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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.

Myelin deficiency is commonly recognized as an important pathological feature of brain tissues in schizophrenia (SZ). In this pilot study, global myelin content abnormalities in white matter (WM) and gray matter (GM) of SZ patients were non-invasively investigated using a novel clinically-targeted quantitative myelin imaging technique, fast macromolecular proton fraction (MPF) mapping. MPF maps were obtained from 23 healthy subjects and 31 SZ patients using a clinical 1.5T magnetic resonance imaging (MRI) scanner. Mean MPF in WM and GM was compared between the healthy control subjects and SZ patients with positive and negative leading symptoms using the multivariate analysis of covariance. The SZ patients had significantly reduced MPF in GM (p < 0.001) and WM (p = 0.02) with the corresponding relative decrease of 5% and 3%, respectively. The effect sizes for the myelin content loss in SZ relative to the control group were 1.0 and 1.5 for WM and GM, respectively. The SZ patients with leading negative symptoms had significantly lower MPF in GM (p < 0.001) and WM (p = 0.003) as compared to the controls and showed a significant MPF decrease in WM (p = 0.03) relative to the patients with leading positive symptoms. MPF in WM significantly negatively correlated with the disease duration in SZ patients (Pearson’s r = −0.51; p = 0.004). This study demonstrates that chronic SZ is characterized by global microscopic brain hypomyelination of both WM and GM, which is associated with the disease duration and negative symptoms. Myelin deficiency in SZ can be detected and quantified by the fast MPF mapping method.

The life expectancy of patients with psychotic disorders is significantly shorter than that of the general population; antipsychotic-induced metabolic disorders play a significant role in reducing life expectancy. Both metabolic syndrome (MetS) and schizophrenia are multifactorial conditions. One area where the two conditions overlap is oxidative stress, which is present in both diseases. The glutathione-S-transferase (GST) system is a major line of defense against exogenous toxicants and oxidative damage to cells. The aim of our study was to perform an association analysis of gene polymorphisms with metabolic disorders in patients with schizophrenia treated with antipsychotic therapy. Methods: A total of 639 white patients with schizophrenia (ICD-10) from Siberia (Russia) were included in the study. Genotyping was carried out using real-time polymerase chain reaction for two single-nucleotide polymorphisms (SNPs) in the GSTP1 (rs614080 and rs1695) and one SNP in the GSTO1 (rs49252). Results: We found that rs1695*GG genotype of GSTP1 is a risk factor for the development of overweight (OR 2.36; 95% CI: 1.3–4.29; p = 0.0054). In the subgroup of patients receiving first-generation antipsychotics as basic therapy, the risk of overweight was associated with carriage of the rs1695*GG (OR 5.43; 95% CI: 2.24–13.16; p < 0.001) genotype of GSTP1 in a recessive model of inheritance. In contrast, an association of rs1695*G GSTP1 with obesity (OR: 0.42; 95% CI: 0.20–0.87; p = 0.018) was shown in the dominant model of inheritance in patients receiving second-generation antipsychotics. Conclusions: The pilot results obtained confirm the hypothesis of a violation of the antioxidant status, in particular the involvement of GSTP1, in the development of antipsychotic-induced metabolic disorders in schizophrenia. Further studies with larger samples and different ethnic groups are needed to confirm the obtained results.

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.

Background: Schizophrenia is a complex mental disorder with a high heritability. Dysfunction of the N-methyl-D-aspartate (NMDA)-type glutamate receptors may be involved in the pathogenesis of schizophrenia. In this study, we examined the contribution of GRIN2A and GRIN2B (Glutamate Ionotropic Receptor NMDA Type Subunit 2A/2B) polymorphisms to the clinical features of schizophrenia, such as the leading symptoms, the type of course, and the age of onset. Methods: A population of 402 Russian patients with schizophrenia from the Siberian region was investigated. Genotyping of seventeen single-nucleotide polymorphisms (SNPs) in GRIN2A and GRIN2B was performed using QuantStudio™ 3D Digital PCR System Life Technologies amplifier using TaqMan Validated SNP Genotyping Assay kits (Applied Biosystems). The results were analyzed using Chi-square and the Fisher’s exact tests. Results: We found an association of GRIN2A rs7206256 and rs11644461 and GRIN2B rs7313149 with the early onset (before the age of 18 years old) schizophrenia. We did not reveal any associations of GRIN2A and GRIN2B polymorphisms with leading (positive vs. negative) symptoms or type of course (continuous vs. episodic) of schizophrenia. Conclusions: In the study, we confirmed the involvement of the GRIN2A and GRIN2B genes in the early onset of schizophrenia in a Russian population of the Siberian region.

