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The negative impact of depression on the course and outcome of somatic disorders is well-known and has a solid theoretical basis. The analyses of prospective studies confirm the role of depression as an independent and significant risk factor for widespread chronic somatic disorders including such severe and life-threatening conditions as cardiovascular diseases, diabetes and oncological pathology. The majority of somatic disorders and depression are the part of the big class of hereditary diseases with multifactorial character and polygenic nature. It is likely, that the genetic risk diversity of these diseases in population is close. There is also a high probability of genetic risks levels overlap (or of common «cluster») of two or more diseases in one individual, with one disorder being major depression. In that case such diseases could be considered «genetically comorbid» and manifestation of one disease could alter the risks of other. Precise and informative diagnostic tools could detect subsyndromal depression that could be the prognostic sign of the high risk and rapid manifestation of somatic diseases. Thus, patients with depressive disorder could be considered as a group with high risks of diverse range of somatic pathology. The coalescence of fundamental biomedical scientists and internists (psychiatrists and other physicians) could lead to the elaboration of specific complex preventative measures including social ones.

The high prevalence of primary affective disorders in patients with epilepsy is beyond doubt. However, patients in this group are often identified as suffering from mood disorders that do not fulfil the criteria for primary mood disorders, such as recurrent depressive disorder and bipolar affective disorder. The aim of this paper is to analyze the classification and clinical picture of affective disorders in patients with epilepsy and differential diagnostic approaches to identify primary affective disorders and secondary affective disorders in epilepsy. A set of diagnostic signs for the differential assessment of affective disorders in patients with epilepsy is presented. Research of affective pathology in patients with epilepsy and the development of strategies for its successful treatment are still needed.

To date, inflammatory mechanisms are known to be involved in neuronal damage and increased risk of associated mental disorders, but most previous work has focused primarily on cytokines and other inflammatory markers that are difficult to replicate and not economically feasible for use in routine clinical practice. Other extremely important indicators of the systemic inflammatory process are circulating blood cells and changes in their number, composition, and ratio. Hematologic indices of systemic inflammation (HISI) are already used in somatic specialties: neutrophil-lymphocyte (NLR), monocyte-lymphocyte (MLR) and platelet-lymphocyte (PLR) ratios, as well as the Systemic Immune Inflammation Index (SII) and the System Inflammation Response Index (SIRI). In the context of psychopathology, the HISI require additional investigation, which makes it necessary to pay more attention to the possible mechanisms underlying their changes. The article provides data on the contribution of each cellular element to the mechanism of neuroinflammation and neurodegeneration and on their role in the development of psychopathological processes.

The introduction of information technologies is inextricably linked with improving the quality and accessibility of medical care, as well as reducing the cost of medical services. Digital phenotyping is one of the clinical tools in the field of information technology that allows you to evaluate a person’s phenotype using various personal information devices, such as a smartphone, tablet, smartwatch, various sensors and other computer tools. The advantage of digital phenotyping is the ability to receive information about the patient’s condition in real time, without inpatient and outpatient monitoring and even without the active participation of the patient himself. This fact significantly expands the possibilities of screening and diagnosis of mental disorders, and also helps to track the risks of relapses and take timely measures to prevent an exacerbation of the disease. Information technologies have great prospects for use for scientific purposes — they provide an opportunity to conduct research online that does not require visiting research centers, while at the same time reducing the time and costs of ongoing clinical trials. However, the use of digital phenotyping for scientific and clinical purposes has a number of limitations. For further improvement of digital phenotyping in order to screen psychopathology and subsequent assessment of the condition of patients, it is necessary to develop new psychometric tools used in electronic form and devoid of the shortcomings of questionnaires that are currently being used. This critical review provides data on the current opportunities and problems of digital phenotyping, as well as the prospects for its development.

