Serum Growth Factors in Schizophrenia Patients.

Some hypotheses include schizophrenia as a neurodevelopmental disorder, which indicates a special role in growth factors and neuroglia in the development of schizophrenia symptoms. Growth factors are cytokine molecules that play an important role in the regulation of tissue nucleation, cell development, survival, and migration of all tissues in organisms, including the brain and nervous system. The aim of the study was to determine the serum concentration of six growth factors (EGF, VEGF, FGF-2, TGF-α, PDGF-AA, PDGF-AB/BB) in schizophrenia patients and to identify the correlations with clinical characteristics. After signing an informed consent form, 236 schizophrenia patients (F20 according to the ICD-10) and 102 healthy people were recruited in the study. In patients with schizophrenia, we observed a significant elevation in the TGF-α and PDGF-AA serum levels. The duration of schizophrenia was significantly positively correlated with the FGF-2 level. The PANSS total score had a positive correlation with the FGF-2 level and a negative correlation with the TGF-α level. Our results and literature indicate the involvement of growth factors in the mechanisms of development of schizophrenia. Combined biomarker screening seems to be necessary to improve diagnosis and clinical follow-up of patients with severe mental illnesses.

Hormones, oxidized proteins, and lipids in alcoholism. Duration of remission.

The instability of remission in alcohol dependence (AD) creates a need to search for criteria for predicting its duration. The aim of study was to determine the hormones, oxidized proteins, and lipids in patients with AD, and the possible relations between these parameters and the duration of remission. Blood samples were obtained from 49 male patients with AD after alcohol detoxification (Total group). Two groups of patients were formed: with unstable therapeutic remission up to 6 months (UTR-group); with stable therapeutic remission which lasted 12 months or longer (STR-group). The control group comprised men without AD. The levels of carbonylated proteins (CP), lipid peroxidation (TBA-RS) were determined in the blood plasma. The levels of cortisol, testosterone total, thyroid-stimulating hormone (TSH), triiodothyronine free (fT3), and thyroxine free (fT4) in the blood serum were measured. The Total group of patients showed an increase in CP, TBA-RS, Cortisol, cortisol/testosterone ratio, and a decrease in TSH, fT3, and fT3/fT4 levels. A set of parameters (T, fT3, fT4, cortisol/testosterone ratio) associated with unstable remission was identified.

Influence of eight ABCB1 polymorphisms on antidepressant response in a prospective cohort of treatment-free Russian patients with moderate or severe depression: An explorative psychopharmacological study with naturalistic design.

BACKGROUND: Many antidepressants are substrates of P-glycoprotein, an efflux transporter in the blood-brain-barrier encoded by the ABCB1 gene. Genetic variations might influence the transport rate of antidepressants and hence their pharmacological effects. This study investigates the influence of eight polymorphisms in the ABCB1 gene on antidepressant treatment response. METHOD: 152 patients were included from psychiatric departments of the Mental Health Research Institute in Tomsk. The difference in Hamilton-Depression-Rating-Scale (HAMD-17)-scores between baseline and week two, week two and four, and baseline and week four was used to estimate timing of improvement of depression. Associations between the ABCB1 gene-polymorphisms and reduction in HAMD-17 score were assessed using independent t-test and multiple linear regression. RESULTS: Tricyclic antidepressants were associated with a higher reduction of HAMD-17 score when compared to SSRIs. The SNP rs2235040 A-allele had a significant positive influence on the ΔHAMD-17(0→2W) score but a significant negative influence on the ΔHAMD-17(2→4W) score. The rs4148739 G-allele had a significant negative influence on the ΔHAMD-17(0→2W) score but a significant positive influence on the ΔHAMD-17(2→4W) score. The SNP rs2235015 T-allele is significant negatively related to the ΔHAMD-17(2→4W) score. CONCLUSION: ABCB1 Genetic variations appear to affect speed but not magnitude of antidepressant drug response.

Genetic polymorphisms of PIP5K2A and course of schizophrenia.

