Genome-wide association studies (GWASs) discovered multiple genetic variants associated with
schizophrenia. Te next step (post-GWAS analysis) is aimed at identifying the causal genetic variants and
biological mechanisms underlying the associations with disease risk. Te following strategies are considered:
the study of transcriptional regulation in neuronal human cells and the use of epigenomic information for
searching for regulatory elements involved in the pathogenesis of schizophrenia. Te frst strategy includes
identifcation of neuronal enhancers, mapping of potential target genes and functional confrmation of
enhancer-promoter interactions. Te second approach is focused on the identifcation of transcriptional factors, which appear to be master regulators of expression.

Is this paper we present a summary of our association analyses of schizophrenia polygenic risk score with a number of phenotypes in a large cohort of people from the UK population (N=442,192). We show that individuals with higher genetic loading to schizophrenia who have not been diagnosed with neurodevelopmental disorders are likely to have some cognitive deficits. Although these deficits may be subtle, they can result in significant effects on educational attainment and professional occupation. We also show that the relationship between schizophrenia liability and fecundity is consistent with sexual selection, with liability in unaffected people being associated with a net increase in fecundity, thereby supporting the persistence of schizophrenia risk alleles.

An overview of a number of research papers examines application of pharmacogenetic tests in narcology. It has been proven that a system of pharmacogenetic tests can be used for the development of a polygenic predictive system which can provide a preliminary forecast of effectiveness and tolerability of a treatment as part of the individualization of addiction pharmacotherapy. Moreover, methods of genetic engineering can be a new emerging approach in the treatment of addiction.

The pathogenesis of the development of drug-induced disorders while taking antipsychotic drugs is not well understood. The aim of the work is to study polymorphic variants of the multidrug resistance protein gene and genes encoding the metabolism and synthesis of dopamine and serotonin enzymes in antipsychotic-induced hyperprolactinemia in schizophrenia patients. As a result of a comprehensive study of 446 patients with schizophrenia and genotyping of 25 polymorphic variants of the MDR1, COMT, MAO-A, MAO-B, TPH1 and TPH2 genes, associations of polymorphisms rs1045642, rs2032582, rs4148739 (MDR1), rs6323 (MAO-А), rs1799836 (MAO-B) were revealed with the development of hyperprolactinemia. Further research is needed to develop personalized approaches to therapy.

«Omic» biomarkers are promising tools for personalizing pharmacotherapy, including and mental illness because allow predicting an individual profile of the effectiveness and safety of psychotropic drugs. «Omics» biomarkers include pharmacogenomic, pharmacoproteomic, pharmacotranscriptome, pharmacometabolic biomarkers. A methodology for the development of «omcs» biomarkers of personalization of pharmacotherapy is presented: from assessing the problems of pharmacotherapy to the system of implanting biomarkers into real clinical practice.

Lithium remains a first-line pharmacological treatment of bipolar disorder (BD). However, treatment response is heterogeneous, with several lines of evidence implicating genetic factors. Unfortunately, neither hypothesis-driven approaches nor initial genome-wide association studies (GWAS) were successful in identifying genetic drivers of response heterogeneity, probably due to low statistical power and different phenotype measurements. Recently, a GWAS of the Consortium of Lithium Genetics (ConLiGen) has identified four single nucleotide polymorphisms (SNPs) mediating response to lithium, located in genes for two long non-coding RNAs. This success was only possible by international collaboration and the use of an established lithium response scale. The findings await further replication.

Major psychiatric disorders including alcohol use disorder are considered multigenic and the smallness of effects of individual genes may be attributed to either complex biological mechanisms or geneenvironment interactions. The latter explanation is highlighted by the relatively fast changes in secular trends and in cohort effects on alcohol use disorder. Interactions of candidate gene variants with birth cohort have been found in the Estonian Children Personality Behaviour and Health Study, a longitudinal investigation from 1998 with a sample highly representative of birth cohorts within a region. Such interactions regarding initiation of alcohol use or alcohol use disorder have been revealed for e.g., 5-HTTLPR, VMAT1, OXR and NRG1, and suggest that rapid alterations in the socioeconomic environment promote changes in the genetic vulnerability to environmental risks factors such as alcohol.

