? (P=0.004 and P=0.007, respectively). No significant associations were found between any immune gene expression and clinical variables (prior hospitalizations, Brief Psychiatric Rating Scale, medications' dosages and lifetime administration). Although some markers are expressed by different immune cell types, these findings suggest a coherent increased M1/decrease M2 signature in the peripheral blood of BD patients with potential Th1/Th2 shift. In contrast, all the explored immune marker levels were preserved in SCZ. Further larger studies are needed to investigate the relevance of inflammatory response in BD, trying to correlate it to psychopathology, treatment and outcome measures and, possibly, to brain connectivity. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 5 | Neurosci Biobehav Rev 2014 May 42: 93-115 |
| PMID | 24513303 |
| Title | Chemokines and chemokine receptors in mood disorders, schizophrenia, and cognitive impairment: a systematic review of biomarker studies. |
| Abstract | The search for immune biomarkers in psychiatric disorders has primarily focused on pro-inflammatory cytokines. Other immune proteins including chemokines have been relatively neglected in such studies. Recent evidence has implicated chemokines in many neurobiological processes potentially relevant to psychiatric disorders, beyond their classical chemotactic functions. These may include neuromodulator effects, neurotransmitter-like effects, and direct/indirect regulation of neurogenesis. This systematic review presents the existing early evidence which supports an association of many chemokines with the psychiatric disorders: depression, bipolar disorder, schizophrenia, mild cognitive impairment and Alzheimer's disease. The non-specific association of chemokines including CXCL8 (IL-8), CCL2 (MCP-1), CCL3 (MIP-1?) and CCL5 (RANTES) with these disorders across diagnostic categories implies a generalised involvement of many chemokine systemic with psychiatric disease. Additional chemokines with great mechanistic relevance including CXCL12 (SDF-1) and CX3CL1 (fractalkine) have been rarely reported in the existing human literature and should be included in future clinical studies. The potential utility of these proteins as pathologically relevant biomarkers or therapeutic targets should be considered by future clinical and translational research. |
| SCZ Keywords | schizophrenia, schizophrenic |