BACKGROUND: Schizophrenia is a severe highly heritable mental disorder. The clinical heterogeneity of schizophrenia is expressed in the difference in the leading symptoms and course of the disease. Identifying the genetic variants that affect clinical heterogeneity may ultimately reveal the genetic basis of the features of schizophrenia and suggest novel treatment targets. PIP5K2A (Phosphatidylinositol-4-Phosphate 5-Kinase Type II Alpha) has been investigated as a potential susceptibility gene for schizophrenia. METHODS: In this work, we studied the possible association between eleven polymorphic variants of PIP5K2A and the clinical features of schizophrenia in a population of 384 white Siberian patients with schizophrenia. Genotyping was carried out on QuantStudio 5 Real-Time PCR System with a TaqMan Validate SNP Genotyping Assay (Applied Biosystems, USA). RESULTS: PIP5K2A rs8341 (χ2 = 6.559, p = 0.038) and rs946961 (χ2 = 5.976, p = 0.049) showed significant association with course of schizophrenia (continuous or episodic). The rs8341*CT (OR = 1.63, 95% CI: 1.04-2.54) and rs946961*CC (OR = 5.17, 95% CI: 1.20-22.21) genotypes were associated with a continuous type of course, while the rs8341*TT genotype (OR = 0.53, 95% CI: 0.29-0.97) was associated with an episodic type of course of schizophrenia. Therefore rs8341*TT genotype presumably has protective effect against the more severe continuous course of schizophrenia compared to the episodic one. CONCLUSIONS: Our experimental data confirm that PIP5K2A is a genetic factor influencing the type of course of schizophrenia in Siberian population. Disturbances in the phosphatidylinositol pathways may be a possible reason for the transition to a more severe continuous course of schizophrenia.

Association between 8 P-glycoprotein (MDR1/ABCB1) gene polymorphisms and antipsychotic drug-induced hyperprolactinaemia.

INTRODUCTION: Hyperprolactinaemia, a common adverse effect of antipsychotic drugs, is primarily linked to blockade of dopamine D2 receptors in the pituitary gland. Certain antipsychotic drugs, such as, for example risperidone and paliperidone, are more likely to induce hyperprolactinaemia compared to others. This effect is probably caused by a relatively high blood/brain concentration ratio, a consequence of being a substrate of P-glycoprotein. Genetic variants of P-glycoprotein with changed functional activity might influence the potential of risperidone and paliperidone to cause hyperprolactinaemia as the altered blood/brain concentration ratio would lead to a reduced therapeutic drug level within essential brain areas making dose adaptations necessary. This increases exposure of dopamine D2 receptors within the pituitary gland. AIMS: To investigate possible associations between MDR1/ABCB1 gene polymorphisms and antipsychotic drug-induced hyperprolactinaemia in Russian patients with schizophrenia and to determine possible differences between risperidone/paliperidone and other antipsychotics. METHODS: In total, 446 patients with schizophrenia were included from 3 psychiatric hospitals in Siberia. Blood samples were obtained in a cross-sectional study design for DNA extraction and prolactin measurement. Associations between hyperprolactinaemia and 8 MDR1/ABCB1 gene-polymorphisms were assessed using logistic regression analysis accounting for covariates. The analysis was repeated in a patient subgroup using risperidone or paliperidone. RESULTS: We did not observe an association between any of the 8 single nucleotide polymorphisms and the prevalence of antipsychotic-induced hyperprolactinaemia in the total patient population. However, in the risperidone/paliperidone subgroup, the single nucleotide polymorphism rs2032582 (G2677T) was found to be negatively associated with risperidone/paliperidone-induced hyperprolactinaemia. CONCLUSION: This study revealed a significant association between the ABCB1 gene polymorphism rs2032582 (G2677T) and risperidone/paliperidone-induced hyperprolactinaemia.

Association of ANKK1 polymorphism with antipsychotic-induced hyperprolactinemia.

