Chemokines are known to be immunoregulatory proteins involved not only in lymphocyte chemotaxis to the site of inflammation, but also in neuromodulation, neurogenesis, and neurotransmission. Multiple lines of evidence suggest a peripheral proinflammatory state and neuroinflammation in at least a third of patients with schizophrenia. Therefore, chemokines can be active players in these processes. In this systematic review, we analyzed the available data on chemokine dysregulation in schizophrenia and the association of chemokines with neuroinflammation. It has been shown that there is a genetic association of chemokine and chemokine receptor gene polymorphisms in schizophrenia. Besides, the most reliable data confirmed by the results of meta-analyses showed an increase in CXCL8/IL-8, CCL2/MCP-1, CCL4/MIP-1β, CCL11/eotaxin-1 in the blood of patients with schizophrenia. An increase in CXCL8 has been found in cerebrospinal fluid, but other chemokines have been less well studied. Increased/decreased expression of genes of chemokine and their receptors have been found in different areas of the brain and peripheral immune cells. The peripheral proinflammatory state may influence the expression of chemokines since their expression is regulated by pro- and anti-inflammatory cytokines. Mouse models have shown an association of schizophrenia with dysregulation of the CX3CL1-CX3CR1 and CXCL12-CXCR4 axes. Altogether, dysregulation in chemokine expression may contribute to neuroinflammation in schizophrenia. In conclusion, this evidence indicates the involvement of chemokines in the neurobiological processes associated with schizophrenia.

Schizophrenia is associated with a lowered life expectancy due to cardiovascular disease. This is, at least in part, related to an increased vulnerability to the development of metabolic syndrome (MetS) in patients with schizophrenia. The dysregulation of apolipoproteins (Apos) may also play a role in the pathogenesis of schizophrenia via their effect on cerebral cholesterol processing. The aim of this study was to investigate serum Apos A1, C3, E, A2 and C2 concentration in schizophrenia patients with or without MetS in comparison to healthy donors. After obtaining informed consent, 53 patients with a diagnosis of paranoid schizophrenia according to ICD-10 criteria (F20) were included. Patients were divided into two groups with (N = 26) and without (N = 27) MetS according to the criteria of the International Diabetes Federation. The control group included 20 mentally and physically healthy subjects. Serum Apos A1, A2, C2, C3 and E were measured using xMAP technology (Luminex). Serum ApoA1 was significantly decreased in patients with schizophrenia compared to healthy subjects (p = 0.002); ApoA2 was lower in patients without MetS in comparison to patients with MetS (p = 0.017) and the levels of ApoC3 and ApoC2 were increased in patients with schizophrenia with MetS in comparison with the control group and also with patients without MetS. No other significant differences were established concerning the other assayed apolipoproteins. In line with literature data the results of our study suggest that while disturbances in ApoA1 level may play a role in the pathogenesis of schizophrenia, ApoA2, ApoC2, ApoC3 and ApoE may be primarily related to metabolic imbalance.

The adipokines leptin, adiponectin, tumor necrosis factor-alpha (TNF-α), and interleukin 6 (IL-6) might be associated with metabolic syndrome (MetS) in patients with schizophrenia. In the present study, we attempted to confirm the results of previous reports and assessed their MetS-related correlation with body fat composition and biochemical parameters. We measured in 46 patients with schizophrenia and MetS serum levels of adiponectin insulin, leptin, TNF-α and IL-6 and compared these levels to those of patients with schizophrenia without MetS. The MetS patients had significantly increased leptin levels and leptin/adiponectin ratios, as well as decreased adiponectin levels. Leptin levels correlated with several metabolic parameters, both in patients with and without MetS, including body fat percentage, total fat fold, and body mass index (BMI). Patients without abnormal MetS components had lower levels of leptin and leptin/adiponectin ratios compared with patients who had one or two MetS components. Leptin/adiponectin ratios were higher in patients who had four rather than three MetS components. Multiple regression analysis revealed multiple associations for leptin but only one for adiponectin, TNF-α, and IL-6. Our results support an important pathophysiological role for leptin more than adiponectin in patients with schizophrenia with MetS.

Immune activation plays a major role in the pathogenesis of schizophrenia, as confirmed by many studies, systematic reviews, and meta-analyses. The important role of neuroinflammation in the formation of the relation between impaired neurobiological processes and schizophrenia psychopathology is being actively discussed. We quantified serum concentrations of 22 cytokines in 236 patients with schizophrenia and 103 mentally and somatically healthy individuals by a multiplex assay. We found higher TGF-α (p = 0.014), IFN-γ (p = 0.036), IL-5 (p < 0.001), IL-6 (p = 0.047), IL-8 (p = 0.005), IL-10 (p <0.001), IL-15 (p = 0.007), IL-1RA (p = 0.007), and TNF-α (p < 0.001) levels in patients with schizophrenia than in healthy individuals. Subgroup analysis revealed a much greater number of statistically significant differences in cytokine levels among females than among males. Patients with a continuous course of schizophrenia showed statistically significantly higher levels of IL-12p70 (p = 0.019), IL-1α (p = 0.046), and IL-1β (p = 0.035) compared with patients with an episodic course. Most cytokines were positively correlated with positive, general, and total PANSS scores. In patients with a duration of schizophrenia of 10 years or more, the level of IL-10 was higher than that in patients with a disease duration of 5 years or less (p = 0.042). Thus, an imbalance in cytokines was revealed in patients with schizophrenia, depending on sex and clinical characteristics of the disease.

The present study aims at comparing the change in cytokine levels in schizophrenia patients treated with atypical antipsychotics, with or without metabolic syndrome (MetS). The study included 101 patients with schizophrenia, 38 with and 63 without MetS, who received risperidone, quetiapine, olanzapine or aripiprazole for six weeks. We analyzed the concentration of 21 cytokines in the serum patients. The treatment with atypical antipsychotics changed some proinflammatory cytokine levels. It led to increased IFN-α2 (p = 0.010), IL-1α (p = 0.024) and IL-7 (p = 0.017) levels in patients with MetS, whereas the same treatment led to decreased levels of IFN-γ (p = 0.011), IL-1β (p = 0.035), IL-12р40 (p = 0.011), IL-17A (p = 0.031), IL-6 (p = 0.043) and TNF-α (p = 0.012) in individuals without MetS. Our results demonstrated the effects of atypical antipsychotics on the immune–inflammatory parameters, depending on the metabolic disturbances in schizophrenia patients.

Amino acids and acylcarnitines play an important role as substrates and intermediate products in most of pathways involved in schizophrenia development such as mitochondrial dysfunction, inflammation, lipid oxidation, DNA damage, oxidative stress, and apoptosis. It seems relevant to use an integrated approach with ‘omics’ technology to study their contribution. The aim of our study was to investigate serum amino acid and acylcarnitine levels in antipsychotics-treated patients with chronic schizophrenia compared with healthy donors. We measured serum levels of 15 amino acids and 30 acylcarnitines in 37 patients with schizophrenia and 36 healthy donors by means of tandem mass spectrometry. In summary, patients with chronic schizophrenia had an altered concentration of a few amino acids and acylcarnitines in comparison to the healthy probands. Further research is needed to assess and understand the identified changes.