Introduction: Currently, there is a large amount of data that inflammatory and oxidative stress biomarkers, pterin metabolism disturbances and other biochemical abnormalities are more often present in schizophrenia compared to general population. They may also play the role of etiopathogenetic factors in schizophrenia mechanisms. At the same time, there are no studies with an assessment of a wide range of correctable biochemical abnormalities in one sample of patients. Moreover, screening algorithms for the detection and personalized correction of controlled biomarkers have not been introduced into clinical practice yet. The aim of this work was to evaluate the prevalence of significant etiopathogenetic biochemical disturbances in patients with schizophrenia in order to justify the need for biochemical screening and correction of the corresponding abnormalities. Materials and methods: in the blood serum of 125 patients with schizophrenia and 95 healthy volunteers the levels of folate and cobalamin (B12) (chemiluminescent immunoassay on microparticles), homocysteine (HC, enzymatic analysis), tetrahydrobiopterin (BH4, competitive enzyme immunoassay, ELISA), reduced glutathione (GSH, spectrophotometry with Ellman’s reagent), interleukin-6 (IL-6, ELISA based on a three-stage «sandwich version») and C-reactive protein (CRP, immunoturbodimetric method) were evaluated. Results: In patients with schizophrenia the level of all studied serum biochemical markers, except for B12, was significantly different compared to healthy volunteers. The deviations levels of the studied parameters from the reference values in patients were statistically significantly higher in the markers of pterin metabolism (VH4: p = 0.0000; folates: p = 0.0000; HC: p = 0.0094). 29.6 % of patients were carriers of 4 or more studied biochemical abnormalities, while among healthy volunteers this occured in 5.3 % of cases (Xi2 = 19.2; p < 0.001). Conclusion: The results obtained raise the question for the need of monitoring principles for a number of biochemical markers in schizophrenia and their implementation in clinical practice.

The article is devoted to modern concepts of cognitive disorders in schizophrenia. Neurocognitive deficits can be expressed in impaired attention, auditory memory, motor skills, working memory, processing speed and executive function. The attention of researchers is currently being paid to the violation of the speed of information processing and character encoding that can lead to impaired social functioning in patients with schizophrenia. Two hypotheses about the dynamics of neurocognitive impairments in schizophrenia are also considered: the theory of «static encephalopathy» and progressive impairment of cognitive functions.This review evaluates the results of a comparative analysis of the effectiveness of first and second generation antipsychotics in the treatment of cognitive dysfunction. As a result of the analysis of the available data, it was concluded that first-generation antipsychotics most likely do not directly impair cognitive abilities, but they can do so indirectly, due to the simultaneous use of anticholinergic drugs that compromise some neurocognitive abilities. Second-generation antipsychotics have an advantage over first-generation drugs, however, it has been argued that most antipsychotics lead to a slight improvement in cognitive functioning, and there is no specific effect on its specific domains.An analysis of data on the relationship between oxidative stress markers and psychopathological characteristics and cognitive profile of patients with schizophrenia was carried out. In particular, the mechanism of stress-induced cell death in the prefrontal and anterior frontal regions and a decrease in brain volume in these regions, leading to a decrease in cognitive and executive functions, are considered. In addition, the mechanisms of association of redox imbalance with brain-derived neurotrophic factor (BDNF) depletion, hypofunction of the NMDA receptor, changes in the level of pro-inflammatory cytokines, neurogenesis, and cell apoptosis were considered.

Interleukin-6 (IL-6) is one of the most important pro-inflammatory markers with immunomodulatory activity associated with schizophrenia. The possible involvement of interleukin-6 in the etiopathogenesis of schizophrenia and the development of different clusters of symptoms remains debatable; the relationship between an increase in interleukin-6 and a number of possible confounding factors, including smoking, has not yet been studied. The aim of this work was the pilot evaluation of the serum IL-6 level in patients with schizophrenia compared with healthy controls, as well as its association with clinical symptoms, socio-demographic factors and smoking. Materials and methods: 43 patients with schizophrenia and 24 healthy volunteers were examined. The determination of IL-6 was carried out by enzyme immunoassay. All patients were assessed using the Positive and Negative Schizophrenia Syndrome Scale (PANSS), The UKUSERS-Clin Therapeutic Side Effects Scale (UKU), Simpson-Angus Scale (SAS), the Abnormal Involuntary Movements Scale (AIMS), Barnes Akathisia Scale (BARS), Personal and Social Functioning Scale (PSP). Results: In patients with schizophrenia in a Russian sample, serum IL-6 levels were significantly associated with smoking status (p = 0.0017), the severity of negative symptoms and symptoms of the PANSS general psychopathology scale (p=0.014 and p=0.038, respectively), disorders of personal and social functioning (PSP, p=0.011), as well as side effects measured using the UKU scale (general, p=0.038, 0041 and extrapyramidal, p=0.018), as well as drug-induced parkinsonism (p=0.043), dyskinesia (p=0.0084) and akathisia (p=0.043). All scores are worse in patients with nicotine addiction. The occurrence of extrapyramidal symptoms (EPS) in response to standard doses of antipsychotics (AP) can serve as a clinical marker of possible immune-inflammatory disturbances in patients with schizophrenia, and the smoking status can act as a provocing factor for increasing of latent inflammation. Replication of the study is required to confirm the findings.