OBJECTIVE: Schizophrenia is a severe highly heritable mental disorder. Genetic polymorphisms of dopaminergic pathways are related to pathogenesis of drug response. Hyperprolactinemia (HPRL), a common adverse effect of antipsychotics, is attributed to blockade of dopamine D2 receptors. Ankyrin Repeat and Kinase Domain containing 1 (ANKK1) gene is closely related to Dopamine Receptor D2 type (DRD2) gene functioning. We examined whether the functional polymorphism rs2734849 in the ANKK1 gene is associated with antipsychotic-induced HPRL. METHODS: We recruited 446 patients with schizophrenia from among the Russian population of the Siberian region. The polymorphism rs2734849 in the ANKK1 gene was genotyped with The MassARRAY® Analyzer 4 by Agena Bioscience™, using the kit SEQUENOM Consumables iPLEXGold 384. Genotype and allele frequencies were compared between groups of schizophrenia patients with and without HPRL using the χ2 test. RESULTS: A comparison between schizophrenia patients with and without HPRL revealed significantly higher frequency of the C allele of the polymorphic variant rs2734849 in the ANKK1 gene in patients with HPRL as compared to the patients without it (χ2 = 3.70; p = .05; odds ratio [OR] = 1.30 [0.99-1.69]). CONCLUSION: The functional polymorphism rs2734849 in the ANKK1 gene was associated with HPRL in patients with schizophrenia.

Autoimmunity and immune system dysregulation in schizophrenia: IgGs from sera of patients hydrolyze myelin basic protein.

Several different theories of schizophrenia (SCZ) were discussed; the causes of this disease are not yet clear. Using ELISA, it was shown that titers of autoantibodies against myelin basic protein (MBP) in SCZ patients are ~1.8-fold higher than in healthy individuals but 5.0-fold lower than in patients with multiple sclerosis. Several rigid criteria were checked to show that the MBP-hydrolyzing activity is an intrinsic property of SCZ IgGs. Approximately 82% electrophoretically homogeneous SCZ IgGs purified using several affinity sorbents including Sepharose with immobilized MBP hydrolyze specifically only MBP but not many other tested proteins. The average relative activity of IgGs from patients with negative symptoms was 2.5-fold higher than that of patients with positive symptoms of SCZ, and it increases with the duration of this pathology. It was shown that abzymes are the earliest statistically significant markers of many autoimmune pathologies. Our findings surmise that the immune systems of individual SCZ patients can generate a variety of anti-MBP abzymes with different catalytic properties, which can attack MBP of the myelin-proteolipid shell of axons. Therefore, autoimmune processes together with other mechanisms can play an important role in SCZ pathogenesis. MBP-hydrolyzing antibodies were previously detected in the blood of 80% to 90% of patients with systemic lupus erythematosus (SLE) and multiple sclerosis (MS). In addition, some similar neuropsychiatric indicators of disease common to SLE, MS, and SCZ were described in the literature. Thus, the destruction of the myelin sheath and the production of MBP-hydrolyzing antibodies can be a common phenomenon for some different diseases.

A pharmacogenetic study of patients with schizophrenia from West Siberia gets insight into dopaminergic mechanisms of antipsychotic-induced hyperprolactinemia.

