Serum Levels and in vitro CX3CL1 (Fractalkine), CXCL8, and IL-10 Synthesis in Phytohemaglutinin-Stimulated and Non-stimulated Peripheral Blood Mononuclear Cells in Subjects With Schizophrenia.

Introduction: Although schizophrenia is a severe mental illness, whose etiology is still largely unknown, its pathogenesis may be associated with dysregulation of the immune mechanisms. The present study compares the levels of interleukin (IL)-10, interleukin-8 (CXCL8), and fractalkine (CX3CL1) between schizophrenia patients and healthy controls. It also assesses the ability of peripheral peripheral blood mononuclear cells (PBMCs) to produce these cytokines spontaneously and following mitogen-stimulation. Materials and Methods: A prospective study was performed of 60 adult schizophrenia patients and 32 controls. CXCL8, IL-10, and fractalkine concentrations were measured in serum and supernatants from cultured PBMCs. Anthropometric (BMI, WHR) and body composition measurements were taken using bioimpedance analysis (BIA) and dual-energy X-ray absorptiometry (DXA). Results and Conclusion: The schizophrenia patients demonstrated significantly higher levels of serum CXCL8 (schizophrenia: 13.4 ± 15.7 pg/mL, control: 6.9 ± 4.2 pg/mL, p = 0.001) and lower level of serum fractalkine (schizophrenia: 22.8 ± 9.9 pg/mL, control: 45.4 ± 84.5 pg/mL, p = 0.041). Serum IL-10 levels did not significantly differ. No in vitro synthesis of fractalkine was observed. Neither unstimulated or PHA-stimulated CXCL8 secretion differed between the two groups (p >0.05). The patients not taking mood stabilizers (MS-) demonstrated significantly higher CXCL8 levels than those on mood stabilizers (MS+) (p = 0.03) and control (p < 0.001). In addition, the MS- sub-group demonstrated significantly lower serum fraktalkine than controls (p = 0.009). These effects could be described as pseudo-normalization of CXCL8 and fractalkine in schizophrenia patients taking mood stabilizers.

The association between serum levels of TNF-α and IL-6 in schizophrenic patients and their metabolic status - A case control study.

INTRODUCTION AND OBJECTIVES: According to immunological theory of schizophrenia, dysfunctions of the immune system are linked with the pathology of schizophrenia. Among cytokines, tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) seem to be correlated with psychopathology of schizophrenia. Both IL-6 and TNF-α are produced in the fat tissue by adipocytes. Thus, cytokine levels in obese patients are increased compared with healthy subjects. These metabolic underlying mechanisms may be an important confounding factor in the studies on cytokines levels in schizophrenia. The aim of this study was to evaluate how metabolic alterations affect peripheral IL-6 and TNF-α levels in schizophrenia patients. MATERIALS AND METHODS: This was a case-control study, 30 schizophrenia patients were recruited in the study group and 30 healthy subjects were matched by sex and age. Serum levels of TNF-α and Il-6 were measured using ELISA test, together with detailed anthropometric, laboratory and body composition parameters (determined using bioelectric impedance analysis). RESULTS AND CONCLUSIONS: Serum TNF-α concentration in the schizophrenia group was 6.05 ± 1.61 ng/mL and 5.94 ± 1.26 ng/mL in the control group. The difference between these two groups was not significant (p = .79). Serum IL-6 concentration in the schizophrenia group was 1.54 ± 1.46 ng/mL and in the control group 1.39 ± 1.39 ng/mL. Again, the difference was not significant (p = .51). We have analysed the relationship between anthropometric and metabolic variables and serum IL-6 and TNF-α concentrations. In conclusion, TNF-α was more sensitive to metabolic alterations compared with IL-6. This observation may be beneficial for further research on immune system in schizophrenia, indicating that studies of IL-6 and TNF-α should be controlled at least for major metabolic parameters (BMI, WHR).

Does metabolic status affect serum levels of BDNF and MMP-9 in patients with schizophrenia?

The purpose of the article: Brain-derived neurotrophic factor (BDNF) and matrix metalloproteinase-9 (MMP-9) are involved in the processes of neurogenesis, synaptic plasticity, learning and memory. Growing number of studies shows a relationship between BDNF or MMP-9 and schizophrenia. Also, BDNF and MMP-9 levels may be affected by metabolic parameters, such as obesity or dyslipidemia. Our hypothesis is that alterations of BDNF or MMP-9 levels in schizophrenia might be secondary to metabolic abnormalities, often found among schizophrenia patients. Materials and methods: We have compared BDNF and MMP-9 between patients with schizophrenia (n = 64, age 49 ± 8.2 y) and healthy controls (n = 32, age 51 ± 8.9 y) in the context of cardio-metabolic parameters. Serum levels of BDNF and MMP-9 were measured using ELISA test, body composition parameters were determined using bioelectric impedance analysis. Results and conclusions: Our results showed significantly lowered serum BDNF concentration in the schizophrenia group (schizophrenia: 23.8 ± 7.83 ng/mL, control: 27.69 ± 8.11 ng/mL, p = 0.03). Serum MMP-9 concentration in schizophrenia group did not differ compared with the control group (schizophrenia: 456.8 ± 278.4 ng/mL, control: 341.5 ± 162.4 ng/mL, p = 0.07). After adjusting for age, all anthropometric parameters, body composition and laboratory tests BDNF were still significantly lower in the schizophrenia group. However, MMP-9 became significantly elevated in the schizophrenia group after adjusting for several anthropometric and body composition covariates. Our results confirmed reduced serum BDNF concentration in patients with schizophrenia. Also, this reduction seems to be independent of metabolic abnormalities. On the other hand, our hypothesis that MMP-9 level in schizophrenia is altered due to metabolic abnormalities might be true.