Antipsychotics (AP) administration in schizophrenia patients is associated with several side effects (SE), in particular, with extrapyramidal (EP). Data suggests that oxidative damage to dopaminergic neurons in the EP system may be related to tardive dyskinesia and Parkinson's disease (PD) development, although data on the role of oxidative stress in the development of early EPSE of AP is lacking. Another poorly studied hypothesis of the EP-symptoms pathogenesis considers disorders of folate (pterin) metabolism.Objective: to evaluate the relationship between redox imbalance and pterin metabolism with the severity of early EPSE caused by AP used in the schizophrenia treatment.Patients and methods. The study included 50 patients with the first episode of schizophrenia. EP symptoms were evaluated using the UKU Side-Effect Rating Scale (“UKU-SERS-Clin” version). The levels of reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), aldehyde-2,4-dinitrophenylhydrazone, ketone-2,4-dinitrophenylhydrazone were assessed in blood plasma; levels of BH4, folate, cobalamin (vitamin B12), and homocysteine – in blood serum; superoxide dismutase (SOD) and catalase activity – in erythrocytes.Results and discussion. EPSE severity was inversely proportional inversely proportional to the GSH level and directly proportional to the SOD activity. EPSE severity was also associated with AP selectivity, but not with their dosages. However, AP selectivity was not associated with studied biochemical parameters. MDA level in patients prescribed with amantadine was lower than in other participants.Conclusion. Early AP-induced EPSE were associated with redox imbalance, which indicates the necessity for further research aiming at prevention of secondary neurodegenerative diseases in patients with schizophrenia receiving AP.

Introduction Non-suicidal self-injury (NSSI) – the deliberate, self-directed damage of body tissue without suicidal intent and for purposes not socially or culturally sanctioned – is a highly prevalent phenomenon in adolescents and young adults. Motivation for the NSSI is known to be heterogenous in different patients. However, biological and especially genetic markers associated with different motivation for the NSSI have not been studied to date. One of the possible candidates are mu- (OPRM1) and kappa-opioid receptor (OPRK1) genes, since opioid system is known to be involved in the NSSI. Another perspective candidate is the DCC gene, encoding the netrin 1 receptor, which plays vital part in the formation of the prefrontal cortex. Objectives We conducted a pilot cross-sectional study to test the impact of the rs1779971 OPRM1, rs6473797 OPRK1 and rs8084280 DCC gene polymorphisms on the characteristics and motivations for the NSSI in young adults. Methods 28 patients of European ancestry with NSSI (89,3%; n=25) women, median age (Q1-Q3) – 23 (21,25-25) years) were included in the pilot sample. The majority of the sample had a diagnosis of bipolar disorder (78,6%; n=20). Characteristics and motivation for the NSSI were measured by the Inventory of Statements about Self-Injury (ISAS). The Childhood Trauma Questionnaire (CTQ) was used to control for adverse childhood experiences, a potent environmental factor, associated with NSSI. Genotyping was performed using RT-PCR. The genetic effect was evaluated using the dominant model. For statistical analysis multiple linear regression with the presence of minor alleles, different types of childhood trauma, diagnosis, age and sex as factors and ISAS scores as dependent variables were used. Results Multiple linear regression showed that minor C allele of rs6473796 OPRK1 gene polymorphism was associated with an increase of the “Affect regulation” (B=2,23; CI95% [0,39–4,06]; p=0,022), “Anti-dissociation” (B=3,31; CI95% [0,18–6,44]; p=0,039) subscales of ISAS scores. Moreover, the minor T allele of the rs8082480 DCC gene polymorphism was associated with a decrease of the “Affect regulation” subscale score (B=-1,74; CI95% [-3,30 – -0,18]; p=0,032). Conclusions To our knowledge, this is the first study on the genetic markers of motivations for NSSI. Our pilot results showed that, controlling for diagnosis, age, sex and childhood trauma, OPRK1 and DCC gene polymorphisms may be associated with the heterogeneity of motivations for NSSI. However, these results require confirmation on the larger samples. Disclosure of Interest None Declared