The background, history of creation, goals and objectives, as well as the principles of organization and work of the Russian National Consortium for Psychiatric Genetics (RNCPG) are described. The first results of the work for two years have been summarized, a brief overview of completed, ongoing and planned projects under the RNCPG is given.

It is established that Substance use disorders (SUDs) and Parkinson’s Disease (PD) among many other neuropsychiatric disorders are dopamine (DA)-related brain disorders with strong heritability. However, it is unclear whether DA-associated genetic risks share commonality across these disorders. This study utilizes the Genotype and Phenotype Database (dbGaP), by downloading related genome-wide association studies (GWAS) for individual genotype/phenotypes. According to our results DA pathways are significantly implicated in the genetic etiology of both SUDs and PD but much more in the former. Epistatic effects may represent a major portion of missing heritability observed in current main effect-oriented GWAS analyses.

Despite many years of work on dopaminergic mechanisms of alcohol addiction, much of this evidence remains mostly correlative in nature. Fortunately, the latest technological advances have provided the opportunity to explore the causal role of neurochemical changes within brain regions involved in addictive behaviors. In this work using optogenetics, we have attempted to answer the question of how dopamine release dynamics control the motivational component of alcohol drinking behavior.

The genomic research is one of the most dynamically developing fields both in the worldwide and in Russia. Currently, the genetic approaches in psychiatry are used to solve the practical and scientific problems related to medical genetic counseling, identification of the genetic factors associated with characteristics of metabolism of medicines or development of their side effects, as well as to develop the new approaches to classification of psychiatric disorders. Given the complexity and the unresolved nature of the several methodological issues related to ethics and protection of the rights of patients with mental disorders, the legal regulation of genomic research in this category of patients is a specific interdisciplinary challenge which solution requires combining of the competencies of lawyers, medical ethics specialists, psychiatrists, psychologists, geneticists.

Current trends in the concept of therapeutically resistant depression (TRD) tend to narrow its very heterogeneous group of patients. One of the most rapidly developing areas in the biological paradigm of TRD is genetic research aimed at finding biomarkers for predicting the therapeutic response. Obviously, the genetic risks of TR are not limited to combinations of genome genetic variants, but it also has phenotypic manifestations at all levels of phenotype formation. According to the fundamental possibility of achieving remission states, therapeutic resistance can be divided into relative and absolute. At present, it can be said that patients with relative and absolute resistance represent two biologically heterogeneous groups, the isolation of which requires the development of special laboratory approaches that will contribute to the development of a personalized approach to therapy.

Affective disorders — including anxiety and depression — are the most prevalent human brain diseases. Stress is the most common cause of these human psychopathologies, and is also often used to develop their experimental models in animals. In addition to genetic and environmental factors, genomic and epigenetic processes play an important role in affective pathogenesis. The aim of the present study is to examine the expression of brain genes in mice in the chronic 20-day social stress model developed by Prof. N.N. Kudryavtseva (Institute of Cytology and Genetics) and to experimentally test the hypothesis on ‘genes-integrators’ whose brain activity can specifically integrate anxiety-depressive mechanisms. The report will for the first time provide data on the existence of several such putative brain genes whose expression in the hippocampus and cortex changes dynamically as stress transitions from the «anxiety» (10 days) to the «depressive» phase (20 days), including a number of cytokine and cellular structural genes whose expression is specifically altered only in the «transitional» stage (15 days). The findings provide a new perspective on the complex genomics of the anxiety-depressive pathogenesis of the CNS, and can be translationally significant, including in terms of finding new potential targets for the therapy of anxiety and depression based on such ‘gene-integrators’.

Lithium is an indispensable tool of modern psychiatry. Although it is well-known that response to lithium is a familial trait, available research on pharmacogenetics regarding lithium treatment has, in the past, produced few reproducible results. The Consortium of Lithium Genetics (ConLiGen) was initiated by Thomas G. Schulze and Francis J. McMahon in 2008 to overcome these limitations. To date, researchers from 39 countries have joined the consortium, making it a truly international effort. A hallmark of the consortium is the use of an 11-point lithium response rating scale defined by Martin Alda and colleagues. The pooling of genotype data from over 2,500 patients phenotyped with this standardized response scale, have led to initial successes, which form the basis for further research.

