Objective. To assess associations between polymorphic sites in the TAAR1–9 gene cluster on chromosome 6 and cognitive functions in patients with schizophrenia spectrum disorders and healthy controls. Materials and methods. Patients with schizophrenia spectrum disorders (n = 216) and healthy controls without any family history of mental disorders (n = 240) completed a battery of cognitive tests, which were used to calculate individual indexes of cognitive functioning. Associations between the cognitive index and 22 polymorphic sites in the TAAR genes were assessed by analysis of covariance, controlling for gender, age, the genetic structure of the sample, and polygenic risk scores for schizophrenia and intelligence. Results. A group/genotype interaction at the rs3813355 site in the TAAR5 gene was found to influence the cognitive index (F = 6.68; p = 0.010; η_p^2 = 0.02). Post hoc analysis revealed genotype-related differences in the patients group. Homozygotes for the common A allele had less cognitive deficit than carriers of the minor G allele (t = 2.75; p = 0.032; Cohen’s d = 0.38). The effect of genotype on the cognitive index remained significant when additionally controlling for disease duration and negative symptoms (F = 7.99; p = 0.005; η_p^2 = 0.04). Of the individual cognitive indexes, associations with genotype were found for working memory and attention (F = 8.25; p = 0.005; η_p^2 = 0.05), cognitive flexibility (F = 5.82; p = 0.017; η_p^2 = 0.05), and auditory verbal episodic memory (F = 6.75; p = 0.011; η_p^2 = 0.05). Conclusions. The results obtained here are consistent with the hypothesis that genetic polymorphism of the TAAR5 gene has a role in the variability of cognitive deficit in patients with schizophrenia.

Schizophrenia is a severe psychiatric disease caused by genetic and environmental factors or their interactions that can contribute across multiple disease domains, including negative symptoms (NS), a core feature of schizophrenia. To study the association between season of birth (SOB), a well-replicated risk factor for schizophrenia, and NS domains avolition/apathy (AA) and diminished expression (DE) and to search for an interaction effect of SOB and rs2794521 genetic variants of the inflammatory marker C-reactive protein (CRP) on these domains. The study included 2475 patients with schizophrenia. Patients born during the months of December to February were considered to be winter-born (n = 636) and patients born in other months were considered to be non-winter-born (n = 1839). Genotypes for CRP rs2794521 were obtained for 2437 patients. NS factors were calculated based on the Positive and Negative Syndromes Scale. There was a significant effect of SOB on AA scores (p = 0.009), which remained after adjustment for sex and illness duration. Patients born in winter had higher scores compared with those born in other seasons. No significant effect of SOB on DE scores was observed. An association between the CRP rs2794521 G-allele and AA scores was found (p = 0.044) in the winter-born group, with the carriers of the G-allele having higher scores. There was no effect of the G allele on DE scores in this group and on AA or DE scores in the non-winter group. The results provide new evidence about the effect of SOB and SOB/CRP gene interaction on schizophrenia NS domains.

The MIR137 gene encodes microRNA-137 (miR-137), which is a brain-enriched miR that is highly expressed in various brain regions. miR-137 has been identified as a modulator of processes involved in the pathogenesis of neuropsychiatric disorders. Functional polymorphism of variable number of tandem repeats (VNTR) rs58335419 was found in the regulatory region of the MIR137 gene. It is associated with a change in the expression of miR-137 and, as a result, with an increased risk of developing psychopathologies, including schizophrenia. In this study, we for the first time have analyzed the distribution of frequencies of alleles and genotypes of MIR137 VNTR in a large sample from the Russian population. The association of VNTR with the risk of schizophrenia has been studied. It was found that the presence of VNTR alleles with more than three repeats, as well as a genotype homozygous for such alleles, is associated with an increased risk of developing schizophrenia (OR = 1.4, 95