Currently, a growing amount of data is emerging on the role of various environmental factors (nutrients, gut microbiota, etc.) on formation of depression. The impact on these factors can be effective not only in treatment of major depressive disorder, but also in its early prevention. Therefore, a more detailed study of environmental factors in depression can lead both to a better understanding of the etiology and pathogenesis of the disorder and to optimization of approaches to its treatment. The aim of the review was to assess the potential role of a number of environmental factors associated with nutritional aspects and characteristics of individual microflora, as well as to review the prospects of a strategy for affecting these factors in treatment and prevention of depression.

Despite the emergence of new antidepressants with different mechanisms of action, a large number of problems in antidepressant therapy remain. Considering the known antimicrobial activity of antidepressants, the role of the microbiota in the thymoanaleptic activity of these drugs is of high interest. In recent years, important data have been obtained on the role of the gut microbiota in the regulation of behavior and the pathophysiology of a number of mental disorders, including depression. Of particular interest is the assessment of the normal intestinal microbiota role in the course of the therapeutic process. The emerging bi-directional interactions between drugs and microorganisms may be critical for personalized drug selection and future drug development. However, at the present time, this problem remains poorly understood. The proposed manuscript articulates the main directions that are of clinical importance and can become an object for further study in this area.The research results indicate that the effect of antidepressants on the microbiota is a promising area, the study of which could provide many important findings for clinical practice. This type of therapeutic manipulation can provide an opportunity for intervention in order to potentiate the activity of antidepressants or to minimize side effects. The problem with this method of intervention is enormous complexity, when manipulations can have both positive and negative effects simultaneously, depending on different strains of microorganisms influencing different therapeutic effects. More research is needed to understand what changes occur in the microbiome with acute and chronic administration of specific antidepressants. Perhaps this will contribute to the development of microbiomodulatory tactics for individualized interventions.

Threats to life and health, the public health crisis associated with the COVID-19 pandemic, have led to 1) accelerated development of vaccines, 2) adverse psychological reactions in the population.Aim: to identify differences in stress, anxiety, protective behavior strategies, and the socio-demographic characteristics of online survey participants, who reported opposing attitudes to SARS-CoV-2 vaccination.Materials and Methods. In December 2020-January 2021, 131 respondents were assessed (men—21.4%). The Psychological Stress Scale (PSM 25), original questionnaires to evaluate pandemic concerns and protective behavior strategies with special question about COVID-19 vaccine acceptance were used. Effect sizes obtained using Cohen’s d and Cramer’s V measures were calculated for groups, the differences between which were significant (p≤0.05).Results. A 47.3% sample, having PSM-25 rates above the threshold (100 points), showed a distress reaction to the pandemic due to anxiety stress. Compared to the spring of 2020, the number of concerns associated with a noticeable stress growth (ES≥0.34) increased from two to six. Psychological distress, concerns about the possible lack of medication for daily intake, harsh social consequences and self-isolation were associated with only foreign producer vaccine acceptance (ES=0.3-0.5). Absence of excessive fears for own life, concerns about the lack of personal protective equipment and unacceptance of gloves as a measure to prevent infection (ES=0.3-0.4) were important factors associated with any producer vaccine acceptance. Men, comparing to women, were more positive in vaccine acceptance.Conclusion. The anxiety distress is an important factor in the rational attitude to coronavirus infection vaccine.