BACKGROUND: Hyperprolactinemia (HPRL) is a classical side effect of antipsychotic drugs primarily attributed to blockade of dopamine D2 receptors (DRD2s) on the membranes of lactotroph cells within the pituitary gland. Certain antipsychotic drugs, e.g. risperidone, are more likely to induce HPRL because of relative accumulation within the adenohypophysis. Nevertheless, due to competition for pituitary DRD2s by high dopamine levels may limit antipsychotic-induced HPRL. Moreover, the activity of prolactin-producing lactotrophs also depends on other hormones which are regulated by the extra-pituitary activity of dopamine receptors, dopamine transporters, enzymes of neurotransmitter metabolism and other factors. Polymorphic variants in the genes coding for these receptors and proteins can have functional significance and influence on the development of hyperprolactinemia. METHODS: A set of 41 SNPs of genes for dopamine receptors DRD1, DRD2, DRD3, DRD4, the dopamine transporter SLC6A3 and dopamine catabolizing enzymes MAOA and MAOB was investigated in a population of 446 Caucasians (221 males/225 females) with a clinical diagnosis of schizophrenia (according to ICD-10: F20) with and without HPRL who were treated with classical and/or atypical antipsychotic drugs. Additive genetic model was tested and the analysis was carried out in the total group and in subgroup stratified by the use of risperidone/paliperidone. RESULTS: One statistically significant association between polymorphic variant rs1799836 of MAOB gene and HPRL in men was found in the total group. Furthermore, the rs40184 and rs3863145 variants in SLC6A3 gene appeared to be associated with HPRL in the subgroup of patients using the risperidone/paliperidone, but not with HPRL induced by other antipsychotic drugs. CONCLUSIONS: Our results indicate that genetic variants of MAOB and SLC6A3 may have consequences on the modulation of prolactin secretion. A further search for genetic markers associated with the development of antipsychotic-related hyperprolactinemia in schizophrenic patients is needed.

No evidence so far of a major role of AKT1 and GSK3B in the pathogenesis of antipsychotic-induced tardive dyskinesia.

OBJECTIVE: AKT1 and GSK3B take part in one of the intracellular cascades activated by the D2 dopamine receptor (DRD2). This receptor is antagonized by antipsychotics and plays a role in the pathogenesis of antipsychotic-induced tardive dyskinesia (TD). The present study investigated association of several polymorphisms in the two candidate genes, AKT1 and GSK3B, with TD in antipsychotic-treated patients with schizophrenia. METHODS: DNA samples from 449 patients from several Siberian regions (Russia) were genotyped, and the results were analyzed using chi-squared tests and analyses of variance. RESULTS: Antipsychotic-induced TD was not associated with either of the tested functional polymorphisms (rs334558, rs1130214, and rs3730358). CONCLUSIONS: Despite regulation of AKT1 and GSK3B by DRD2, we found no evidence that these two kinases play a major role in the pathogenesis of antipsychotic-induced TD. These results agree with previously published data and necessitate further exploration of other pathogenic mechanisms, such as neurotoxicity due to excessive dopamine metabolism.

Polymorphisms of Catechol-O-Methyl Transferase (COMT) Gene in Vulnerability to Levodopa-Induced Dyskinesia.

PURPOSE: Parkinson's disease (PD), a common neurodegenerative disorder, is usually treated with Levodopa (L-DOPA). The use of this drug, however, is severely limited by the development of side effects of the motor system: Levodopa-induced dyskinesia (LID). The aim of this study is to investigate the association between seven COMT gene single-nucleotide polymorphisms (SNPs) and the development of LID in patients with PD. METHODS: 232 Caucasian patients with PD were investigated. 212 patients with PD received Levodopa therapy. Dyskinesia was assessed with the use of the Abnormal Involuntary Movement Scale (AIMS).  Genotyping was carried out on seven SNPs of the COMT gene (rs4680, rs6269, rs4633, rs4818, rs769224, rs165774, rs174696) using a real-time PCR method, and blind to the clinical status of the subjects. RESULTS: We found association between four SNPs, rs165774, rs4818, rs4633, rs4680, and LID. When the duration of disease was added as a covariate in regression analysis, however, the results did not reach statistical significance. Only the additive model for rs165774 was found to be close to be statistical significance (OR = 1.627 [0.976-2.741], permutation p = 0.057). CONCLUSIONS: The results failed to clearly support a contribution of the studied polymorphisms; this may be related to a dominant relationship with the disease duration confounding the effect on the prevalence of LID.

Association of Polymorphisms of Serotonin Transporter (5HTTLPR) and 5-HT2C Receptor Genes with Criminal Behavior in Russian Criminal Offenders.