Both genetic and environmental factors play a major role in the etiology of mental illnesses. Longitudinal studies collecting many phenotypes and biomaterials help to elucidate this complex interplay. PsyCourse is an observational longitudinal multi-center (19 centers) study of severe mental disorders conducted in Germany and Austria, that, to date, collected data from more than 1,500 patients and control individuals. Here, we give an overview of the key properties and, specifically, the infrastructure of the PsyCourse study. Beside the study protocol, we provide information on IT tools, data management, data protection, quality control, data analysis, and data sharing with collaborators. We also highlight the need for fundamental preparation.

Personalizing patient care through the use of individual genome-wide information is one of the key challenges for psychiatry in the post-genomic era. Prognostic multivariate models incorporating polygenic risk scores (PGRS) seem to be a promising tool. The article discusses the potential of fully polygenic models, in which all predictors are represented as PGRS of the corresponding phenotypes, and models, in which the individual genetic information embedded in the PGRS is supplemented with epigenetic data.

Studies of suicide genetics can be divided into 3 periods: 1) period of classical methods of behavioral genetics; 2) candidate genes association studies, and 3) genome-wide association studies. The majority of studies using candidate genes strategy has been dedicated to main neurotransmitter systems (serotonine, catecholamines, GABA, excitatory aminoacids system, etc.) and in the last decade — to genes of the stress-reactivity system and neurotrophins. On the other hand among main GWAS findings are genes that are involved in neurodevelopment, neuroplasticity, cell adhesion and migration, proliferation and intracellular signaling, as well as immune system functions. We consider it a confirmation of the relevance of the stressvulnerability models that imply key role of the early development and involvement of the neuroplasticity, as well as models that focus on stress as a systemic reaction of the organism in pathogenesis of suicidal behavior. It should be noted that findings of different GWAS studies most often do not coincide and in general produce rather heterogeneous picture. It may be due to differing bioinformatics approaches, phenotypes description differences and study design peculiarities. We consider that more research is needed in all three directions with involvement of NGS approaches, in particular whole-exome sequencing.

Purpose: The present study was aimed to evaluate the effect of the opioid receptors genes and dopamine system genes polymorphisms on the treatment outcomes of opioid dependence with implantable and oral naltrexone in randomized double blinded double dummy placebo controlled clinical trial. Methods: 306 patients with opioid dependence were randomized in 3 treatment groups (102 ss in each). The first group received implantation of 1000 mg naltrexone every 2 months during the 6 months period + oral naltrexone placebo; the second group — placebo implant every 2 months + oral naltrexone (50mg/day), and the third group — placebo implant + oral naltrexone placebo. All enrolled participants provided blood sample at baseline for genetic analysis of polymorphisms in following genes: mu-opioid receptor (OPRM1), kappa-opioid receptor (OPRK1), catechol-O-methyltransferase (COMT), dopamine receptors types 2 (DRD2) and 4 (DRD4), dopamine-beta-hydroxylase, and dopamine transporter (DAT1). Results: Regardless of provided treatment several polymorphisms of tested genes were associated with high risk of relapse: allele L (2R) DRD4 120bp (p=0.05; OR(95% CI)=3.3(1.1-10.1) ); allele С DRD2 NcoI (р=0,051 OR(95% CI) = 2,86 (1,09 — 7,52); genotype 9.9 DAT VNTR40bp (р=0,04; RR(95% CI) = 1,4(1,3 — 1,5)); on the contrary variants of polymorphisms (СС+СТ)-(ТТ)) of genes (OPRK1- DRD2Ncol) increased the chance to complete the treatment program (р=0,004; OR(95% CI) = 7.4 (1.8 — 30.4)), Kaplan-Meier survival analysis, р=0,016). The probability of completing treatment program by carriers of all these above mentioned variants of polymorphisms (OPRK1DRD2Ncol) was higher for oral naltrexone group (p=0.016), lower for double placebo group (p=0.015), but did not influence treatment outcomes in naltrexone-implant group. Conclusion: Naltrexone-implant is an effective medication for treatment of opioid dependence and its effectiveness exceeds oral naltrexone and placebo. The study showed joint influence of opioid receptor genes and genes of dopaminergic system on the treatment outcomes of opioid dependence. Genetic analysis is useful for determining potential responders to naltrexone treatment of opioid dependence.

