[Effects of oxytocin pathway gene polymorphisms and adverse childhood experiences on emotion recognition in schizophrenia spectrum disorders]. / Effekty polimorfizma genov oksitotsinergicheskogo puti i neblagopriyatnogo detskogo opyta na raspoznavanie emotsii pri rasstroistvakh shizofrenicheskogo spektra.

OBJECTIVE: To study a role of the interaction of oxytocin pathway gene polymorphisms and adverse childhood experiences (ACE) in facial emotion recognition (FER) deficits in schizophrenia. MATERIAL AND METHODS: Patients with schizophrenia spectrum disorders (n=699) completed cognitive testing, which included a FER task. We determined patients' genotypes for common polymorphisms in three of the oxytocin pathway genes which were previously associated with face perception: OXTR (rs53576, rs7632287), CD38 (rs3796863) and ARNT2 (rs4778599). The presence of ACE in the patient's history was assessed via an analysis of medical records. RESULTS: In our sample, 49% of participants experienced ACE. ANCOVA adjusted for age and gender revealed a significant interaction effect of OXTR rs53576 with ACE on FER scores (F=11.51; p<0.001; η2p=0.02). The effect remained significant when accounting for cognitive functioning and negative symptoms. Carriers of the A allele without ACE recognized emotions worse than GG homozygotes without ACE (p=0.039) and carriers of the A allele with ACE (p=0.009). CONCLUSION: The results are consistent with the notion of the A (rs53576) allele's role in sensitivity to childhood experiences that influence the psychosocial development and can be used in further studies of the oxytocin treatment of social cognition and social adaptation of patients with schizophrenia.

[Immune mechanisms of complicity of somatic pathology in the pathogenesis of mental disorders]. / Immunnye mekhanizmy souchastiya somaticheskoi patologii v patogeneze psikhicheskikh rasstroistv.

Understanding the mechanisms of the relationship between the nervous and immune systems within the framework of the concept of the key role of inflammation, taking into account the involved genetic factors in the development of a wide range of combined forms of somatic and mental diseases, is of interest for research as well as for the development of new approaches to early diagnosis and more effective treatment of these diseases. This review analyzes the immune mechanisms of the development of mental disorders in patients with somatic diseases, in particular, the transmission of an inflammatory signal from the periphery to the CNS and the implementation of the influence of inflammatory factors on neurochemical systems that determine the characteristics of mental functioning. Particular attention is paid to the processes underlying the disruption of the blood-brain barrier caused by peripheral inflammation. Modulation of neurotransmission, changes in neuroplasticity, changes in regional activity of the brain in areas associated with the functions of threat recognition, cognitive processes and memory function, the effect of cytokines on the hypothalamic-pituitary-adrenal system are considered as mechanisms of action of inflammatory factors in the brain. The need to take into account variations in the genes of pro-inflammatory cytokines, which may be the cause of increased genetic vulnerability associated with the risk mental disorders in patients suffering from a certain somatic disease, is emphasized.

[Genome-wide studies of comorbidity of somatic and mental diseases]. / Polnogenomnye issledovaniya komorbidnosti somaticheskikh i psikhicheskikh zabolevanii.

Studies of the genomic architecture of complex phenotypes, which include common somatic and mental diseases, have shown that they are characterized by a high degree of polygenicity, i.e. participation of a large number of genes associated with the risk of developing these diseases. In this regard, it is of interest to establish the genetic overlapping between these two groups of diseases. The aim of the review is to analyze genetic studies of the comorbidity of somatic and mental diseases in terms of the universality and specificity of mental disorders in somatic diseases, the reciprocal relationships of these types of pathologies, and the modulating influence of environmental factors on comorbidity. The results of the analysis indicate the existence of a common genetic predisposition to mental and somatic diseases. At the same time, the presence of common genes does not exclude the specificity of the development of mental disorders depending on a specific somatic pathology. It can be assumed that there are genes that are both unique to a particular somatic and comorbid mental illness, and genes that are common to these diseases. Common genes may have varying degrees of specificity, that is, they may be of a universal nature, which, for example, manifests itself in the development of MDD in various somatic diseases, or be specific only for a couple of individual diseases (schizophrenia - breast cancer). At the same time, common genes can have a multidirectional effect, which also contributes to the specificity of comorbidity. In addition, when searching for common genes for somatic and mental diseases, it is necessary to take into account the modulating influence of such confounders as treatment, unhealthy life style, behavioral characteristics, which can also differ in specificity depending on the diseases under consideration.