BACKGROUND: Human aggression is a heterogeneous behavior with biological, psychological, and social backgrounds. As the biological mechanisms that regulate aggression are components of both reward-seeking and adversity-fleeing behavior, these phenomena are difficult to disentangle into separate neurochemical processes. Nevertheless, evidence exists linking some forms of aggression to aberrant serotonergic neurotransmission. We determined possible associations between 6 serotonergic neurotransmission-related gene variants and severe criminal offenses. METHODS: Male Russian prisoners who were convicted for murder (n = 117) or theft (n = 77) were genotyped for variants of the serotonin transporter (5HTTLPR), tryptophan hydroxylase, tryptophan-2,3-dioxygenase, or type 2C (5-HT2C) receptor genes and compared with general-population male controls (n = 161). Prisoners were psychologically phenotyped using the Buss-Durkee Hostility Inventory and the Beck Depression Inventory. RESULTS: No differences were found between murderers and thieves either concerning genotypes or concerning psychological measures. Comparison of polymorphism distribution between groups of prisoners and controls revealed highly significant associations of 5HTTLPR and 5-HTR2C (rs6318) gene polymorphisms with being convicted for criminal behavior. CONCLUSIONS: The lack of biological differences between the 2 groups of prisoners indicates that the studied 5HT-related genes do not differentiate between the types of crimes committed.

Association study indicates a protective role of phosphatidylinositol-4-phosphate-5-kinase against tardive dyskinesia.

BACKGROUND: Tardive dyskinesia is a disorder characterized by involuntary muscle movements that occur as a complication of long-term treatment with antipsychotic drugs. It has been suggested to be related to a malfunctioning of the indirect pathway of the motor part of the cortical-striatal-thalamic-cortical circuit, which may be caused by oxidative stress-induced neurotoxicity. METHODS: The purpose of our study was to investigate the possible association between phosphatidylinositol-4-phosphate-5-kinase type IIa (PIP5K2A) function and tardive dyskinesia in 491 Caucasian patients with schizophrenia from 3 different psychiatric institutes in West Siberia. The Abnormal Involuntary Movement Scale was used to assess tardive dyskinesia. Individuals were genotyped for 3 single nucleotide polymorphisms in PIP5K2A gene: rs10828317, rs746203, and rs8341. RESULTS: A significant association was established between the functional mutation N251S-polymorphism of the PIP5K2A gene (rs10828317) and tardive dyskinesia, while the other 2 examined nonfunctional single nucleotide polymorphisms were not related. CONCLUSIONS: We conclude from this association that PIP5K2A is possibly involved in a mechanism protecting against tardive dyskinesia-inducing neurotoxicity. This corresponds to our hypothesis that tardive dyskinesia is related to neurotoxicity at striatal indirect pathway medium-sized spiny neurons.

Untargeted Plasma Metabolomic Profiling in Patients with Depressive Disorders: A Preliminary Study.

Depressive disorder is a multifactorial disease that is based on dysfunctions in mental and biological processes. The search for biomarkers can improve its diagnosis, personalize therapy, and lead to a deep understanding of the biochemical processes underlying depression. The purpose of this work was a metabolomic analysis of blood serum to classify patients with depressive disorders and healthy individuals using Compound Discoverer software. Using high-resolution mass spectrometry, blood plasma samples from 60 people were analyzed, of which 30 were included in a comparison group (healthy donors), and 30 were patients with a depressive episode (F32.11) and recurrent depressive disorder (F33.11). Differences between patient and control groups were identified using the built-in utilities in Compound Discoverer software. Compounds were identified by their accurate mass and fragment patterns using the mzCloud database and tentatively identified by their exact mass using the ChemSpider search engine and the KEGG, ChEBI, FDA UNII-NLM, Human Metabolome and LipidMAPS databases. We identified 18 metabolites that could divide patients with depressive disorders from healthy donors. Of these, only two compounds were tentatively identified using the mzCloud database (betaine and piperine) based on their fragmentation spectra. For three compounds ((4S,5S,8S,10R)-4,5,8-trihydroxy-10-methyl-3,4,5,8,9,10-hexahydro-2H-oxecin-2-one, (2E,4E)-N-(2-hydroxy-2-methylpropyl)-2,4-tetradecadienamide and 17α-methyl-androstan-3-hydroxyimine-17ß-ol), matches were found in the mzCloud database but with low score, which could not serve as reliable evidence of their structure. Another 13 compounds were identified by their exact mass in the ChemSpider database, 9 (g-butyrobetaine, 6-diazonio-5-oxo-L-norleucine, 11-aminoundecanoic acid, methyl N-acetyl-2-diazonionorleucinate, glycyl-glycyl-argininal, dilaurylmethylamine, 12-ketodeoxycholic acid, dicetylamine, 1-linoleoyl-2-hydroxy-sn-glycero-3-PC) had only molecular formulas proposed, and 4 were unidentified. Thus, the use of Compound Discoverer software alone was not sufficient to identify all revealed metabolites. Nevertheless, the combination of the found metabolites made it possible to divide patients with depressive disorders from healthy donors.