In schizophrenia serum level of neurotrophin-3 (NT-3) is increased only if depressive symptoms are present.

AIM: Neurotrophin-3 (NT-3) is a neurotrophic factor responsible for promoting development, survival and function of neurons. NT-3 may be involved in the etiopathology of schizophrenia and mood disorders. However it must be cleared up if changes of NT-3 level are associated with schizophrenia itself or are secondary to certain symptoms (e.g. negative or depressive). The aim of this study was to examine whether the presence of negative or depressive symptoms affects peripheral NT-3 concentration in patients with schizophrenia. METHODS: Data for 69 Caucasian adult hospitalized patients with chronic paranoid schizophrenia was compared with 27 healthy subjects. Level of NT-3 was measured in blood serum using enzyme-linked immunosorbent assay. Clinical symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS) and Calgary Depression Scale for Schizophrenia (CDSS). RESULTS: Patients were stratified into three sub-groups: non-depressed with no dominating negative symptoms (DEP-/NEG-), non-depressed with dominating negative symptoms (DEP-/NEG+) and depressed with dominating negative symptoms (DEP+/NEG+). Mean NT-3 concentration was higher in the DEP+/NEG + sub-group (202.61 ± 258.76 pg/mL) compared with the DEP-/NEG+ (83.79 ± 215.75 pg/mL), DEP-/NEG- (83.79 ± 215.75 pg/mL) and control (36.47 ± 73.84 pg/mL) sub-groups (p = 0.016). CONCLUSION: We found that in schizophrenia serum level of neurotrophin-3 (NT-3) is increased only if depressive symptoms are present. There was no difference in NT-3 level between schizophrenia patients and controls.

Neutrophil-lymphocyte ratio is increased in elderly patients with first episode depression, but not in recurrent depression.

Association between inflammation and depression, especially in elderly patients, leads to conclusions about their shared influence on risk of cardiovascular disease and death. It might be found useful to predict those issues by monitoring inflammatory parameters, such as neutrophil/lymphocyte ratio (NLR). The aim of this study was to determine the NLR in elderly patients with unipolar depression compared with non-depressed elderly patients. NLR was measured in 684 Caucasian subjects (depressed: n = 465, non-depressed: n = 219), aged ≥ 60 (depressed: mean age 74.8 ±â€¯7.8 years, non-depressed: mean age: 71.1 ±â€¯5.7 years). There were two subgroups within depressed patients: first episode depression (n = 138, 29.6%) and recurrent depression (n = 328, 70.3%). NLR was calculated as ratio between absolute neutrophil count to absolute lymphocyte count. NLR was significantly higher in unmedicated patients with depression compared with healthy control (2.10 ±â€¯2.13 vs. 2.01 ±â€¯0.75, p = 0.004). It was higher in first episode depression compared with recurrent depression (2.11 ±â€¯1.76 vs 1.64 ±â€¯1.04, p < 0.05). There was a positive correlation with severity of symptoms. We found non-specific effect of treatment with antidepressants or antipsychotics on lower NLR. Increased NLR in patients with first episode of depression compared to recurrent depression and healthy control may have important clinical consequences. Severity of symptoms are positively correlated with NLR, which may indicate that with increasing severity of depression, the risk of cardiovascular events is also rising, which leads to higher mortality. In elderly patients with depression even a small reduction of such risk may translate into better prognosis and improve quality of live. The difference between first episode and recurrent depression in terms of inflammatory biomarkers requires further studies.

Atherogenic Indices Are Increased in Elderly Patients with Unipolar Depression-Case-Control Analysis.

BACKGROUND: Blood lipids are widely used in monitoring the risk of cardiovascular diseases; however, atherogenic indices are more precise markers. The aim of the study was to determine differences in atherogenic indices in elderly patients with unipolar depression (DEP) compared with nondepressed elderly patients (nonDEP) using case-control analysis. METHODS: Fasting serum lipid profiles were measured in 564 (depressed: n = 282, nondepressed: n = 282, 83.7% (n = 236) women in both groups) Caucasian inpatients aged ≥60, with mean age 76.9 years. Patients from both groups were matched for age and sex. Atherogenic index of plasma (AIP) was calculated as log10(triglycerides/HDL cholesterol). Castelli atherogenic indices were calculated as follows: AILDL/HDL is the ratio of low-density lipoprotein (LDL) cholesterol to high-density lipoprotein (HDL) cholesterol and AITC/HDL is the ratio of total cholesterol to HDL cholesterol. RESULTS: HDL levels were significantly decreased in depressed patients (48.2 ± 14.4 mg/dL vs. 54.5 ± 17.7 mg/dL). No other differences in lipid profile were found. We found that all three analyzed atherogenic indices were increased in depressed patients (AIP: 0.41 ± 0.28 vs. 0.33 ± 0.27, AILDL/HDL: 2.90 ± 1.41 vs. 2.42 ± 1.07, AITC/HDL: 4.51 ± 1.84 vs. 3.79 ± 1.21). We found associations between depression severity and reduced level of HDL (ß = -0.02) or increased AIP (ß = 1.66). CONCLUSIONS: All three atherogenic indices were increased in elderly patients with depression. Since depression and age are associated with elevated risk of cardiovascular events, elderly patients with depression should be carefully monitored for abnormal lipid status to reduce their cardiovascular risk. The role of lipid abnormalities in the pathogenesis of depression requires further studies.