Alterations in a variety of immune parameters, including abnormal cytokine levels, are known to be found in schizophrenia. These changes can be useful in identifying patients with the most severe immune abnormalities.

To develop approaches to stratification of schizophrenia patients based on cytokine levels using cluster analysis.

We recruited 53 patients (25 women/28 men) with a verified diagnosis of simple or paranoid schizophrenia and 37 healthy individuals (19 women/18 men) in our study. Serum levels of IL-1β, IL-2, IL-4, IL-6, TNFα, INFα, BAFF, GM-CSF, NGFβ, NRG1, and GDNF were determined using a MAGPIX multiplex analyzer (Luminex, USA). Statistical analysis was performed in Statistica 10.

Principal component analysis and partial least-squares discriminant analysis showed that the combined multi-cytokine profiles of the studied groups differ. The results of the k-means cluster analysis are presented in Table 1 The most reliable results are obtained by a combination of 4 variable: IL-1β, IL- 4, BAFF and GDNF. Table 1 Percent of individuals classified in different clusters depending of number of parameters using for classification.

A subgroup (сluster 1) of schizophrenic patients with severe immune abnormalities was identified using data on the levels of IL-1β, IL-4, BAFF and GDNF. Anti-inflammatory therapy is recommended for this subgroup of patients. Support by Grant of RSF № 21-75-00102.

No significant relationships.

Inflammation and immune dysregulation could contribute to the pathogenesis of schizophrenia. Osteopontin (OPN) is a key cytokine-like molecule in cellular immune response and it can directly modulate the cytokine expression and survival of microglia. Furthermore, its mRNA expression is elevated in first episode psychosis. Imbalance of T-helper subtypes could also represent a vulnerability factor for schizophrenia.

The aim of this study was to evaluate the relevance of T-helper subtype associated cytokines, OPN and NLR in the assessment of the severity of schizophrenia.

22 patients with schizophrenia were assessed for the intensity of their symptoms by PANSS and CGI scores. Serum OPN, IFNy, IL-10 and IL-8 concentrations were measured by ELISA kits and NLR was calculated from blood count. Statistical evaluation was performed using Mann-Whitney U test, Student’s t test and Spearman correlation.

We found significant correlation between the level of OPN and PANSS-total, PANSS-general scores. IFNy level and NLR showed significant correlation with PANSS-total, PANSS-positive, PANSS-general and CGI score. Antipsychotic therapy only had significant effects on NLR and OPN levels, both of which were significantly reduced after long-term antipsychotic treatment.

Our results indicate that elevated OPN and IFNy concentrations, and increased NLR are associated with severe symptoms in schizophrenia and suggest the importance of Th1 subtype in patients with high PANSS-positive and PANSS-general score. Antipsychotic treatment had significant effects on the level of OPN and NLR, but not on the level of IFNy. Overall our results strengthen the inflammation hypothesis of schizophrenia.

No significant relationships.

The question of the involvement of inflammatory and autoimmune processes in schizophrenia pathogenesis has become the most relevant in the last decade and yet is not fully understood.

The study included 60 patients with paranoid schizophrenia (age 18 - 55 y.o.) and 30 healthy control group participants. Patients were in a stabilization state without a history of organic brain disorder or another verified somatic disease in the exacerbation phase.

Research methods included follow-up method, neuropsychological (PANSS, BAC-S), laboratory (enzyme immunoassay, flow cytometry), and statistical.

Patients with schizophrenia had significant structural disorders of thinking, passive, apathetic withdrawal, negativism, impaired attention, psychomotor speed, volitional impulses. Cognitive impairment was detected in all study participants. Severe impairments are noted in the executive functioning, hand-eye coordination, attention, psychomotor speed. The severity of cognitive impairments correlated with the severity of clinical symptoms. Patients with schizophrenia had a significant decrease in central memory T-regulators levels, and an increase in Th1 and Th2 subsets, «double-positive» and «сlassic» Th17, Tfh2, «classic» Tfh17, and in Tfh17.1 (Pic.1).