[Cellular and supracellular models in the study of molecular mechanisms associated with schizophrenia]. / Kletochnye i nadkletochnye modeli v izuchenii molekulyarnykh mekhanizmov, assotsiirovannykh s shizofreniei.

Schizophrenia is a severe mental illness, in the etiology and pathogenesis of which hereditary factors make a significant contribution. Studies of the genetic causes of schizophrenia are conducted using a variety of models. This brief review introduces the reader to cellular and supracellular models that, because of their simplicity, low cost, and low labor intensity, help to effectively investigate the complex molecular mechanisms associated with schizophrenia. The potential of cellular and supracellular models is greatly enhanced by the use of the CRISPR/Cas9 genome editing technology. Genetically modified models make it possible to achieve a previously inaccessible depth and detail of understanding of the role of genetic factors in the onset and development of schizophrenia. The information obtained can be used in the design of new drugs for personalized treatment of schizophrenia patients.

[Molecular-genetic and immunological aspects of the formation of psychopathological symptoms in schizophrenia]. / Molekulyarno-geneticheskii i immunologicheskii aspekty formirovaniya psikhopatologicheskikh simptomov pri shizofrenii.

The authors present the data indicating that the formation of psychopathological symptoms of schizophrenia is due to complex and diverse genetic factors associated with various functional and metabolic pathways at different stages of ontogenesis. Despite the fact that at present the genetic basis of positive and negative symptoms as the main pathophysiological manifestations of schizophrenia remains largely unknown, the current level of research allows the identification of some common and unique associations for positive and negative disorders. Based on the analysis of the literature, the specificity of the association of genetic variants with negative symptoms of schizophrenia is shown. It has been also suggested that genes of the immune system may be specifically associated with negative symptoms of schizophrenia. The relevance of studying the relationship of immune system genes, in particular, pro- and anti-inflammatory cytokines, with dimensional characteristics of negative symptoms (abulia-apathy and expressive deficit) is substantiated. Studies of this type have not yet been conducted, despite accumulating data indicating that the heterogeneity of negative symptoms is based on different neurobiological mechanisms. It is concluded that the immunological and molecular genetic study of the subdomains of psychopathological symptoms can be promising as part of the transition to deep phenotyping, which seems to be especially relevant for the study of such an extremely heterogeneous disease from a clinical point of view as schizophrenia. The development of this area is important for solving the problems of precision medicine, which aims to provide the most effective therapy for a particular patient by stratifying the disease into subclasses, taking into account their biological basis.

[Genetic polymorphism of cytokines IL-1ß, IL-4 and TNF-α as a factor modifying the impact of childhood adversity on schizophrenia symptoms]. / Geneticheskii polimorfizm tsitokinov IL-1ß, IL-4 i TNF-α kak faktor, modifitsiruyushchii vliyanie neblagopriyatnogo detskogo opyta na simptomatiku shizofrenii.

OBJECTIVE: Based on the hypothesis that activation of the immune system is one of the mechanisms of influence of early environmental factors on the onset and course of schizophrenia, we investigated the effects of the interaction of childhood adversity and IL-1ß rs16944, IL-4 rs2243250 and TNF-α rs1800629 polymorphisms on schizophrenia symptomatology. MATERIAL AND METHODS: The sample consisted of 546 patients with schizophrenia spectrum disorders. The presence of childhood adversity was determined based on the analysis of medical records and a questionnaire completed by the patient. We used the 5-factor model of the Positive and Negative Syndrome Scale (PANSS) with the nested two-factor negative syndrome model. RESULTS: After adjusting for multiple comparisons, a significant effect of the interaction of childhood adversity and TNF-α on the cognitive/disorganization factor was found, with a difference between genotypes in the group without childhood adversity (pFDR <0.018; η2p=0.03). A significant effect of the interaction of childhood adversity and genotype on the cognitive disorganization syndrome was established (F=5.87; p=0.003; η2p=0.03). Stereotyped thinking and avolition on PANSS had the highest correlations with cognitive disorganization factor (ro=0.84 and ro=0.82, respectively) and the highest significance of differences depending on the interaction of genotype and childhood adversity (Kruskal-Wallis test, H=12.28, p=0.006 and H=12.79, p=0.005, respectively). CONCLUSION: Childhood adversity modifies the relationship between the pathogenesis of schizophrenia and the TNF-α promoter polymorphism rs1800629, which is also an enhancer of another 60 genes located in the major histocompatibility complex.

