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BACKGROUND: Recently a significant part of schizophrenia studies have been focused on the role of cytokines, especially interleukin-6 (IL-6). Some authors have suggested a pathogenetic role for IL-6 in schizophrenia and concluded that therapy that centers on suppressing IL-6 activity may prove beneficial for certain categories of patients with the disorder. However, many questions about whether the changes in IL-6 levels in schizophrenia are primary, related to symptoms or caused by therapy, are concomitant metabolic disorders, are related to smoking or other secondary factors remain unanswered. AIM: To assess the level of serum IL-6 in patients with schizophrenia in comparison with healthy controls, as well as to study its association with clinical and socio-demographic characteristics. METHODS: Some 125 patients with schizophrenia and 95 healthy volunteers were examined. The evaluation of IL-6 was performed by enzyme immunoassay. All patients were assessed using standardized psychometric instruments. Information from patient medical records on the course of the disease and treatment was analyzed. RESULTS: The level of IL-6 was significantly higher in the patients than in the healthy volunteers (z=2.58; p=0.0099), but among men the difference between the patients and volunteers was not significant. Statistically significant correlations were found between the level of serum IL-6 and the severity of the cognitive impairment of patients: (auditory [ρ=-0.31; p=0.00063] and working memory [ρ=-0.25; p=0.0065], hand-eye coordination [ρ=-0.29; p=0.0011], verbal fluency [ρ=-0.28; p=0.0019] and problem-solving capacity [ρ=-0.22; p=0.013]), total severity of schizophrenia symptoms (PANSS, ρ=0.22; p=0.016), PANSS positive subscale (ρ=0.18; p=0.048), and the age of manifestation (ρ=0.20; p=0.025) and disease duration (ρ=0.18; p=0.043). The level of IL-6 was the lowest in patients treated with third-generation antipsychotics, and the highest in those treated with first-generation antipsychotics (H=6.36; p=0.042). Moreover, in hospital patients, the level of IL-6 was significantly higher than in outpatients and inpatients hospitals (H=18.59; p=0.0001). CONCLUSION: The study confirmed that there are associations between the serum IL-6 level and schizophrenia, the age of the patient, duration of the disease and how late in one's life cycle it began manifesting itself, as well as a number of clinical characteristics. Considering that IL-6 is associated with a wide range of symptoms that are loosely controlled by antipsychotics, this biochemical marker needs to be studied to look into how closely its level tracks with an unfavorable course of schizophrenia. That would require further prospective studies.
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At least 50% of factors predisposing to alcohol dependence (AD) are genetic and women affected with this disorder present with more psychiatric comorbidities, probably indicating different genetic factors involved. We aimed to run a genome-wide association study (GWAS) followed by a bioinformatic functional annotation of associated genomic regions in patients with AD and eight related clinical measures. A genome-wide significant association of rs220677 with AD (p-value = 1.33 × 10-8 calculated with the Yates-corrected χ2 test under the assumption of dominant inheritance) was discovered in female patients. Associations of AD and related clinical measures with seven other single nucleotide polymorphisms listed in previous GWASs of psychiatric and addiction traits were differently replicated in male and female patients. The bioinformatic analysis showed that regulatory elements in the eight associated linkage disequilibrium blocks define the expression of 80 protein-coding genes. Nearly 68% of these and of 120 previously published coding genes associated with alcohol phenotypes directly interact in a single network, where BDNF is the most significant hub gene. This study indicates that several genes behind the pathogenesis of AD are different in male and female patients, but implicated molecular mechanisms are functionally connected. The study also reveals a central role of BDNF in the pathogenesis of AD.
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We provide an overview of the recent achievements in psychiatric genetics research in the Russian Federation and present genotype-phenotype, population, epigenetic, cytogenetic, functional, ENIGMA, and pharmacogenetic studies, with an emphasis on genome-wide association studies. The genetic backgrounds of mental illnesses in the polyethnic and multicultural population of the Russian Federation are still understudied. Furthermore, genetic, genomic, and pharmacogenetic data from the Russian Federation are not adequately represented in the international scientific literature, are currently not available for meta-analyses and have never been compared with data from other populations. Most of these problems cannot be solved by individual centers working in isolation but warrant a truly collaborative effort that brings together all the major psychiatric genetic research centers in the Russian Federation in a national consortium. For this reason, we have established the Russian National Consortium for Psychiatric Genetics (RNCPG) with the aim to strengthen the power and rigor of psychiatric genetics research in the Russian Federation and enhance the international compatibility of this research.The consortium is set up as an open organization that will facilitate collaborations on complex biomedical research projects in human mental health in the Russian Federation and abroad. These projects will include genotyping, sequencing, transcriptome and epigenome analysis, metabolomics, and a wide array of other state-of-the-art analyses. Here, we discuss the challenges we face and the approaches we will take to unlock the huge potential that the Russian Federation holds for the worldwide psychiatric genetics community.