Picture. 1. T-helper subsets in patients with schizophrenia. They also had high levels of CCL20, IL-10, IL-12, IL-1β, IL-27, IL-31, IL-4, IL-13, IL-6, IL-9, TNFα in comparison with a control group. A significantly decreased levels of IL-17A, IL-17F, IL-2, IL-22, and TNFβ were also described in this group of patients.

Patients with schizophrenia may be characterized by the presence of an inflammatory process and a high chance of autoimmunity. Aknowledgement. This work was supported by the grant of the Russian Federation Government, contract 14.W03.31.0009

No significant relationships.

According to current knowledge inflammation seems to be strongly associated with pathogenesis of schizophrenia. Multiple studies and meta-analyses showed increased levels of inflammatory markers in plasma of schizophrenia patients. Individual studies have shown a relationship between the levels of inflammatory markers and the presence of deficit syndrome, but their results are inconsistent.

Analysis of associations between inflammatory markers and the presence of deficit syndrome in schizophrenia.

Studied group consisted of 50 patients with diagnosed schizophrenia (F20) for at least 10 years, including 14 patients with deficit schizophrenia (DS) and 36 patients with non-deficit schizophrenia (NDS). DS and NDS did not differ significantly in age, BMI, duration of schizophrenia, types and doses of antipsychotics (chlorpromazine equivalent), but differed in sex (x2=4.28,p=0.039). Concentrations of inflammatory markers i.e. IL-6,IL-8,IL-10,TNFα,IFNγ,CRP were measured in serum using sensitive ELISA assays.

Initial analysis showed significantly lower concentration of IL-8 in DS compared to NDS (t=-3.18,p=0.002). This association remain significant (F=7.63,p=0.0085) after co-varying for age, sex, BMI, duration of schizophrenia, type of antipsychotic medications and antipsychotics doses. Multiple logistic regression showed that female gender (OR=0.18 [0.04-0.87],p=0.034) and higher IL-8 concentrations (OR=0.03 [0.002-0.39],p=0.007) are independent predictors of lower odds of having DS.

Low IL-8 concentrations seem to be promising predictor of the presence of DS in schizophrenia patients, but results need further investigations. The research was funded by Polish Minister of Science and Higher Education’s program named “Regional Initiative of Excellence” in 2019–2022, grant number 002/RID/2018/2019 to the amount of 12000000PLN and by National Science Centre, Poland (2019/03/X/NZ5/00719)

No significant relationships.

Evidence has demonstrated associations of bipolar disorder (BD) with cognitive impairment, dysregulated proinflammatory cytokines, and appetite hormones.

To compare executive dysfunction, proinflammatory cytokines, and appetite hormones between patients with first-episode and multiple-episode BDs.

This cross-sectional study included young adults aged 18 to 39 years who were diagnosed as having type 1 BD in the first or recurrent episode and a group of age-/sex-matched healthy controls. Data regarding patient characteristics, clinical symptoms, cytokines (C-reactive protein [CRP], interleukin-6, and tumor necrosis factor [TNF]-α), appetite hormones (leptin, adiponectin, ghrelin, and insulin), and executive function evaluated using the Wisconsin Card Sorting Test (WCST) were collected.

A total of 112 participants (38 patients in the multiple-episode BD group, 31 patients in the first-episode BD group, and 43 in the control group) were included. Multivariate analysis revealed that patients in the multiple-episode BD group performed significantly worse in the WCST (P < .05) and had higher levels of ghrelin (P = .002), and lower levels of CRP (P = .040) than those in the first-episode BD group. Patients with BD had significantly higher TNF-α and ghrelin levels compared with the healthy controls. No significant associations of CRP, TNF-α, and ghrelin levels with executive function were observed.

Profiles in proinflammatory cytokines and appetite hormones as well as executive function significantly differed between patients with first-episode and multiple-episode BDs and controls, which may suggest their potential roles in the clinical stages and pathophysiology of type 1 BD.

This study aimed to elucidate whether molecular signalling involved in upper airway remodelling is enhanced in patients with obstructive sleep apnoea.