Summary. Tetrahydrobiopterin (BH4) is an important cofactor, that involved in the synthesis of dopamine, norepinephrine, and serotonin, as well as affecting the production of nitric oxide (NO) and regulating the activity of the glutamatergic system. A few foreign studies have shown, that patients with schizophrenia had a markedly reduced level of BH4 compared to the healthy population. The aim of this work was to study the association of BH4 deficiency with the risk of schizophrenia among Russian patients by comparison with a group of healthy volunteers.Materials and methods: 50 patients with schizophrenia and 36 healthy volunteerswere randomly selected and underwent a biochemical study of the BH4 level using the method of competitive enzyme immunoassay (ELISA) on a spectrophotometer (Sunrise, Tecan) with a set of CEG421Ge (CloudClone Corp).Results: it was found that the BH4 level was significantly lower in patients than in the controlgroup (3684.75 [1283.00; 4815.00] versus 4260.60 [4057.40; 5236.85] pmol / l, respectively, p = 0 , 0016). The proportion of patients with a BH4 level below the lower limit of the interquartile range in healthy volunteers (4057.40 pmol / l) is 30/50 (60%), the proportion of healthy volunteers with a BH4 level below this border is 9/36 (25%), the difference is statistically significant, χ2 = 10.35; p = 0.002; OR = 4.5; 95% CI [1.75; 11.56](CI — confidence interval). The correlation of BH4 level with the duration of the disease, gender, age of the subjects is very weak and not statistically significant.Conclusion: further interdisciplinary studies are required to identify the causes and molecular mechanisms for the development of BH4 deficiency in schizophrenia and to develop approaches to personalized pharmacological intervention.

Personalized medicine means the selection of therapy for patients, taking into account the assessment of genetic risk factors for side effects. A number of studies show that folate metabolism disorders, including single nucleotide polymorphisms (SNPs) in the genes of folate-metabolizing enzymes, are more frequently detected in schizophrenic patients than in the general population. The role of SNPs of the key folate cycle enzymes in developing the extrapyramidal side effects of antipsychotics has not yet been studied, although there is evidence of their association with other movement disorders.Objective: to analyze the association between the carriage of SNP alleles of MTHFR 677C>T, MTR 2756A>G, and MTRR 66A>G and the severity of extrapyramidal side effects of antipsychotics in patients with schizophrenia.Patients and methods. The investigation included 61 patients with schizophrenia (according to the criteria for ICD-10 Code F20). All the patients took antipsychotics for at least 7 hospital days were examined using real-time polymerase chain reaction (PCR) with allele-specific primers, followed by detection for the carriage of SNP alleles of MTHFR 677C>T, MTR 2756A>G, and MTRR 66A>G. The standardized Simpson–Angus scale (SAS) was used to evaluate the severity of extrapyramidal symptoms; the PCR test results were unknown during their examination.Results and discussion. In the patients carrying a low-functional 677 T allele in the gene of the key folate cycle enzyme MTHFR, the severity of extrapyramidal side effects of antipsychotics was statistically significantly higher than in the carriers of the wild-type genotype: 13.27±5.10 versus 9.84±6.03 SAS scores, respectively (t=-2.40; p=0.020). In addition, the carriage of the wild allele A of SNP in the MTRR 66A>G gene (F=3.83; p=0.0283; pcorr.=0.043) is associated with the severity of extrapyramidal symptoms. There was a direct moderate correlation of the number of risk alleles at two loci with the total SAS score (r=0.51; p=0.00017).Conclusion. The polymorphic allele of MTHFR 677T and the wild allele of MTRR 66A can be regarded as risk alleles for the development of extrapyramidal side effects of antipsychotics.

Langerhans cell histiocytosis (LCH) is a rare disease with hitherto unknown etiology and pathogenesis. It is extremely rare for clinicians to encounter histiocytic lesions of the central nervous system (CNS); the proportion of cases of which is only 1–4% of all polysystemic and multifocal bone lesions. The paper describes a clinical case of fixation amnesia in a female patient with focal brain lesions in LCH. It depicts the most characteristic clinical features and presents an algorithm for the diagnosis of histiocytic brain lesion. The results of the experimental psychological examination of the patient are considered in detail and the clinical presentations of fixation amnesia are described. There are neuroimaging data showing the lesions in the hypothalamic-pituitary region and temporal bone, which involve the auditory structures. The clinical findings have led to the conclusion that both the clinical and neuroimaging patterns of histiocytic lesions in the CNS are non-specific, which complicates the diagnostic search in LCH. For correct diagnosis and timely treatment, it is necessary to perform a biopsy of the pathological focus, followed by histological and immunohistochemical examination of the material.