NOS1AP Gene Variants and Their Role in Metabolic Syndrome: A Study of Patients with Schizophrenia.

Metabolic syndrome (MetS) is common among schizophrenia patients, and one of MetS's causes may be an imbalance in nitric oxide regulation. In this study, we examined associations of three polymorphic variants of the nitric oxide synthase 1 adapter protein (NOS1AP) gene with MetS in schizophrenia. NOS1AP regulates neuronal nitric oxide synthase, which controls intracellular calcium levels and may influence insulin secretion. The aim of the investigation was to study polymorphic variants of the NOS1AP gene as possible markers of MetS in patients with schizophrenia. A total of 489 Caucasian patients with schizophrenia (ICD-10) from Siberia (Russia) were included in the study, and 131 (26.8%) patients had MetS (IDF classification, 2007). The participants were genotyped for three single-nucleotide polymorphisms in NOS1AP (rs12143842, rs10494366, and rs12029454). Logistic regression was used for association analysis. Single-nucleotide polymorphisms, sex, and age served as covariates; the dependent variable was the coded parameter of the presence/absence of MetS. Polymorphisms rs12143842 and rs10494366 showed a stable association even after Bonferroni's correction for multiple comparisons (p = 0.005 and 0.002, respectively), indicating a statistically significant contribution of these polymorphic variants to the pathogenesis of MetS. Our results suggest that in patients with schizophrenia, NOS1AP may be involved in MetS pathophysiology.

EEG alpha band characteristics in patients with a depressive episode within recurrent and bipolar depression.

BACKGROUND: The search for biological markers for the differential diagnosis of recurrent depression and bipolar depression is an important undertaking in modern psychiatry. Electroencephalography (EEG) is one of the promising tools in addressing this challenge. AIM: To identify differences in the quantitative characteristics of the electroencephalographic alpha band activity in patients with a depressive episode within the framework of recurrent depression and bipolar depression. METHODS: Two groups of patients (all women) were formed: one consisting of subjects with recurrent depressive disorder and one with subjects experiencing a current mild/moderate episode (30 patients), and subjects with bipolar affective disorder or a current episode of mild or moderate depression (30 patients). The groups did not receive pharmacotherapy and did not differ in their socio-demographic parameters or total score on the Hamilton depression scale. A baseline electroencephalogram was recorded, and the quantitative characteristics of the alpha band activity were analyzed, including the absolute spectral power, interhemispheric coherence, and EEG activation. RESULTS: The patients with recurrent depressive disorder demonstrated statistically significantly lower values of the average absolute spectral power of the alpha band (z=2.481; p=0.042), as well as less alpha attenuation from eyes closed to eyes open (z=2.573; p=0.035), as compared with the patients with bipolar affective disorder. CONCLUSION: The presented quantitative characteristics of alpha activity are confirmation that patients with affective disorders of different origins also display distinctive electrophysiological features which can become promising biomarkers and could help separate bipolar depression from the recurrent type.

Building Predictive Models for Schizophrenia Diagnosis with Peripheral Inflammatory Biomarkers.

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.

