Background: the immunological direction has always been a significant part of biological studies of schizophrenia and in different years has been based on the relevant fundamental ideas about the functions of the immune system and neuroimmune relationships. Objective: to conduct a brief historical analysis of immune hypotheses of schizophrenia, reflecting the vector of research of fundamental immunology, and also to present the results of our own research, confirming the key role of chronic inflammation in the pathogenesis of schizophrenia and the possibility of using immunological indicators for diagnosis and prognosis of the course of the disease. Materials and Method: using the keywords “schizophrenia”, “immune hypotheses of schizophrenia”, “neuroinflammation”, “neuroimmune relationships” we analyzed publications from PubMed/MEDLINE, RSCI databases and other sources of the last decades in comparison with the results of clinical and biological studies of schizophrenia at the Mental Health Research Centre (MHRC). Conclusion: based on the analysis of publications, it is shown that the development of scientfic ideas about the relationship between the immune system and schizophrenia has led to the understanding of the key role of chronic inflammation in the pathogenesis of this disease. Based on comparative studies of a number of immune markers related to cytokine system, acute phase proteins, proteolytic enzymes, etc., a laboratory test system “Neuroimmuno-test”, which includes complex determination of iflammatory and autoimmune markers in blood plasma, was created at the MHRC. It is shown that the level of immune system activation correlates with the features of psychopathological symptoms of patients. Identification of the immune profiles of patients is important to differentiate disease subtypes for the purpose of diagnosis and personalized therapy.

Background: Although there are international classifications of schizophrenia, the clinical approach to the systematization of schizophrenia developed by russian scientists has not lost its signifcance to date. The main role in the development of the schizophrenia of the national psychiatric school belongs to the famous Russian psychiatrist A.V. Snezhnevsky and his colleagues. The aim of review: to analyze the forms of the course of schizophrenia according to the concept of A.V. Snezhnevsky. Materials and methods: review of the main publications of A.V. Snezhnevsky and colleagues on the question of the doctrine of forms of schizophrenia course. Conclusion: The review summarizes the main research results of the national psychiatric school under the leadership of academician A.V. Snezhnevsky in the formation of the doctrine of schizophrenia.

Background: currently schizophrenia remains one of the most disabling diseases. Its clinical manifestations, course and outcome are extremely diverse. At the same time, there is no strict parallelism between the formal severity of illness and behavioral disorders. The aim of review is to analyze the available data on the relationship between clinical symptoms and cognitive deficits in patients with schizophrenia and behavioral disorders identified in them. Material and Method: the narrative review systematizes the data about influence of various clinical symptoms and their course on the behavior of patients with schizophrenia during the prodromal period, active course of the disease and during remission. Special attention is paid to the role of cognitive impairment, as well as the prevention of socially dangerous actions of mentally ill patients. An original typology of behavior of patients with schizophrenia in remission is considered. Conclusion: the analysis of the reviewed studies determines the possibilities of targeted psychosocial influence in order to form socially adaptive behavior in patients with schizophrenia.

Background: cognitive deficits in schizophrenia have long been believed to reflect the influence of genetic predisposition to the disease. Schizophrenia genome-wide association studies of the last decade have made it possible to test this hypothesis. The aim: to analyze studies on the relationship between cognitive impairment in schizophrenia patients and polygenic risk scores for schizophrenia (SZ-PRS). Additionally, the associations of PRS for intelligence with cognitive deficits in patients and the associations of SZ-PRS with cognitive functions in healthy people were considered. Material and methods: the literature search was carried out in the PubMed database using the following terms: (schizophr* OR schizoaffective* OR psychosis) AND (cogn* OR intelligence OR IQ) AND (GWAS OR polygenic). Results and discussion: from papers published between January 2015 and February 2024, 40 publications met the inclusion criteria. Their analysis indicate that in schizophrenia patients, in contrast to healthy people, the correlation of SZ-PRS with cognitive deficits and premorbid cognitive abilities is absent. Cognitive functions of patients are associated with PRS of intelligence, however, the bulk of the variance in cognitive deficits in schizophrenia, except for the group with intellectual disability, appears to be associated with non-genetic causes. It can be assumed that disease process factors play the most important role. Future studies should be aimed at establishing whether they are directly related to the pathophysiology of the disease, to the influence of concomitant exposures (treatment, hospitalization, etc.) or cognitive reserve, which will contribute to the correction of cognitive deficits.