The search for new approaches to the mental disordersclassification is one of the priority tasks in modern psychiatry. Current approaches evaluate mental disorders in isolation, ignoring the fact that they are a multisystem pathology that affects not only mental functions, but also a wide range of somatic manifestations. However, there is more and more reason to consider mental disorders as multisystem diseases. This approach is of interest not only for explaining the high comorbidity of somatic and mental disorders, but also in studying the pathophysiological mechanisms that determine the risks and course of multisystem diseases. This strategy can be the basis for the fundamentally new approaches to the systematics of mental disorders with both theoretical and practical significance. To integratesuch an approach, it is necessary to determine the “starting point”, which may be the evaluation of mental disorders andinherited metabolic disorders interaction.

One of the many negative consequences of the COVID-19 pandemic is the “secondary epidemic” of negative psychological effectsThe aim of the study was to identify socio-psychological factors associated with adaptive behavior in the population.Materials and methods: an on-line survey of 1957 Russian-speaking respondents over 18 years old was performed from 30.03.2020 to 05.04.2020. The level of anxiety distress was verified with the psychological stress scale (PSM-25). Dispersion analyses were used (p

The biopsychosocial model, as well as a number of approaches and paradigms based on it (scientific, clinical, preventive, therapeutic), currently cause a lot of criticism up to the complete denial of its use in psychiatry possibilities. The aim of this paper is to propose a modern interpretation of the biopsychosocial model in psychiatry for the further studies of the mental disorders etiopathogenesis and for the research of new opportunities for their therapy and prevention. Progress in biological medicine and the emergence of new research technologies today open up new opportunities for the actual interpretation of the biopsychosocial model and its application for the modern biopsychosocial paradigm, which can be used both as a research strategy and for the relevant scientifically based methods of therapy and prevention. Thus, it is important to understand that the biopsychosocial model is not a competitor or antithesis of the biomedical model, but allows one to expand the biological boundaries beyond a simple description of the organs and systems functioning.

Controlling the epidemic of overweight and obesity is one of the major challenges to modern healthcare. One of the possible causes of overweight and obesity can be food addiction manifesting as overeating and other eating disturbances (ED).We conducted a cross-sectional study to test the association between addiction-related ANKK1/DRD2 gene Taq1A polymorphism (rs1800497) and ED in overweight patients. Overall, 527 outpatients (469 (89,0%) females, 58 (11,0%) males; mean ± SD: BMI — 35,8±7,3 kg/m2; age — 46,7±11,8 years) of European ancestry were included in the study. Eating Disorder Examination — Questionnaire (EDE-Q), Eating Attitudes Test (EAT-26) and Dutch Eating Behavior Questionnaire (DEBQ) were used to assess the ED. We also used Hospital Anxiety and Depression Scale (HADS), Hamilton Rating Scale for Depression (HRDS), Hamilton Anxiety Rating Scale (HARS) and Yale-Brown Obsessive-Compulsive Scale (YBOCS) to assess depressive, anxiety and obsessive-compulsive disturbances respectively. DNA was extracted from blood samples and polymorphism rs1800497 was detected by RT-PCR.According to the dominant genetic model, carriers of minor T allele (“CT+TT” group) in contrast to wild-type allele homozygous patients (“CC” group) were younger (p=0,075) and demonstrated higher scores of EDE-Q (p=0,085) and emotional eating subscale of DEBQ (p=0,063). Moreover, among them the proportion of patients with high ED risk was significantly increased vs. CC group: 1) EAT-26 score: 15,2% vs. 9,0%, OR=1,82 (CI95% (1,054-3,134), p=0,03; 2) EDE-Q score: 46,6% vs. 37,5%, OR=1,45 (CI95% (1,015-2,072), p=0,041. BMI was correlated with emotional eating subscale of DEBQ score in “CT+TT” group only (ρs =0,199, p=0,004). Correlation analysis showed weaker connections between ED and affective disturbances in “CT+TT” group.Our results show that carriers of the addiction-related T allele of ANKK1/DRD2 gene Taq1A polymorphism comprise the at-risk group for eating disturbances in overweight individuals. This may support the role of food addiction in overweight and obesity.

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.

The article presents an analytical review aimed at determining the effect of anhedonia on the course and therapeutic prognosis of depression. Currently, there is no specific pharmacological approach to the treatment of anhedonia in depression.It is clear all antidepressants that affect the symptoms of depression in general act to a certain extent on anhedonia. Modern views on the biological mechanisms involved in the formation of anhedonia are described, on the basis of which a search for drugs with anti-anhedonic activity is possible. Vortioxetine can be considered as an antidepressant with a specific anti-anhedonic effect.