The Research Domain Criteria (RDoC) project, the neurobiological research flagship in psychiatry, was originally introduced as an alternative to the traditional DSM and ICD classifications. However, RDoC and ICD / DSM can become complementary, rather than mutually exclusive. The clinical psychopathological method remains valuable because it’s the only source of directly observable data. Computational science is a promising tool for combining psychopathological and neurobiological data in future.

The paper presents the results of the literature review and the authors’ own studies of the association of several several single-nucleotide genetic polymorphisms (SNP), which affect one-carbon metabolism, with a risk of schizophrenia and the severity of some clusters of its symptoms. Directions for further study of the role of a number of SNP of enzymes in the folate metabolism cycle and related biochemical processes in schizophrenia (in particular, their influence on the effect of personalized correction of one-carbon metabolism disorders) are determined.

The study of effects of genetic polymorphisms implicated in dopamine (COMT, DRD2) and GABA (GAD1) activities in the prefrontal cortex on antisaccades (AS) and evoked potential P300 measures was conducted with participation of 55 healthy subjects and 72 schizophrenic patients. The significant interaction of genotype and disease was found for most of the studied AS and P300 measures. The worse task performance and decreased efficacy of cortical activation were revealed for the associated with schizophrenia risk polymorphisms.

In several unrelated small samples examined correlation between genetic risk of chemical dependence, calculated on the basis of the contribution of geomarkers dopamine system, and phenotype of adolescents 14-17 years of age, not suffering from addiction. When genetic risk increases, the tendency to behavioural disorders increases, the tendency to abandon positive forms of self-assertion increases, the intensity of euphoria increases at the first drug samples, and the ability to predict the consequences of drug use decreases. The obtained correlations may be important for understanding the mechanism of dependence formation in adolescents with high genetic risk and development of individual prevention programs. However, these observations need to be confirmed in more representative studies.

Currently, there is a lack of pharmacogenetic research of antipsychotics’ safety in children and adolescents with acute psychotic episodes. Genetic polymorphisms of CYP2D6 and ABCB1 are the most likely candidates for such studies. AIM.To establish possible associations of CYP3A, CYP2D6, ABCB1 polymorphisms with safety of antipsychotics of an acute psychotic episode in adolescents during the first 14 days of treatment. MATERIALS AND METHODS. We observed 53 adolescents, hospitalized with acute psychotic episode, during 14 days of treatment. Mean age was 15,08±1,7 years. All patients took antipsychotic as the main drug. The tolerance to antipsychotics was assessed using UKU SERS, SAS, BARS. We collected a buccal epitelium from each patient and genotyped CYP3A4*22 (rs2740574), CYP3A5*3 (6986A>G, rs7767746), CYP2D6*4, *10 (rs3892097, rs1065852), ABCB1 1236C>T (rs1128503), 2677G>T/A (rs2032582), 3435C>T (rs1045642) by real-time PCR. RESULTS. Scores of UKU SERS, SAS, BARS, AIMS scales did not correlated with average doses of antipsychotics. Distribution of genetic polymorphisms were in the Hardy-Weinberg equilibrium. The carriage of CYP2D6*4 was associated with the presence of «Asthenia / Lassitude / lncreased Fatigability» (70% vs. 3.6%, p=0.039), the carriage of CYP2D6*10 was associated with «Increased dream activity» (53.8% vs. 22.5%, p=0.043). The «Increased Duration of Sleep» was more often observed in homozygotes according to the polymorphisms ABCB1 2677G>T/A (50% vs. 15.8%, p=0.006) and 3435C>T (41.7% vs. 8.2%, p=0.007). Carriers of TT polymorphism homozygote ABCB1 2677G>T/A also more frequently noted «Polyuria/polydypsia» (37.5% vs. 5.18%, p=0.045). CONCLUSION.Genetic polymorphisms CYP2D6*4, *10, ABCB1 2677G>T/A and 3435C>T increased a risk of adverse drug effects of antipsychotics in adolescents with acute psychotic episode.