[Family history of mood disorders may weaken the link between adverse childhood experience and suicidality in patients with depression]. / Svyaz' semeinoi otyagoshchennosti rasstroistvami nastroeniya s neblagopriyatnym detskim opytom i suitsidal'nost'yu u patsientov s depressiei.

OBJECTIVE: To study the impact of family history of mood disorders (FHMD), comprising genetic factors associated with depression, on the association between adverse childhood experience (ACE) and suicidality in depression. MATERIAL AND METHODS: This multicenter cross-sectional study included 200 in- and outpatients (64% (n=128) women, mean age - (M (SD)) 36.21 (15.09) yrs.) with depression. Self-reports about FHMD and lifetime suicide attempts were obtained in clinical interview. The lifetime intensity of suicidal ideas and behavior was assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS), ACE - by the Adverse Childhood Experience International Questionnaire (ACE-IQ). RESULTS: FHMD did not affect the prevalence of ACE, suicide attempts and C-SSRS scores. We found that FHMD weakens the link between ACE and the risk of suicide attempt. The emotional neglect itself increased the risk of suicide attempt (p=0.001, OR=4.428, CI 95% [1.797-10.911]), but reduced it in patients with FHMD (p=0.03, OR=0.128, CI 95% [0.018-0.893]). GLM analysis revealed that FHMD significantly affected the association between suicidal ideas and domestic violence (p=0.045) and between suicidal behavior and emotional neglect (p=0.015) and abuse (p=0.044). CONCLUSION: FHMD may weaken the link between ACE and suicidality in patients with depression. Suicidality in these patients may be underlined by mechanisms not involved in the response to ACE although more studies are needed.

[Genotype - phenotype relationships in view of recent advances in the understanding of genetic causes of schizophrenia]. / Problema vliyaniya genotipa na fenotip v sovremennykh issledovaniyakh geneticheskikh prichin shizofrenii.

Genotype - phenotype relationships are considered in view of recent advances in our understanding of genome structure. Different DNA elements can contribute to phenotype formation. Genotype - phenotype relationships are mediated by epigenetic effects that can have various origins - from the most studied to date methylation of certain sites in the genome to only developing ideas about the role of remote regulatory genomic elements in the development of schizophrenia. The transition to a more in-depth study of genotype - phenotype relationships is relevant for the current period of molecular-genetic studies of schizophrenia. Obviously, the concept of phenotype as applied to schizophrenia is not limited to a causal reflection of changes in the structure of a particular gene, but is the product of the combined effect of environmental factors and epigenetic changes that affect gene expression, taking into account tissue specificity and the degree of cell stimulation.

[Contemporary GWAS studies of depression: the critical role of phenotyping]. / Sovremennye issledovaniya po polnogenomnomu poisku assotsiatsii pri depressii: kriticheskaya rol' fenotipirovaniya.

The need to use large samples to identify the genetic risk loci of mental disorders has led us to the dilemma of phenotyping quality. Especially this problem relates to such common mental disorders as depression (lifetime prevalence 16.2%). On the one hand, there is a very resource-intensive method of capturing patient data by physicians using diagnostic criteria of mental disorders (DSM-V/ICD-10). On the other, there is a popular method of minimal phenotyping using hospital registers, self-reports of respondents on symptoms, diagnosis and treatment of depression. To date, there is no ideal method for phenotyping depression because all of them focus only on its clinical symptoms. The active usage of minimal phenotyping in Genome-Wide Association Study (GWAS) has led to a significant increase in both clinical and genetic heterogeneity of depression. However, an important limitation of using DSM-V/ICD-10 is the high cost of phenotyping due to the involvement of medical specialists. Thus, the most rational is to use electronic diagnostic questionnaires based on DSM-V/ICD-10 criteria. Such an approach will accelerate the increase in research capacity, but will preserve all internal contradictions inherent in official diagnostic classifications (heterogeneity of phenotypes, absence of objective diagnostic criteria, categorical approach, etc.). In this regard, the critical role of psychiatric epidemiology is growing both in the development of standardized tools for operationalized diagnostic criteria and in future GWAS by introducing new phenotypic subtypes of depression and its dimensions.