Te article provides an overview of foreign and domestic literature on the development of complications associated with neuroleptic hyperprolactinaemia in patients with schizophrenia in the course of prolonged antiretroviral therapy with antipsychotics. Most researchers agree that long-term neuroleptic hyperprolactinemia signifcantly impairs the physical health of patients with mental disorders. Timely diagnosis and correction of this side effect of psychopharmacotherapy will signifcantly reduce the risk of complications and improve the social functioning of patients with schizophrenic disorders.

To predict the development of side effects and personalized selection of drug therapy, it seems relevant to study the association of individual genetic risk factors with undesirable side effects of antipsychotics in chronic patients with schizophrenia. Thereby the purpose of this study was to evaluate the association between the carriage of the T-allele of the single nucleotide genetic polymorphism MTHFR677C>T and the severity of the metabolic side effects of antipsychotics. As a result of the study a greater risk of developing components of the metabolic syndrome was revealed, as well as a significantly higher fasting blood glucose level in the group of carriers of the minor T-allele of polymorphism MTHFR677C>T.

The article presents modern data on the comorbidity of depression and obesity in terms of causation, general pathophysiological mechanisms of formation and development. It presents also the impact of one of the comorbid diseases on the success of the treatment another disease in the search for ways to improve the effectiveness of depression therapy. The expediency of isolation of specific depressive-metabolic endophenotype is shown. It allow to gain new knowledge about etiology and pathogenesis of depression, and to optimize therapy.

A plenty of studies show that the post- stroke depression is a difficult and complex problem, which bids defiance to the whole rehabilitation system. The solution of this objective definitely needs some specific diagnostic utilities and the most actual treatment methods. At the same time, there are some reasons, which do not allow us to reach an optimal rehabilitation result. In our paper we are reviewing both diagnostic problems of a post- stroke depression and some of the most promising diagnostic and treatment techniques, and hope that will help us solving an issue.

The article presents compelling evidence of the need to draw attention of physicians to the problem of neyroleptical hyperprolactinemia. The article provides information about different prolactogen activity of antipsychotics with the release of the safest drugs - aripiprazole and ziprasidone. Substantiates the necessity of correction prolactin levels during antipsychotic therapy. Presented the algorithms for the prevention and monitoring of neuroleptic hyperprolactinemia, as well as the basic principles of its correction, including with the use of a dopamine agonist Dostinex.

The article discusses various aspects of the main approaches to the issue of correction of neuroleptic hyperprolactinemia. Based on the generalized scientific and practical experience, algorithms for corrective therapy with dopamine agonists - bromocriptine and cabergoline (Dostinex) are given. The data on indications and contraindications to prescribing therapy with these drugs are substantiated, as well as features of their side effects.

The relationship between bipolar affective disorders (BAD) and epilepsy have an obvious comorbidity, similar theoretical bases of pathogenesis and treatment approaches. In both diseases, there is a high risk of suicide without treatment, the frequency of episodes of BAD increases, and the lucid intervals become shorter, the progression of the disease is similar to one as for epilepsy. Discusses general pathophysiological mechanisms of epilepsy and BAD and treatment of affective disorders of the bipolar spectrum in patients with epilepsy.

The article is devoted to the methods of overcoming therapeutic resistance in patients with schizophrenia, in particular, during the replacement of antipsychotic therapy. The issues of lack of common views on the problem of resistance are discussed, and in connection with this - the lack of algorithms for managing patients with these problems. Data on the parameters of resistance determination (residual productive symptoms, side effects of antipsychotics, etc.) are given. Data on pharmacokinetic interactions of antipsychotics and their endocrine side effects are presented. The advantage of using ziprasidone for overcoming therapeutic resistance in patients with schizophrenia is shown.

Cardio-metabolic risk factors and diabetes mellitus type 2 are highly prevalent in patients with schizophrenia. Decrease of metabolic risks associated with use of atypical antipsychotics is connected with the development of specialised programs. They can prevent and treat metabolic disorders. This article presents a comprehensive approach to the problem and proposes a solution to minimise the risk of metabolic disorders. The analysis dependence risk of formation of metabolic disorders with genetic factors, behavioral disorders, associated with schizophreniaand therapypresented in the article.

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.

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.

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.