Complicated cascade of shared biological components with a genetic basis and, probably, common triggers of the genetically posed risk are involved in the comorbidity of depressive symptoms and somatic disorders. This suggests that, under certain conditions, it can manifest both a single disease and a cluster of disorders with different phenomenological characteristics, united by common genetically mediated pathophysiological mechanisms. Based on the analysis of epidemiological, clinical, pathophysiological and genetic studies, we substantiated the hypothesis of cluster genetic comorbidity of depression and somatic diseases.

Genetic factors of mental illness are generally recognized. Here, it is shown that molecular karyotyping in combination with original bioinformatics methods offers the opportunity for effective uncovering genomic pathology, which may provide correct data on genetic factors for mental disorders in children.

The present study included the construction of polygenic risk score (PRS) models of individual differences in anxiety level, which increased values represent the endophenotype of depression and suicidal behavior, to predict these psychopathologies based on genotyping of 63 SNPs of serotoninergic, hypothalamicpituitary-adrenal and neurotrophic factors systems together with the relative leukocyte telomere length. According to logistic regression analysis, PRS models of individual differences in Neuroticism (EPI) level (P<0,2) predicted decreased risk of unipolar depression (P0.2=0,033, β=-5,24, r2=0,78) in women, which points to the necessity to consider sex during polygenic risk score analysis.

Rat line lacking the dopamine transporter (DAT-KO rats) was recently developed. Lack of DAT in these mutants manifests behaviorally as spontaneous hyperactivity and cognitive deficits. It has been shown that d-amphetamine and methylphenidate paradoxically calm down these animals. Also, the inhibition of dopamine synthesis in DAT-KO rats represents a straightforward approach for developing the model of severe dopamine deficiency exhibiting characteristic akinetic phenotype which can be reversed by treatment with L-DOPA that used in Parkinson’s disease. These results support the usefulness of DAT-KO rats as models of the disorders associated with dopaminergic dysfunction.

Non-motor symptoms are common in Parkinson`s disease and reflect the multisystem nature of the disorder. Parkinson’s disease is highly heterogeneous in early clinical features and later outcomes. This makes classifying genetic subgroups of PD relevant to clinical research and practice, particularly if they are prognostically relevant. Non-motor sypmptoms may be detrimental to patients’ functional status and sense of well-being.

Currently, the syndrome of pain dysfunction of the temporomandibular joint is not considered exclusively a local disorder, but rather is considered as a clinical outcome of the combined effect of many factors (local and systemic), which act simultaneously and determine, ultimately, the manifestation of the disease. In the framework of the biopsychosocial concept, a hypothesis has been formulated about the importance of the polymorphism of the COMT and ADRB-2 genes for the development of SDJ TMJs, which make these individuals “vulnerable” to the development of chronic pain syndromes. It was found that a decrease in COMT activity leads to an increase in the level of catecholamimes, in particular, such as adrenaline, which contribute to the formation of persistent pain states by stimulating β2-adrenergic receptors in the peripheral and central nervous system.

The gene CYP2D6 is of great interest also due to its highly polymorphic nature and involvement in a high number of medication metabolisms. The presence of polymorphisms in the CYP2D6 gene may modulate enzyme level and activity, thereby affecting individual responses to pharmacological treatment.  The purpose of this study was to investigate of CYP2D6*10 polymorphism prevalence in patients with epilepsy in the North-West and the Siberian region of the Russia. The results of the study showed differences in the prevalence of alleles responsible for “intermediate” metabolites in the North-West and Siberian regions of Russia were identified, it’s may be associated with genetic drift and accumulation of alleles typical for European and Asian populations.

Genotyping of 28 polymorphisms of 5 dopamine receptor genes and 12 polymorphisms of dopamine transporter gene was performed in 475 schizophrenia patients and 135 healthy individuals. Associations of several polymorphisms of the DRD2, DRD3 and SLC6A3 genes were identified with leading symptoms and late debut of schizophrenia.