Results: consumption of antipsychotics in hospital for the period 2015–2022 characterized by a decrease in the proportion of typical antipsychotics (TA) to 12.8% due to an increase in the proportion of atypical antipsychotics (AA) to 61.0% and long-acting antipsychotics (LA) to 26.2%. The administration of antipsychotics by hospital treatment units was relatively uniform. Clozapine (26.9%), zuclopenthixol (20.0%), haloperidol (10.3%), olanzapine (10.3%), risperidone (9.3%), quetiapine (8.2%), paliperidone (4.1%) accounted for 89.1% of all antipsychotics consumed. The total proportion of cariprazine, pericyazine, aripiprazole, ziprasidone, levomepromazine, chlorprothixene, chlorpromazine, tiapride and trifluoperazine, sertindole, lurasidone, sulpiride, flupenthixol and brexpiprazole was 10.9%. Among the medications prescribed to patients with schizophrenia, the leading ones were risperidone (36.2%), haloperidol (17.1%), olanzapine (15.6%), and clozapine (10.8%). The frequency of prescription of other drugs was less than 10.0%. The share of TA was 26.3%, AA — 73.7%. In the vast majority of cases (98.1%), patients received monotherapy. Conclusion: the data obtained on the structure of antipsychotic prescriptions indicate that our approaches correspond to the global trend of the predominant use of second-generation antipsychotics in the in-patient treatment of schizophrenia.

Background: the study of clinical remission in schizophrenia has a significant place at the current stage of development of psychiatric science. Prevention therapy and personalized prophylactic therapy is important to improve the quality of remission, stabilization of the endogenous process and prevention of exacerbation. The aim was to develop apathogenetically grounded method of treatment of episodic schizophrenia at the remission stage using complex assessment of clinical, psychometric and immunological parameters of patients, which allows to control the quality and stability of remission, as well as prediction of exacerbation of the endogenous process. Patients and methods: 91 patients (24 men and 67 women) aged from 18 to 70 years were examined. They were in remission after suffering attacks of an endogenous disease with episodic course (the duration of remissions ranged from 6 months to 12 years). Clinical-psychopathological, psychometric, immunological, clinical and followup, and statistical methods were used. Results: determination of inflammatory and autoimmune markers of blood plasma in the dynamics of the disease and their comparison with the severity of psychopathological symptomatology of patients with schizophrenia, made it possible to form 2 groups of patients with differently directed correlations between the change in clinical state (according to the PANSS scale) and the level of activation of the immune system, assessed in the aggregate immune markers determined. For patients of group 1 (n = 58; 63.74%) the decrease of the intensity of psychopathological symptoms in remission is associated with a decrease in the level of immune system activation («positive» correlations). For the patients of group 2 (n = 33; 36.26%) the level of immune system activation in remission does not decrease and remains at the level of the acute stage of the disease (“negative” correlations). It is shown that the increase in the level of immune system activation in patients of group 1 is a prognostic immunological criterion of possible exacerbation of psychopathological symptoms in remission. Based on the determination of immunological blood parameters in remission, personalized treatment tactics have been developed for these patients, associated with the transition from maintenance doses of drugs to therapeutic ones or additional use of drugs of another group. In most cases, this tactic contributed to relatively favorable dynamics of the existing clinical remission without significant changes in the condition. For patients of group 2, the personalized therapy tactics involves continuation of longterm active therapy. Conclusions: complex assessment of clinical, psychometric and immunological parameters of patients with episodic schizophrenia, which allows to control the quality and stability of remission, can be used to control the quality and stability of remission, as well as to detect preclinical signs of exacerbation of the endogenous process.