Twenty patients with mild obstructive sleep apnoea (control group) and 40 patients with moderate to severe obstructive sleep apnoea (obstructive sleep apnoea group) who desired uvulopalatopharyngoplasty were recruited for the study. After uvulopalatopharyngoplasty, surgical specimens of the uvula were subjected to haematoxylin and eosin, Masson's trichrome and immunohistochemical staining. Western blot and reverse transcriptase-polymerase chain reaction were used to evaluate the protein and messenger RNA expressions.

The obstructive sleep apnoea group showed more severe inflammation, increased collagen deposition and higher immunohistochemical staining intensity for TGF-ß and MMP-9 as well as higher protein and messenger RNA expression of MMP-9, VEGF, TGF-ß, p38 MAPK, SMAD 2/3, AKT and JNK in the uvula than control group.

Patients with obstructive sleep apnoea demonstrated more severe inflammation, increased airway remodelling, and increased protein and messenger RNA expression of pro-inflammatory and pro-fibrotic cytokines in the uvula than control participants.

Dysregulated proinflammatory cytokines have been shown to be associated with suicidal behavior. Cognitive deficits in working memory and inhibitory control have been demonstrated in depressed patients and people with suicidal ideation (SI). However, the association between proinflammatory cytokines, SI, and cognitive deficits in patients with major depressive disorder (MDD) remains unclear.

A total of 77 patients with MDD and age-/sex-matched 60 healthy individuals were recruited. MDD patients were divided into two groups: with SI (n = 36) and no SI (n = 41). SI was defined by a score of ≥2 in item 3 of the 17-item Hamilton Rating Scale for Depression. Levels of proinflammatory cytokines, including soluble interleukin-6 receptor, soluble tumor necrosis factor-α receptor type 1, and C-reactive protein (CRP), were measured, and cognitive function was assessed using 2-back task and Go/No-Go task.

Patients with SI had higher levels of CRP than those without SI and controls (P = .007). CRP was positively associated with SI (β = 0.21, P = .037), independent of cognitive function and depressive symptoms. Furthermore, SI was associated with cognitive deficits in working memory and inhibitory control after adjusting for confounding factors (P < .05).

Our findings suggest that higher levels of serum CRP and deficits in working memory and inhibitory control may be associated with higher SI among patients with MDD.

Bipolar Disorder (BD) is a severe recurrent disorder with a complex biogenetic and psychosocial etiology. The immune system cytokines in interaction with the CNS play a role in the pathophysiology.

To compare inflammatory cytokines between BD patients and controls during the manic episode; additionally, compare these cytokines with psychiatric symptoms and cognitive performance during follow-up.

We recruited 25 BD patients in mania with paired controls. We measured baseline IL-2, IL-4, IL-8, IL-10, GM-CSG, TNF- α, and TNF- γ in plasma. We used U-Mann-Whitney for group comparison and Spearman correlation between sub-group follow-up assessments and cytokines.

We found a significant difference in IL-6 between subjects and controls (figure 1). During the follow-up, we found a correlation with psychiatric symptoms, cognition, and cytokines during manic episodes (Table 1). Table 1. Follow-up Correlation with cytokines during a manic episode.

(+): positive correlation; (-): negative correlation. WMT: working-memory test, PST: Processing-speed test.

IL-6 was significantly different in patients with BD during a manic episode regardless of the treatment they were taking. IL-10 at manic episode was negatively correlated to general psychiatric symptoms, IL-4 positive correlated to depressive symptoms, and cognitive performance was positively correlated to TNF- α and TNF- γ at follow-up.

No significant relationships.

A growing body of evidence in both chronic and first-episode schizophrenia report increased expression of pro-inflammatory substances in the blood and cerebrospinal fluid of patients. However, there is not much data in the literature on immune alterations in unaffected first-degree relatives (FDRs) of the patients.

We aimed to evaluate inflammatory aberrancies in patients with schizophrenia, their unaffected first-degree relatives (FDRs) and healthy controls.

50 chronic, stable schizophrenia patients, 42 FDRs and 40 healthy subjects with no family history (HCSs) were recruited to the study. IL-1β, IL-6, TNF-a and CRP levels were measured. Complete blood counts, fasting glucose and lipid levels were analyzed and neutrofil-lymohocyte ratio (NLR) were calculated.