The article presents the results of studies of associations of polymorphic variants of serotonin receptor genes and serotonin synthesis and metabolism enzymes genes with depressive disorders and the presence of clinical remission. The associations of polymorphic variants rs130058 of HTR1B gene and rs1176744 of HTR3B gene with depressive disorders was shown. Clinical remission assessed according to the CGI-S scale on the 28th day of therapy, associated with the polymorphic variant rs6298 of HTR1B gene, with remission in women, evaluated according to the HDRS-17 scale, associated polymorphic variants rs3813929 and rs1737429 of HTR2C gene. The data obtained confirm the participation of the serotonergic system in the pathogenesis of depressive disorders.

The role of protein kinases in schizophrenia is being actively studied. However, the effect of protein kinase gene polymorphisms on the clinical manifestations of the disease has been little studied. We examined 384 patients diagnosed with schizophrenia in accordance with ICD-10 (F20) (269 patients with a continuous course of schizophrenia; 115 patients with an episodic course of the disease). Genotyping of polymorphisms PIP5K2A (rs10828317, rs8341, rs746203), GSK3B (rs334558), AKT1 (rs3730358, rs1130214) was carried out by real-time PCR method. An association of rs8341 PIP5K2A with the type of course of schizophrenia was revealed. The CT genotype was associated with a continuous type of schizophrenia, the TT genotype with an episodic one. Disorders of the phosphoinositide pathway may be a possible cause of the transition to a more severe continuous course of schizophrenia.

Despite the large number of candidate genes for mental disorders, molecular mechanisms of the majority remain unknown. To fill this gap, we have studied genomic networks-candidates (instead of genes) in a group of children with brain disorders. The identification of such processes seems to be more promising for developing therapeutic strategies in contrast to candidate gene identification.

Hereditary factors contribute significantly to the development of schizophrenia. However, despite many years of research, the genetic architecture and mechanisms of the participation of genetic factors in the development of schizophrenia are not well understood. Genome-wide analyzes of genetic associations in various non-coding regions of the genome, including gene enhancers, revealed many loci associated with an increased risk of schizophrenia. In the course of the analysis of the spatial structure of the genome, we revealed the interaction of these enhancers with the promoter regions of genes involved in the metabolism of neurons. To study in more detail the functions of these genes and the participation of enhancers in their regulation, we obtained plasmid and lentiviral constructs of a functionally active transcription repressor based on the CRISPR / SpyCas9 system, as well as the endonuclease system. The use of these constructs in studies of the functions of enhancers and genes associated with the metabolism and regulation of gene expression in neurons is discussed.

Affective disorders (recurrent depressive disorder and bipolar affective disorder) are multifactorial and polygenic diseases, which suggests the involvement of multiple neurobiological mechanisms. The phenotype of affective disorders is a heterogeneous group of clinically similar psychopathological symptoms, which also makes it difficult to detect potential biomarkers and new therapeutic targets. To study families at high risk of developing affective disorders using both clinical and molecular genetic approaches can help to study the neurobiological basis of depressive conditions, as well as to identify endophenotypes of affective disorders. The most important criterion for an endophenotype is its heritability, which can be proved only within the framework of the family design of the study. Comprehensive clinical and molecular genetic studies based on family design have the best prospects.

The study was conducted with the participation of 47 healthy subjects and 48 schizophrenia patients. The different effects of Val158Met polymorphism have been found in the control and patients groups. The increased N100 amplitude and minimal number of the error responses in oddball task were revealed in healthy subjects with Val/Val genotype. In patients group Val/Val genotype was related to the decreased N100 amplitude and worse performance of oddball task.

Aim. Test the hypothesis about the effect of polymorphisms of the DA system on the risk of developing depression in patients with alcohol dependence. Material and methods. 104 patients: 64 patients with a combination of diagnoses of “alcohol dependence” and “depression” (F10.2 and F32, F33 according to ICD-10, average age 41.23 ± 9.903 years) and 40 patients with a diagnosis of alcohol dependence (F10 .2 according to ICD-10, average age 45.57 ± 10.853 years) and 113 control (average age 43.65 ± 4.318 years). Results. In patients with a combination of AD and depression, the frequency of occurrence of the C allele C polymorphism rs1611115 of the DBH gene is higher than in the control group (p = 0.087, trend). In patients with a combination of AD and depression, the frequency of occurrence of the A allele of the rs1108580 polymorphism of the DBH gene is higher than in patients with AD (p = 0.059, trend). In patients with AD allele A, the DBH gene rs1108580 polymorphism increases the risk of depression by 174.0% (p = 0.009), the DBH gene rs1108580 AA polymorphism increases the risk of depression by 684.1% (p = 0.010), the rs1108580 gene AG polymorphism rs1108580 in the gene DBH increases the risk of depression by 261.1% (p = 0.010). Conclusion. It has been shown for the first time that polymorphic variants of the rs1108580 locus of the DBH gene act as important risk factors for depression in patients with AD. Polymorphism rs1611115 of the DBH gene can also play an important role in the development of depression in patients with AD, which requires further study.