Background: impaired impulse control is thought to be an important hallmark of schizophrenia, which is closely related to the dysfunction of many of the neurophysiological systems of the central nervous system characteristic of the disease. The presence of increased impulsivity requires special attention in view of the risks associated with it, both for the patients themselves and for society. Aim of the study: to assess the presence of signs of a significant level of impulsivity in self-reporting on the Barratt scale in patients with paranoid schizophrenia in a state of exacerbation and remission. Patients and Methods: the study included two groups of patients suffering from paranoid schizophrenia both in a state of sustained remission with residual psychotic symptoms and patients in a state of exacerbation. Control group: consisted of healthy subjects. To assess impulsivity, the Barratt scale, adapted to the Russian population, was used. Results: it turned out that in both groups of patients, increased impulsivity was detected in half of the cases (54% and 46%, respectively). In the control group, only 22% had such cases. There were no differences between the groups of patients. When analyzing the ratio of indicators on different subscales of the Barratt scale, no differences were found both between the groups and in comparison, with the control group. Conclusion: the results of the study suggest that impulsivity as an element of the clinical picture, which is found in the patient’s self-report, may be an informative sign that should be taken into account when forming a psychopharmacological treatment regimen and rehabilitation programs. The Barratt scale can be used in patients with schizophrenia in everyday practice.

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.

Background: studies allowing to explore the neurobiological characteristics of the long-term schizophrenic process are of high significance for both clinical practice and biological psychiatry. Objective: to examine morphometric brain characteristics in chronic schizophrenia patients with different types of functional outcomes. Patients and methods: morphometric MRI characteristics of the cerebral cortex and subcortical structures are analysed in 46 patients with schizophrenia with a long disease durations (20.5 ± 6.7 years), and in 35 mentally healthy subjects matched by sex and age. Results and discussion: the whole group of patients showed decreased gray matter thickness in some cerebral cortex regions. When outcome was assessed using clinical-psychopathologic, clinical-catamnestic, and clinical-epidemiologic methods, bilateral increases in pallidum and putamen volumes were found to be a presumptive marker of worse functional outcome and remission poor quality. At the same time, when outcome was assessed on the basis of the current psychometric measures of social functioning and clinical symptomatology, patients with an unfavorable outcome were characterized by decreased gray matter thickness in the two cingulate cortex regions compared to both healthy controls and patients with a good outcome. However, the absence of correlations with clinical scales and functioning doesn’t allow a conclusion on the specificity of this decrease as a marker of outcome. Conclusion: the results may only presume beforehand the existence of different neuroanatomical subtypes (biotypes) associated with different functional outcomes in patients with chronic schizophrenia.

Background: endogenous psychoses complicated with different addictions have special psychopathological structure including delirious episodes, true hallucinations combined with typical positive symptoms of schizophrenia. These cases are difficult for treatment due to non-compliance of patients and their bad tolerance to drugs. The aim was to study the most effective psychopharmacological treatment using cariprazine for acute psychotic states in paranoid schizophrenia combined with chemical addictions. Patients and Methods: the study was conducted at psychiatric hospitals of Tomsk region, St. Petersburg, Nizhnevartovsk and Noyabrsk from 2018 to 2024. 208 men aged 18 to 45 years suffering from paranoid schizophrenia and dependent on psychoactive substances were examined. The main group made up 104 in-patients, who took cariprazine alone or in combination with haloperidol or chlorpromazine. The control group included 104 in-patients treated with other antipsychotics (aripiprazole, risperidone, olanzapine). Research methods: clinical and psychopathological, psychometric (PANSS, SANS, CGI, GAF), statistical (Python 3.11.0; R version 3.2.4; SPSS Statistics Base 22.0). Results: It was revealed that when comparing the control group with the main group, similar indicators were observed on the CGI and GAF scales on the 2nd week of the study, and on the 4th week of the study, compared with the control group, an improvement in indicators on the PANSS, SANS, CGI, GAF scales was observed. Conclusions: Cariprazine, compared with other atypical antipsychotics (risperidone, olanzapine, aripiprazole), showed a distinct antipsychotic effect in the treatment of acute psychotic states in patients with schizophrenia dependent on psychoactive substances. By the end of the 2nd week after hospitalization, when treating with cariprazine at an average dose of 3 to 6 mg/day in combination with typical neuroleptics (haloperidol, chlorpromazine) or a tranquilizer, the most pronounced antipsychotic effect is achieved. Subsequent isolated use of cariprazine at a therapeutic dose of 3–4.5 mg/day has an effect similar to that of leading atypical antipsychotics by the end of the 4th week of treatment. Unlike other atypical antipsychotics, cariprazine was more effective in the treatment of negative symptoms of schizophrenia, which made it possible to achieve an improvement in overall functioning, increase the duration of remission, and reduce the risk of rehospitalization and the development of hospitalism.