Background: significant contribution of genetic factors in the development of schizophrenia is a generally recognized fact. Polygenic risk index for schizophrenia turned out to be an effective tool allowing to draw a dividing line between schizophrenia and mentally healthy control in terms of genetics. Objective: to assess the predictive ability of the polygenic risk score for schizophrenia (SZ-PRS) in adolescent patients with a first depressive episode and attenuated psychotic symptoms (APS). Patients and Methods: sixty adolescent inpatient with a first depressive episode were examined. Based on the presence of APS at admission, patients were divided into two groups: a group with APS and a group without APS. Subgroups of patients in the first group were identified through follow-up observations: those with psychosis manifestation and/or low social functioning and those without manifestation and with high social functioning. Whole-genome genotyping was performed for all participants, and SZ-PRS were calculated. For comparison, a group of patients diagnosed with schizophrenia (n = 879) and a group of mentally healthy individuals (n = 759), who had previously undergone whole-genome genotyping and had their SZ-PRS calculated, were used. Results: SZ-PRS of the APS group occupy an intermediate position between the healthy control and schizophrenia patients, significantly differing from each of them. The group without APS did not differ from the control group, but compared to the group of schizophrenia patients, the SZ-PRS in this group was significantly lower. Comparing subgroups of patients showed that the SZ-PRS in the APS group without psychosis manifestation and social functioning impairment was significantly lower than in the group with schizophrenia manifestation. The APS subgroups with psychosis manifestation and with functioning impairment did not differ significantly from each other or from the schizophrenia group. Conclusion: the results obtained for the first time for the russian population showed that SZ-PRS can be considered as a tool for assessing the risk of developing psychosis or reduced social functioning in patients with APS.

It is known that the neurohormone oxytocin plays an important role in the pathogenesis of mental illness and also models the relationship between stress factors, especially those acting in the early stages of development, and the development of mental disorders. On the basis of these data, we investigated the effects of the interaction of the environmental factor, in the capacity of which the childhood adversity (CA) and the oxytocin receptor (OXTR) genotypes in the polymorphic sites rs4686302 and rs7632287 were considered, on the severity of negative symptoms of schizophrenia. The study involved 592 patients with schizophrenia (code F20, according to ICD-10). Information about the presence of CA was obtained from case histories and patient interviews. Analysis of covariance (GML) was used for statistical data processing; in post hoc pairwise comparison, Tukey’s test was used. A significant effect of the interaction between CA and OXTR gene polymorphism rs7632287 (G/A) on the severity of negative symptoms in patients with schizophrenia was revealed. In patients without CA, polymorphisms did not have a significant effect on the studied phenotype. Thus, our study showed for the first time that the rs7632287 (G/A) polymorphism and CA have a mutual effect on the severity of negative symptoms of schizophrenia.

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.

The study attempted to test experts' assumptions about the difference in the genetic mechanisms of the formation of emotional and volitional deficits in schizophrenia with predominance of negative disorders. The aim of the study is to create empirical theory of these two phenomena using an approach based on JSM-method for automated research support (JSM-method ARS). Polymorphisms of four genes associated with schizophrenia (BDNF, 5HTR2A, HTTLPR, ZNF804A) and clinical data presented as PANSS score were used as empirical data. The use of generalized JSM-method ARS, which generates ternary relationships “cause-blocker-effect”, allows us considering in detail the interaction of specific gene variants for emotional and volitional deficits in negative schizophrenia. The result of the study is confirmation of the experts' hypothesis about the difference in the mechanisms of these clinical manifestations. This conclusion was based on a comparison of knowledge fragments for two phenomena. The utilized approach can be extrapolated to a larger number of genes. We suggest that the use of the generalized JSM-method ARS is a promising approach to studying gene interactions in schizophrenia.

Research suggests that, in contrast to circulating C-reactive protein (CRP), genetic variants conferring higher CRP levels have protective effects against schizophrenia and moderate influences of season of birth on the development of the disease. This study aimed to explore whether the CRP gene also moderates the relations between childhood adversity and clinical characteristics of schizophrenia. The relations between childhood adversity, genotypes at rs2794521 within the CRP locus, syndromes measured as five factors and two negative subfactors of the Positive and Negative Syndrome Scale, and history of suicide attempts were analyzed in 921 schizophrenia patients. A significant effect of genotype on suicide attempts in patients exposed to childhood adversity was found. The result suggests a moderating role of genetic determinants of inflammation in translating early life psychological stress effects into risk of suicide attempts in schizophrenia.

The AS3MT gene encodes arsenic(III) methyltransferase. VNTR polymorphism of the AS3MT gene is characteristic only for the human genome. It is associated with the expression of a human-specific AS3MTd2d3 protein isoform, which is a potential risk factor for the development of schizophrenia. In this study, we for the first time have analyzed the distribution of frequencies of alleles and genotypes of VNTR polymorphism in a large sample of ethnic Russians. The association of VNTR with the risk of schizophrenia has been studied. The study included 1002 patients with schizophrenia and schizophrenia spectrum disorders and 1510 people of the control group. Women with the V3/V3 genotype have an increased risk of schizophrenia (OR = 1.4, 95% CI: 1.11–1.77).