Dataset on negative symptoms factors in patients with schizophrenia.

Schizophrenia is a severe mental disorder characterized by positive and negative symptoms. The negative symptoms are highly relevant to the disease course and outcome. Because negative symptoms show considerable heterogeneity, there is substantial interest in elucidating the negative symptom domains that are characteristic of patient subgroups. It has been proposed that patients with schizophrenia should be classified into deficit and non-deficit groups based on the severity of their negative symptoms. Another method suggested the assessment of the factor structure of negative symptoms to understand its mechanisms. Factor analysis of the different negative symptom rating scales reveals two distinct negative symptom subdomains: diminished expression (DE) and avolition/apathy (AA). These characteristics suggest different pathophysiological mechanisms for the development of AA and DE. We present a large dataset of negative symptom factors calculated for 3006 patients with schizophrenia in the Russian population. Sex, age, age at disease onset and data of birth, including season of birth (SOB), family history of schizophrenia are presented. Negative symptoms were assessed with the Positive and Negative Syndromes Scale (PANSS). We calculated negative symptoms factors as suggested by Liemburg et al. (2013). The data will be useful in assessing the impact of such factors as sex, season of birth (SOB) and family history on the scores of negative symptoms subdomains; such data can help us to better understand the heterogeneity of the negative symptoms of schizophrenia.

[Associations between the oxytocinergic system genes, perinatal complications and interpersonal relationships in patients with schizophrenia]. / Issledovanie svyazi mezhdu genami oksitotsinergicheskoi sistemy, perinatal'nymi oslozhneniyami i formirovaniem mezhlichnostnykh otnoshenii u bol'nykh shizofreniei.

OBJECTIVE: To search for the associations between genes of the oxytocinergic pathway and psychosocial functioning in schizophrenia, namely, the ability of schizophrenic patients to form interpersonal relationships, taking into account the influence of such an environmental factor as perinatal complications. MATERIAL AND METHODS: The study included 383 people (140 women and 243 men, mean age 32.6±11.4 years), of whom 107 had a history of perinatal complications, and 276 did not. Psychosocial functioning was assessed using the Personal and social relationships domain of The Personal and Social Performance scale (PSP). Polymorphisms rs53576, rs4686302, rs1042778 in the oxytocin receptor gene (OXTR) and polymorphism rs3796863 in the transmembrane glycoprotein (CD38) gene were genotyped. RESULTS: There is the association between the OXTR rs53576 polymorphism and scores on the interpersonal relations domain (p=0.005). Significant differences are found between carriers of the GG genotype and carriers of the A allele (p=0.003). In the group without perinatal complications, the genotype does not have a significant effect on PSP score. There are no associations between other polymorphisms and the level of interpersonal relationships in any of the studied groups. CONCLUSION: The results are in accordance with the notions accepted on the basis of numerous evidences that link the genes of the oxytocinergic system with social behavior. We obtained new data on the influence of the known polymorphism OXTR rs53576 on the phenotype, which has not been studied previously in this aspect - the ability to form interpersonal relationships in patients with schizophrenia, while it was shown that the effect of the genotype depends on the environmental risk factor (perinatal complications).

[Prognosis of the functional outcome of schizophrenia using a multigene panel]. / Otsenka prognoza funktsional'nogo iskhoda shizofrenii s pomoshch'yu mul'tigennogo testa.