There was a significant group difference in all cytokine levels after controlling for age, gender, smoking status, comorbid medical diseases, BMI and blood glucose and tyrigliseride levels (p<.001). FDRs showed significantly higher serum levels of cytokines than HCs, in the same way as the corresponding schizophrenia patients but a lower level. Pairwaise comparisions revealed that the differences were significant between each group after controlling for confounders (p<.001 for all comparisons). However, NLR and CRP levels were not different between groups.

Our results support the role of inflammatory aberrancies in the pathophysiology of schizophrenia. The finding of abnormal cytokine levels both in schizophrenic patients and FDRs indicates that such immunological alterations are not exclusive to the patients and can be possible endophenotypes for the disorder.

No significant relationships.

In the scientific world widely discussed phenomenon of “cytokine-induced depression”. Macrophages have high plasticity and are able to control the inflammatory response; in particular, anti-inflammatory type-2 macrophages have a pronounced potential due to complex soluble factors production.

We have developed an original method for the type-2 macrophages generation; the resulting macrophages are characterized by the high level of a whole range of neurotrophic, neuroprotective, proangiogenic and anti-inflammatory factors production. The aim of the study was to investigate effects of human type-2 macrophages soluble products on behavioral phenotype and brain cytokines synthesis in depressive-like animals.

Type-2 macrophages were generated by culturing an adherent fraction of mononuclear cells with 50 ng/ml recombinant human GM-CSF in serum deprivation conditions for 7 days. (CBA x C57Bl/6)F1 depressive-like male mice, developed under the long-term social stress, were undergoing the human type-2 macrophages conditioned medium intranasal administration (60 ml twice daily for one animal) for 6 days. Mice behavioral phenotyping was carried out using an automatic registration system (Noldus Information Technology). Cytokines were determined by ELISA.

Depressive-like mice behavioral phenotyping after type-2 macrophages conditioned medium administration revealed anhedonia decrease, motor activity stimulation in the open field and forced swimming tests, anxiety reduction in elevated plus maze. Behavioral changes were recorded against the pro-inflammatory cytokines (TNF-α, IL-1β, IL- 6, INFγ) decrease in striatum and hippocampus, as well as anti-inflammatory IL- 10 increase in hippocampus and hypothalamus.

Results demonstrated the effectiveness of human type-2 macrophages biologically active soluble products in relation to the stress-induced depressive-like behavior editing

No significant relationships.

Several studies have shown impaired cytokine status in both patients with depression and chronic heart failure (HF).

to study the effect of vortioxetine on the level of pro-inflammatory cytokines: interleukin -1β (IL-1β) and interleukin - 6 (IL-6).

there were examined 80 patients with HF with reduced ejection fraction (HFrEF) of ischemic genesis with functional class (FC) II-III (NYHA), 37 patients were without depression, 43 - with mild or moderate depressive disorders. Those with mild or moderate depressive disorders were divided into 2 subgroups: 21 patients received psychotherapy, 22 patients, in addition to psychotherapy, were prescribed vortioxetine at a dose of 10 mg / day in the morning after meals. The control group consisted of 20 healthy individuals. The level of cytokines in the blood was determined by ELISA method.

Patients with CHF have an increase in levels of pro-inflammatory cytokines. Thus, the concentration in the serum of IL-1β was 2.3 times higher than the same indicator in the control group: (56.45 ± 4.17) pg / ml, against (24.71 ± 4.21) pg / ml p <0.001). Depression caused an additional increase in the levels of IL-1β by 13.5% (p <0.05) and IL-6 - by 17.3% (p <0.01). Additional administration of vortioxetine caused a more rapid decrease in blood levels of both IL-1β (HR 0.87 [95% CI 0.72-0.97; p = 0.034]) and IL-6 (HR 0.81 [95% CI 0.68-0.93; p = 0.029]).

Thus, vortioxetine causes a decrease in the concentration of pro-inflammatory cytokines IL-1β and IL-6 in patients with HF and comorbid depression.

No significant relationships.