The use of atypical antipsychotic drugs has made metabolic disorders one of the most common side effect of pharmacotherapy for schizophrenic patients. The aim of this study was to assess the contribution of polymorphic variants of genes of the P450 cytochrome system to changes in body mass index in patients with schizophrenia. As a result of the study, we did not identify significant associations of genotypes and alleles of the studied polymorphic variants of the CYP2D6, CYP1A2, CYP2C19 genes with weight gain in patients with schizophrenia of Russian nationality of the Siberian region receiving antipsychotic therapy and can revealed neither protective nor predisposing effects. Metabolic syndrome and, increase in body weight especially, are complex side effect, and further studies is needed to increase successful exploration and identification of the genetic component and assess contribution.

There is a problem of insufficient effectiveness of pharmacotherapy for the relapse prevention in patients with opioid dependence. In Russian Federation naltrexone is a mainly used medication for treatment of opioid addiction. However, it has no effects on stress, craving, and impulsiveness. Alpha-2 adrenoreceptor agonists can reduce the severity of these symptoms and thus might improve effectiveness of naltrexone treatment. Pharmacogenetic analysis is useful for determining potential responders and nonresponders to the treatment of opioid dependence. The aim of this study was to evaluate the variability of response to pharmacotherapy of naltrexone and guanfacin in patients with opioid dependence syndrome. This was a multicenter, randomized, double-blind, placebo-controlled clinical trial using a pharmacogenetic approach. The good tolerability and safety of naltrexone and guanfacine combination with long-term course treatment for stabilization of remission of opioid dependence was scientifically substantiated. Was showed a moderate stress-protective and anti-craving effect of guanfacin in the period of early remission with opioid dependence syndrome. Genetic analysis is useful for determining potential responders to the treatment of opioid dependence, genotyping can increase effectiveness of pharmacotherapy.

Studied the duration of abstinence from alcohol depending on the level of genetic risk of substance abuse, calculated on the basis of the contribution of genomarkers dopamine system, the 35 adult males who abuse alcohol. It was established that the genetic risk is not associated with the duration of abstinence from alcohol in the conditions of sobriety control.

One of the common pathogenetic mechanisms of the formation of alcohol dependence and depressive disorders can be a violation of the neurotransmitter systems, in particular — dopamine. Phosphatidylinositol-4-phosphate-5-kinase type 2 alpha (PIP5K2A) plays an important role in the regulation of neuronal excitability and synaptic dopamine neurotransmission. The aim of this study was to assess the presence of associations of the PIP5K2A gene polymorphic variants with the comorbid course of alcohol dependence and depressive disorders. This study showed differences in the frequency of the genotype distribution of 3 PIP5K2A gene polymorphisms (rs946961, rs1132816, and rs1417374) both between patient groups compared with the control group, and between the patient group and the group with the comorbid course of disorders.

This review briefly describes modern approaches of data analysis in psychiatry using machine learning and gives possible prospects and common obstacles of this approach.

According to modern data, about a third of patients suffering from schizophrenia are considered treatment resistant. The metabolism of about 20% of medicines and mainly psychotropic drugs is caused by the isoenzyme CYP2D6. This article presents the data of the CYP2D6 gene study as biomarkers for the treatment resistant schizophrenia. The study included 130 patients, men (65.4%) and women (34.6%) aged 18 to 60 years with schizophrenia. Based on the results, we found no effect of rs1065852 and rs3892097 polymorphisms gene CYP2D6 on treatment resistant schizophrenia.