OBJECTIVE: To compare the groups of schizophrenic patients with different levels of functional outcome and different frequency of risk variants in polymorphic loci of five candidate genes to create a multigene panel and to test its predictive ability for long-term outcome of the disease. MATERIAL AND METHODS: According to the proposed typology, the patients included in the studies were divided into three groups, which differed in the level of social functioning. Group 1 was characterized by the highest level, in group 2 this indicator was significantly lower, and in group 3 the lowest. The multigenic panel included genes for serotonin receptor type 2a (5-HTR2A T102C), serotonin transporter (5-HTTLPR), C-reactive protein (CRP -717A>G), angiotensin II receptor type 1 (AGTR1 A1166C), and brain neurotrophic factor (BDNF Val66Met). A multi-gene risk score was calculated for each patient by summing the total number all his/her risk alleles. For each polymorphism, a score of 2 was assigned to homozygous high-risk genotypes, a score of 1 to heterozygous genotypes and a score of 0 to homozygous low-risk genotype. Accordingly, the multi-gene risk score for a patient could vary from 0 to 10 risk alleles. RESULTS: A significant effect of the group on the multi-gene risk score was shown (p<0.0001). Between-group differences were significant as well (p<0.01). In group 1, there were no carriers of ≥6 risk alleles, and the number of carriers of less than 5 alleles exceeded 50%. In group 2, the number of carriers of ≥6 risk alleles was 19.4%, and in group 3 - 31.7%. Moreover, in these groups there were no carriers of 0-2 risk alleles, while in group 1 their number was 20.7%. CONCLUSION: The multi-gene risk score predicts the level of functional outcome in patients with schizophrenia. In the case of a smaller number of risk alleles (0-4) in an individual, a favorable functional outcome can be predicted with a high probability in the long-term period of the disease.

[Family history of affective disorders, the gender factor and clinical characteristics of depression]. / Semeinaya otyagoshchennost' affektivnymi rasstroistvami, gendernyi faktor i klinicheskie kharakteristiki depressii.

OBJECTIVE: Analysis of clinical features of development and course of depression in patients with FH of mood disorders taking into account sex differences. MATERIAL AND METHODS: This multicenter cross-sectional study included patients over 18 years of age with depressive episode/recurrent depressive disorder. Clinical characteristics of depression, presence of comorbid mental illness and family history (FH) information were obtained in a structured clinical interview. RESULTS: One hundred and seventy-one patients (mean age (M (SD)) 40.87 (15.86) y.o.), including 64.5% of women, were enrolled in the study. FH was revealed in 30.2% of patients. The proportion of FH did not differ in men and women (p=0.375). Generalized anxiety disorder (GAD) was more frequent in FH positive patients (p=0.016). Logistic regression also revealed that FH is a risk factor for concomitant GAD (p=0.019, OR=2.4). The GLM demonstrated a significant joint effect of FH and sex on the maximum duration of a depressive episode (p=0.044), as well on the number of suicide attempts (p=0.055) and the number of depressive episodes as a trend (p=0.072). CONCLUSION: We have demonstrated the specific interaction of FH of mood disorders with sex on clinical course of depression. Thus, the manifestation of a genetic influence on the clinical phenotype of depression can be significantly moderated by sex.

[GWAS-based polygenic risk scores for depression with clinical validation: methods and study design in the Russian population]. / Poligennye shkaly riska razvitiya depressii na osnove GWAS s klinicheskoi validatsiei: metodologiya i dizain issledovaniya v rossiiskoi populyatsii.

Depression is one of the leading causes of decreased quality of life and social functioning of patients. In the context of preventive medicine, the prevention of depression becomes a priority. To achieve the goals of prevention, it is necessary to identify specific population risk groups - individuals with a high genetic risk of depression. The paper describes the project aimed at developing a genetic test system based on polygenic risk scores (PRS) for depression, considering the multi-ethnicity and multicultural diversity of the Russian population. As a result of the study, data on the genetic architecture of depression (GWAS) and PRS for depression will be obtained for the first time. The emergence of a genetic test system developed in the study of the Russian population and in the conditions of a constant decrease in the cost of genetic research will allow an effective transition to preventive medicine in the area of mental health.

[Structure of schizotypal traits in the Russian population]. / Struktura shizotipicheskikh chert v rossiiskoi populyatsii.

Establishing the structure of schizotypal traits and its cross-cultural and demographic universality is an important condition for increasing the effectiveness of prognosis of schizophrenic spectrum disorders and basic research on their etiology. The present study aimed to explore the structure of schizotypal traits measured by the Schizotypal Personality Questionnaire (SPQ-74) in the Russian population. Exploratory and confirmatory factor analyses of the factor structure of SPQ-74 were performed using a sample of 1316 people of a wide age range. It is shown that, in the Russian population, the four-factor «paranoid¼ model of N. Stefanis et al. had the best fit for the data. The multivariate confirmatory analysis evidenced the gender invariance of the model.

Copy number variations of satellite III (1q12) and ribosomal repeats in health and schizophrenia.