Objectives . Working from the hypothesis that activation of the immune system is one of the mechanisms whereby early environmental factors influence the onset and course of schizophrenia, we studied the effects of the interaction of adverse childhood experiences (ACE) and genotypes at the polymorphic loci rs16944 of the IL1B gene, rs2243250 of the IL4 gene, and rs1800629 of the TNF - α gene on the severity of different groups of schizophrenia symptoms. Materials and methods . The cohort consisted of 546 patients with schizophrenia spectrum disorders. ACE was detected by analysis of medical records and a questionnaire completed by the patients. A five-factor Positive and Negative Syndrome Scale (PANSS) model with a built-in two-factor model of the negative syndrome was used. Results . The interaction of ACE and TNF - α was found to have a significant effect on the cognitive disorganization factor after adjusting for multiple comparisons, with discrimination of carriers of different genotypes in the group without ACE ( p FDR < 0.018; _p^2 = 0.03). The interaction of ACE and genotype was found to have a significant effect on the cognitive disorganization syndrome (F = 5.87; p = 0.003; _p^3 = 0.03). Stereotyped thinking and volitional disorder identified on the PANSS showed the strongest correlations with the cognitive disorganization factor ( r o = 0.84 and r o = 0.82, respectively) and the most significant differences depending on the interaction of genotype and ACE (Kruskal–Wallis test, H = 12.28, p = 0.006 and H = 12.79, p = 0.005, respectively). Conclusions . ACE modifies the relationship between the pathogenesis of schizophrenia and the rs1800629 polymorphic locus located in the TNF-α gene promoter, which is also an enhancer of 60 more genes located in the major histocompatibility complex.

We studied the relationship between the ZNF804A rs1344706 gene polymorphism and the parameters of event-related synchronization/desynchronization of EEG rhythms in visual perception of semantic and meaningless verbal information in patients with schizophrenia and schizophrenia spectrum disorders (n = 93) and mentally healthy subjects (n = 93). When reading verbal information regardless of psychiatric status, the theta rhythm synchronization was less pronounced in subjects with the AA genotype than in carriers of allele C. In healthy subjects, the carriers of the AA genotype, in comparison with carriers of allele C, the synchronization of theta rhythm in the posterior cortical areas of the left hemisphere was reduced, and there were no differences in the synchronization of gamma and desynchronization of mu rhythms when perceiving semantic and nonsensical verbal information. In patients with genotype AA, compared with carriers of allele C, the desynchronization of mu rhythm was smaller, which correlated with the severity of poverty of speech on the PANSS scale. The study results indicate a modulating effect of the rs1344706 polymorphism of the ZNF804A gene on the neurophysiological characteristics of the reading process and its contribution to the variability of clinically expressed language disorders.

В сообщении представлены данные молекулярно-генетических исследований, показывающие специфичность связи вариантов генов иммунной системы с негативными симптомами шизофрении, в частности ассоциации генов про- и противовоспалительных цитокинов с дименсиональными характеристиками негативных симптомов (факторы абулия-апатия и экспрессивный дефицит). Исследования такого типа до сих пор не проводились, несмотря на накапливающиеся данные, указывающие на то, что в основе гетерогенности негативных симптомов лежат разные нейробиологические механизмы. Иммунологическое и молекулярно-генетическое исследование субдоменов психопатологических симптомов может быть перспективным в рамках перехода к глубокому фенотипированию, которое представляется особенно актуальным для изучения такого крайне гетерогенного с клинической точки зрения заболевания, как шизофрения. Развитие этого направления важно для решения задач точной медицины, ставящей своей целью обеспечение наиболее эффективной для конкретного пациента терапии путем стратификации заболевания на подклассы с учетом их биологической основы.

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.