Association of Single Nucleotide Polymorphisms of Cytokine Genes with Depression, Schizophrenia and Bipolar Disorder.

Immune gene variants are known to be associated with the risk of psychiatric disorders, their clinical manifestations, and their response to therapy. This narrative review summarizes the current literature over the past decade on the association of polymorphic variants of cytokine genes with risk, severity, and response to treatment for severe mental disorders such as bipolar disorder, depression, and schizophrenia. A search of literature in databases was carried out using keywords related to depressive disorder, bipolar disorder, schizophrenia, inflammation, and cytokines. Gene lists were extracted from publications to identify common genes and pathways for these mental disorders. Associations between polymorphic variants of the IL1B, IL6, and TNFA genes were the most replicated and relevant in depression. Polymorphic variants of the IL1B, IL6, IL6R, IL10, IL17A, and TNFA genes have been associated with schizophrenia. Bipolar disorder has mainly been associated with polymorphic variants of the IL1B gene. Interestingly, the IL6R gene polymorphism (rs2228145) was associated with all three diseases. Some cytokine genes have also been associated with clinical presentation and response to pharmacotherapy. There is also evidence that some specific polymorphic variants may affect the expression of cytokine genes. Thus, the data from this review indicate a link between neuroinflammation and severe mental disorders.

Cell Adhesion Molecules in Schizophrenia Patients with Metabolic Syndrome.

Metabolic syndrome (MetS) is a common comorbidity of schizophrenia and significantly shortens life expectancy of the patients. Intercellular (ICAM), vascular (VCAM), and neural (NCAM) cell adhesion molecules (CAMs) mediate neuroinflammatory processes, and their soluble forms (e.g., sICAM) in plasma are present in parallel with their cell-bound forms. In this study, their serum levels were examined in 211 white Siberian patients with paranoid schizophrenia (82 patients with and 129 without MetS according to the 2005 International Diabetes Federation criteria). Serum levels of CAMs were determined with Magpix and Luminex 200 (Luminex, Austin, TX, USA) using xMAP Technology. The level of sICAM-1 was significantly higher and that of sVCAM-1 significantly lower in patients with MetS compared to patients without MetS. Levels of NCAM did not differ between the groups. More pronounced Spearman's correlations between CAMs, age, duration of schizophrenia, and body-mass index were observed among patients without MetS than among patients with MetS. Our results are consistent with MetS's being associated with endothelial dysfunction along with other components of inflammation. Through these endothelial components of peripheral inflammatory processes, MetS might induce intracerebral neuroinflammatory changes, but further investigation is needed to confirm this.

Serum Levels of S100B Protein and Myelin Basic Protein as a Potential Biomarkers of Recurrent Depressive Disorders.

Nowadays, nervous tissue damage proteins in serum are considered promising drug targets and biomarkers of Mood Disorders. In a cross-sectional naturalistic study, the S100B, MBP and GFAP levels in the blood serum were compared between two diagnostic groups (patients with Depressive Episode (DE, n = 28) and patients with Recurrent Depressive Disorder (RDD, n = 21)), and healthy controls (n = 25). The diagnostic value of serum markers was assessed by ROC analysis. In the DE group, we did not find changed levels of S100B, MBP and GFAP compared with controls. In the RDD group, we found decreased S100B level (p = 0.011) and increased MBP level (p = 0.015) in comparison to those in healthy controls. Provided ROC analysis indicates that MBP contributes to the development of a DE (AUC = 0.676; 95%Cl 0.525-0.826; p = 0.028), and S100B and MBP have a significant effect on the development of RDD (AUC = 0.732; 95%Cl 0.560-0.903; p = 0.013 and AUC = 0.712; 95%Cl 0.557-0.867; p = 0.015, correspondingly). The study of serum markers of nervous tissue damage in patients with a current DE indicates signs of disintegration of structural and functional relationships, dysfunction of gliotransmission, and impaired secretion of neurospecific proteins. Modified functions of astrocytes and oligodendrocytes are implicated in the pathophysiology of RDD.