The level hydrolysis of myelin basic protein (MBP) by IgG in patients with schizophrenia was studied depending on the clinical features and course of the disease. The patients were grouped according to type of schizophrenia and type of disease course. We found that IgGs isolated and purified from sera of schizophrenia patients’ blood hydrolyses human MBP, and the level of this hydrolysis significantly exceeds that of healthy individuals. Detection of protease activity corresponding only to intact IgGs in polyacrylamide gel fragments, together with data of gel filtration of antibodies under conditions of “acid shock” (concordance of optical density profile of IgG with profile of MBP-hydrolyzing activity) and with the absence of any other proteins and bands in gradient SDS-PAGE and in PVDF membrane provides direct evidence that the IgGs from the schizophrenia patients have MBP-hydrolyzing activity. The antibodies-specific proteolytic activity of patients with acute schizophrenia (1.026 [0.205; 3.372] mg MBP/mg IgG/h) significantly exceeds the activity of IgG in patients in remission (0.656 [0.279; 0.873] mg MBP/mg IgG/h) and in healthy individuals (0.000 [0.00; 0.367] mg MBP/mg IgG/h). When comparing the specific activity in patients with different types of disease course, we have found that patients with a continuous course of paranoid schizophrenia (1.810 [0.746; 4.101 mg MBP/mg IgG/h]) had maximal activity values. It can be assumed that the increase in the activity of MBP-hydrolyzing antibodies is due to the activation of humoral immunity in acute schizophrenia.

Machine learning and artificial intelligence technologies are known to be a convenient tool for analyzing multi-domain data in precision psychiatry. In the case of schizophrenia, the most commonly used data sources for such purposes are neuroimaging, voice and language patterns, and mobile phone data. Data on peripheral markers can also be useful for building predictive models. Here, we have developed five predictive models for the binary classification of schizophrenia patients and healthy individuals. Data on serum concentrations of cytokines, chemokines, growth factors, and age were among 38 parameters used to build these models. The sample consisted of 217 schizophrenia patients and 90 healthy individuals. The models architecture was involved logistic regression, deep neural networks, decision trees, support vector machine, and k-nearest neighbors algorithms. It was shown that the algorithm based on a deep neural network (consisting of five layers) showed a slightly higher sensitivity (0.87 ± 0.04) and specificity (0.52 ± 0.06) than other algorithms. Combining all variables into a single classifier showed a cumulative effect that exceeded the effectiveness of individual variables, indicating the need to use multiple biomarkers to diagnose schizophrenia. Thus, the data obtained showed the promise of using data on peripheral biomarkers and machine learning methods for diagnosing schizophrenia.

Both dehydroepiandrosterone (DHEAS) and cortisol are secreted by the adrenal glands and may modulate metabolic syndrome (MetS), which often affects the health of patients with schizophrenia. The relationship between the serum levels of these hormones and MetS has not been established. In this pilot study, we investigated the serum levels in schizophrenia patients with and without MetS and compared them with those in healthy volunteers. After obtaining informed consent, 110 patients with acute paranoid schizophrenia were recruited directly after admission to the Mental Health Research Institute. The control group consisted of 51 persons reported on questioning to be mentally and somatically healthy. Blood samples to prepare serum were drawn after an 8-h overnight fast during one of the first days of admission. Serum cortisol and DHEAS concentrations were quantified by enzyme-linked immunosorbent assay. A total of 42 patients had MetS and 68 patients were without MetS. The cortisol blood level was significantly (p = 0.012) higher in schizophrenia patients without MetS in comparison to healthy controls, while patients with schizophrenia and a MetS have significantly (p = 0.014) lower DHEAS levels than healthy volunteers. These differences could, however, exclusively be attributed to female participants. Analysis of covariance adjusted for gender and age demonstrated a significant relationship between age and DHEAS levels (F = 9.512, р = 0.003). Lower DHEAS serum levels in relationship to MetS become evident in women, but not in men, and have age differences as a confounding factor.

Several studies have shown that patients with schizophrenia are at high risk for metabolic syndrome (MetS) and bioenergetic dysfunction. Because acylcarnitines are involved in bioenergetic pathways and reflect the functioning of mitochondria, we hypothesized that these compounds are biomarkers of MetS in schizophrenia. The aim of this work was to quantify acylcarnitines and branched-chain amino acids in patients with schizophrenia comorbid with MetS. The study included 112 patients with paranoid schizophrenia treated with antipsychotics. Among them, 39 subjects met criteria of MetS. Concentrations of 30 acylcarnitines and three amino acids in dry serum spots were measured by liquid chromatography coupled with tandem mass spectrometry. MetS patients were found to have higher levels of valeryl carnitine (C5), leucine/isoleucine, and alanine as compared with patients without MetS, indicating possible participation of these compounds in the pathogenesis of metabolic disorders in schizophrenia. In patients with paranoid schizophrenia with or without MetS, lower levels of carnitines C10, C10:1, C12, and C18 were recorded as compared with the healthy individuals (n = 70), implying deterioration of energy metabolism. We believe that this finding can be explained by effects of antipsychotic medication on an enzyme called carnitine-palmitoyl transferase I.

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.