Введение. Шизофрения относится к заболеваниям, отличающимся значительной гетерогенностью симптомов. В полной мере это относится к негативным симптомам (НС), гетерогенность которых, согласно современным представлениям, определяют различные нейробиологические механизмы. В настоящее время распространение получила модель, предусматривающая выделение в структуре НС двух факторов (субдоменов): абулии-апатии (АА) и экспрессивного дефицита (ЭД). Иммунологические исследования показали, что концентрация провоспалительного цитокина ФНО-α дифференцированно связана с субдоменами НС. Цель: исследовать связь между факторами НС и полиморфизмом rs1800629G/A гена ФНО-α. Методы. Выборка для генотипирования составила 541 человек. Выраженность НС определяли по шкале позитивных и негативных синдромов (PANSS). Симптомы шкалы PANSS включали в субдомены в соответствии с ранее предложенным подходом. Генотипы определяли методом ПЦР. Результаты. Выявлены различия в выраженности симптомов ЭД в зависимости от генетического варианта rs1800629 (р=0,035). У пациентов с двумя копиями аллеля А, обладающего более высокой транскрипционной активностью, выраженность симптомов ЭД была выше, чем у носителей аллеля G (22,8±4,7 против 19,2±5,9 балла). Не обнаружено значимого эффекта генотипа на фактор АА. Заключение. Обнаружение дифференцированной связи полиморфизма rs1800629 гена ФНО-α с НС шизофрении находится в соответствии с данными иммунологических исследований, а также подтверждает предположение о различных биологических механизмах, определяющих гетерогенность НС шизофрении. Background. Schizophrenia is characterized by a significant heterogeneity of symptoms. This fully applies to negative symptoms (NS), the heterogeneity of which, according to modern concepts, is determined by various neurobiological mechanisms. A widespread model of NS provides two factors (subdomains) in the structure of NS: abulia-apathy (AA) and expressive deficit (ED). Immunological studies have shown that the concentration of the pro-inflammatory cytokine TNF-α is differentially associated with NS subdomains. Objective. To investigate the relationship between NS factors and the TNF-α polymorphism rs1800629G/A. Methods. The sample for genotyping included 541 people. The severity of NS was determined by the Positive and negative syndromes scale (PANSS). PANSS symptoms were included into subdomains in accordance with the previously proposed approach. Genotypes were determined by PCR. Results. Differences in the severity of symptoms of the ED factor depending on the genetic variant rs1800629 were revealed (p=0.035). In patients with two copies of the A allele, which has a higher transcriptional activity, the severity of ED symptoms was higher than in the G allele carriers (22.8±4.7 versus 19.2±5.9 points). No significant effect of genotype on factor AA was found. Conclusion. The discovery of a differentiated relationship between TNF-α rs1800629 polymorphism and NS is consistent with the data of immunological studies, and also confirms the assumption of various biological mechanisms that determine the heterogeneity of schizophrenia NS.

Objectives. To identify any relationship between the genes of the oxytocinergic pathway and psychosocial functioning in schizophrenia, i.e., the ability of schizophrenia patients to form interpersonal relationships, taking account of the influence of environmental factors such as perinatal complications. Materials and methods. The study involved a total of 383 people (140 women and 243 men, mean age 32.6 ± 11.4 years), of whom 107 had perinatal complications and 276 did not. Psychometric studies used a points assessment of the level of social functioning (the interpersonal relationships domain of the Personal and Social Performance Scale (PSP)). Genotyping addressed the rs53576, rs4686302, and rs1042778 polymorphisms in the oxytocin receptor gene ( OXTR ) and the rs3796863 polymorphism of the transmembrane glycoprotein gene ( CD38 ). Results. The group with perinatal complications showed an association with OXTR polymorphism rs53576 and the level of interpersonal relationships ( p = 0.005). Significant differences were found between carriers of the GG genotype (rs53576) and carriers of the A variant ( p = 0.003). In the group without perinatal complications, the genotype did not show any significant effect on this parameter. Other polymorphic sites showed no association with the level of interpersonal relationships in either group. Conclusions. The results obtained here are consistent with concepts based on extensive evidence linking oxytocinergic system genes with social behavior. We obtained new data on the influence of the known OXTR polymorphism rs53576 on a phenotype not previously studied from this point of view – the ability to form interpersonal relationships – in schizophrenia patients; the genotype effect was found to depend on the environmental risk factor (perinatal complications).