OBJECTIVE: Earlier we studied the copy number variations (CNVs) of ribosomal repeat (rDNA) and the satellite III fragment (1q12) (f-SatIII) in the cells of schizophrenia patients (SZ) and healthy controls (HC). In the present study we pursued two main objectives: (1) to confirm the increased rDNA and decreased f-SatIII content in the genomes of enlarged SZ and HC samples and (2) to compare the rDNA and f-SatIII content in the same DNA samples of SZ and HC individuals. METHODS: We determined the rDNA CN and f-SatIII content in the genomes of leukocytes of 1770 subjects [HC (N = 814) and SZ (N = 956)]. Non-radioactive quantitative hybridization method (NQH) was applied for analysis of the various combinations of the two repeats sizes in SZ and HC groups. RESULTS: f-SatIII in human leukocytes (N = 1556) varies between 5.7 and 44.7 pg/ng DNA. RDNA CN varies between 200 and 896 (N = 1770). SZ group significantly differ from the HC group by lower f-SatIII content and by rDNA abundance. The f-SatIII and rDNA CN are not randomly combined in the genome. Higher rDNA CN values are associated with higher f-SatIII index values in SZ and HC. The f-SatIII variation interval in SZ group increases significantly in the subgroup with the high rDNA CN index values (>300 copies). CONCLUSION: Schizophrenia patients' genomes contain low number of f-SatIII copies corresponding with a large ribosomal repeats CN. A scheme is proposed to explain the low f-SatIII content in SZ group against the background of high rDNA CN.

[The study of the association between the C677T polymorphism of the methylenetetrahydrofolate reductase gene and severity of symptoms in patients with schizophrenia]. / Izuchenie assotsiatsii geneticheskogo polimorfizma C677T metilentetragidrofolatreduktazy s vyrazhennost'yu simptomov u bol'nykh shizofreniei.

OBJECTIVE: To study the association of the C677T polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene with the risk of schizophrenia in a large sample, including schizophrenic patients and mentally healthy people, and to investigate the relationship of this polymorphism with the severity of schizophrenia symptoms and genotype-environment interaction effects on these symptoms. MATERIAL AND METHODS: The sample for genotyping consisted of 1357 patients with schizophrenia and schizophrenia spectrum disorders and 711 people of the control group. The severity of symptoms was assessed with the PANSS. Obstetrical complications and a traumatic brain injury in medical history were studied as environmental factors. RESULTS AND CONCLUSION: No association was found between MTHFR C677T polymorphism and schizophrenia. There was no genotype effect on the severity of symptoms on the PANSS subscales. The effect of genotype-environment interactions on the severity of schizophrenia symptoms was not detected. The results do not confirm the data of a number of studies on the relationship of MTHFR C677T polymorphism with schizophrenia symptoms.

Effect of VNTR Polymorphism of the AS3MT Gene and Obstetrical Complications on the Severity of Schizophrenia.

The role of the VNTR polymorphism of the AS3MT gene in determining the clinical features of schizophrenia and schizophrenic spectrum disorders was studied. The analysis included 670 individuals. We found no differences in PANSS scores for positive, negative, and common psychopathological symptoms between the carriers of different genotypes. The interaction of the studied polymorphism and obstetrical complications as an environmental factor was found. The genotype-environment interactions were identified for one of the characteristics reflecting the severity of schizophrenia: the level of negative symptoms. Women with the V2/V2 genotype, who have obstetrical complications, showed significantly higher negative symptoms scores, which was associated with a poor prognosis of the disease.

Data on association of the variation (rs1344706) in the ZNF804A gene with schizophrenia and its symptoms in the Russian population.

The polymorphism rs1344706 in the ZNF804A gene is one of the best-supported risk variants for schizophrenia. The association between ZNF804A rs1344706 and the disease was demonstrated in many studies but only few of them investigated large samples (above 2000 patients and controls). Data presented show the genotypic distribution of ZNF804A rs1344706 in 1265 patients with schizophrenia and 1051 healthy controls from the Russian population. Statistical analysis confirmed the association between rs1344706 and schizophrenia (p = 0.034). The frequency of the risk genotype AA was significantly higher in the group of patients compared to that in controls. In addition, the article provides the data on the severity of schizophrenia symptoms measured with the Positive and Negative Syndrome scale (PANSS) in 951 patients. The severity of symptoms was significantly higher in the carriers of the risk genotype AA compared to the AC genotype and the CC genotype.