Шизотипию рассматривают как фенотип, отражающий доклинические проявления генетической предрасположенности к шизофрении. Существует два взгляда на природу этой связи - дименсиональный и таксономический. Предыдущие исследования вклада полигенных показателей риска (PRS) шизофрении в выраженность шизотипии были проведены в западноевропейских популяциях, использовали дименсиональную модель и получили отрицательные результаты. Цель настоящего исследования заключалась в оценке связи PRS шизофрении с дименсиями и таксонами шизотипии в русской популяции. Методы. Полногеномные данные были получены для выборки из 290 здоровых испытуемых, принадлежащих к кластерам лиц с низкой, позитивной, негативной и высокой смешанной шизотипией. Шизотипию измеряли с использованием Опросника шизотипической личности (SPQ). Результаты. PRS шизофрении не коррелировали с когнитивно-перцептивным, параноидным, межличностным или дезорганизационным дименсиями SPQ. Таксоноподобные группы (кластеры) различались по PRS на уровне тенденции с максимальными PRS в группе с высоко выраженной смешанной шизотипией. Заключение. Результаты согласуются с предположением таксономической модели о том, что у части здоровых лиц с высокой выраженностью шизотипических личностных черт последние являются отражением генетической предрасположенности к шизофрении. Schizotypy is considered as a phenotype that reflects preclinical manifestations of a genetic predisposition to schizophrenia. There are two views on the nature of this relationship - dimensional and taxonomic. Previous studies on the contribution of schizophrenia polygenic risk scores (PRS) to schizotypy were conducted in Western European populations using the dimensional model and yielded negative results. The objective of this study was to assess the relationship between schizophrenia PRS and dimensions and taxa of schizotypy in the Russian population. Methods. Genome-wide data were obtained from a sample of 290 healthy subjects belonging to the clusters of individuals with low, positive, negative, and high mixed schizotypy. Schizotypy was measured using the Schizotypal Personality Questionnaire (SPQ). Results. The schizophrenia PRS did not correlate with cognitive-perceptual, paranoid, interpersonal, or disorganized SPQ factors. Taxon-like groups (clusters) differed in PRS at a trend level, with the highest PRS being found in the high mixed schizotypy group. Conclusion. The results are consistent with the assumption of the taxonomic model of schizotypy that in some healthy individuals with a high degree of schizotypal personality traits, these traits reflect the genetic predisposition to schizophrenia.

В последние десятилетия особое внимание при изучении шизофрении уделяется особенностям распознавания эмоций и влияния как генетических так и средовых факторов на развитие индивида и риск развития психических заболеваний. Существует предположение, что нарушения распознавания эмоций являются одним из эндофенотипов заболевания. Установлена важная роль нарушения социальных когниций, и, в частности, распознавания эмоций, в социальной адаптации больных шизофренией. Установление роли генетических и средовых факторов риска шизофрении в этих нарушениях является важным шагом к формированию терапевтических подходов к их коррекции. Цель - оценить связь полиморфизма rs1344706 гена ZNF804A и неблагоприятной среды в детстве (наличия алкоголизма в родительской семье) на распознавание эмоций у больных. Методы. Выборка состояла из 854 больных, разделенных на две группы: с алкоголизмом в родительской семье и без него. Для оценки распознавания мимической экспрессии эмоций использовали фотографии шести базовых и трех социальных эмоций. Генотипирование проводили методом HRM. Результаты. Обнаружен эффект взаимодействия между генетическим вариантом ZNF804A (rs1344706) и злоупотреблением алкоголем одним из родителей пробанда на нарушение распознавания эмоций (p=0,02). Больные с генотипом АА хуже распознавали эмоции, чем больные с генотипом СС. Заключение. Результаты позволяют предположить важную роль взаимодействия генов риска шизофрении, связанных с нейроразвитием, и ранних средовых стрессоров в аномалиях социальных когниций при шизофрении. Background. In recent decades, special attention in the study of schizophrenia has been paid to the features of emotion recognition and the influence of both genetic and environmental factors on the development of the individual and the risk of developing mental illness. There is an assumption that disorders of emotion recognition are one of the endophenotypes of the disease. The important role of the violation of social cognitions, and in particular the recognition of emotions, in the social adaptation of patients with schizophrenia has been established. Establishing the role of genetic and environmental risk factors for schizophrenia in these disorders is an important step towards the formation of therapeutic approaches to their correction. Aim - to assess the contribution of the rs1344706 polymorphism of the ZNF804A gene and an unfavorable environment in childhood (the presence of alcoholism in the parental family) to the recognition of emotions in patients. Methods. The sample consisted of 854 patients divided into two groups: with alcoholism in the parental family and without it. To assess the recognition of mimic expression of emotions, photographs of six basic and three social emotions were used. Genotyping was performed by the HRM method. Results. An interaction effect between the genetic variant ZNF804A (rs1344706) and alcohol abuse by one of the proband’s parents on impairment of emotion recognition was found (p=0.02). Patients with the AA genotype were worse at recognizing emotions than those with the CC genotype. Conclusion. The results suggest an important role for the interaction of neurodevelopmentally associated schizophrenia risk genes and early environmental stressors in social cognition anomalies in 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.

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-1β 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.

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).