For citation: Fedorenko O.Yu., Ivanova S.A., Kornetova E.G. The role of gene polymorphism of the dopamine and glutamate systems in the clinical heterogeneity of schizophrenia and the development of antipsychotic-induced side effects. Siberian Herald of Psychiatry and Addiction Psychiatry. 2023; 1 (118): 5-13. https://doi.org/10.26617/1810-3111-2023-1(118)-5-13

The role of gene polymorphism of the dopamine and glutamate systems in the clinical heterogeneity of schizophrenia and the development of antipsychotic-induced side effects

Fedorenko O.Yu., Ivanova S.A., Kornetova E.G.

Mental Health Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences

Aleutskaya Street 4, 634014, Tomsk, Russian Federation

ABSTRACT

Objective: to search for genetic markers of the risk of development and adverse course of schizophrenia, as well as side effects of antipsychotic therapy to improve early diagnosis and personalized approaches to the treatment of this group of patients. Materials and Methods. A comprehensive clinical and biological examination was performed on the basis of Mental Health Research Institute of Tomsk National Research Medical Center, Tomsk Regional Clinical Psychiatric Hospital, and Kemerovo Regional Psychiatric Hospital. Status of patients (n=850) who underwent inpatient treatment in 2012-2022, at the time of the examination, met the diagnostic criteria for schizophrenia (F20) according to ICD-10. Psychopathological symptoms were assessed using the Positive and Negative Syndromes Scale (PANSS) and a modified version of the standardized description card for a patient with schizophrenia. The severity of adverse movement disorders during pharmacotherapy was assessed using the AIMS scale. The concentration of prolactin in the blood serum was determined by enzyme immunoassay. Discussion. The article presents the results of our own research in the field of genetics of clinical heterogeneity of schizophrenia and pharmacogenetics of antipsychotic-induced side effects in the paradigm of dysregulation of the dopamine and glutamate neurotransmitter systems. Associations of polymorphic variants of the genes of the dopamine and glutamate systems with unfavorable clinical phenotypes of schizophrenia, namely, with an early age of onset of the disease, a continuous type of course and leading negative symptoms, as well as with concomitant behavioral patterns (alcohol abuse and tobacco dependence), were revealed. Associations of polymorphic variants of genes of dopamine and glutamate systems with the risk of developing tardive dyskinesia, hyperprolactinemia and metabolic syndrome in patients with schizophrenia receiving long-term antipsychotic therapy are shown. The obtained fundamental data can serve as a basis for the development of new medical technologies.

Keywords:schizophrenia, genetics, pharmacogenetics, dopamine system, glutamate system.

Received December28.2022

Accepted February 24.2023

Fedorenko Olga Yu., D.Sc. (Medicine), lead researcher of the Laboratory of Molecular Genetics and Biochemistry, Mental Health Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk, Russian Federation. SPIN-code RSCI 5966-7492. ResearcherID E-3538-2015. Scopus Author ID 6603665833. ORCID iD 0000-0002-9565-6314.

Ivanova Svetlana A., D.Sc. (Medicine), Deputy Director for Research, Mental Health Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk, Russian Federation. ResearcherID С-5333-2012. Scopus Author ID 36113599800. ORCID iD 0000-0001-7078-323X. This email address is being protected from spambots. You need JavaScript enabled to view it.

Kornetova Elena G., D.Sc. (Medicine), headof the Endogenous Disorders Department, Mental Health Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk, Russian Federation. SPIN-code RSCI 6490-8758. ORCID iD 0000-0002-5179-9727. Sсоpus Author ID 35285972300. ResearcherID R-6811-2016. This email address is being protected from spambots. You need JavaScript enabled to view it.

Fedorenko Olga Yu., This email address is being protected from spambots. You need JavaScript enabled to view it.

For citation: Shushpanova T.V., Solonsky A.V., Shumilova S.N., Bokhan N.A. Formation of neuronal elements of the neuroimmune system of the human embryonic brain under the prenatal influence of alcohol. Siberian Herald of Psychiatry and Addiction Psychiatry. 2023; 1 (118): 14-22. https://doi.org/10.26617/1810-3111-2023-1(118)-14-22

Formation of neuronal elements of the neuroimmune system of the human embryonic brain under the prenatal influence of alcohol

Shushpanova T.V.¹, Solonsky A.V.^{1, 2}, Shumilova S.N.^{1, 2}, Bokhan N.A.^{1, 2}

¹ Mental Health Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences

Aleutskaya Street 4, 634014, Tomsk, Russian Federation

² Federal State Budgetary Educational Institution of Higher Education “Siberian State Medical University”

Moskovsky Trakt 20, 634050, Tomsk, Russian Federation

ABSTRACT

Introduction. Prenatal alcohol exposure affects the developing fetus, causes fetal alcohol spectrum disorders (FASD), and is a common human central nervous system developmental problem, but such studies are extremely rare, although significant. Alcohol activates innate immune signaling pathways in the brain. Neuroimmune molecules expressed and secreted by brain glial cells (microglia, oligodendroglia) alter neuronal function and further stimulate the development of alcohol behavior. Various signaling pathways and brain cells are involved in the transmission of neuroimmune signals. New understanding of the molecular mechanisms underlying FASD has led to the identification of new therapeutic targets associated with the neuroimmune system. Objective: to study neuronal elements: morphometric parameters of glioblasts, synaptic structures, and properties of synaptosomal GABA-benzodiazepine receptors of the neuroimmune system in human brain embryogenesis under prenatal alcohol exposure. Material and Methods. The sample of subjects included women of reproductive age (from 25 years to 41 years), the dividing of whom took place according to two parameters: 1) the absence of somatic or mental pathology and the absence of alcohol consumption before conception (in a period of 1 month) and during time of pregnancy; 2) diagnosed alcoholism stage I-II lasting 3-13 years. The collection of abortive material from human embryonic brain (HB) tissue was carried out during operations for artificial termination of pregnancy. Using an Ultracut-E ultratome (Reichert, Austria), semi-thin sections (0.5-1 µm) were obtained from these samples, which were stained with toluidine blue (Niessl dye) according to the standard method. The study of brain tissue samples was performed using an Axio Scope A1 light microscope (Carl Zeiss, Germany). For the subsequent photography, a Canon G10 digital camera was used. Parameters of GABA-benzodiazepine receptors were studied using radioreceptor analysis of [3H]-flunitrazepam (Amersham) on synaptosomal membranes of brain samples. Radioactive analysis of the amount of bound ligand was performed in a Rack-beta (LKB) scintillation beta counter. Results. Changes in glioblasts in the brain tissue of human embryos and fetuses in the conditions of chronic prenatal alcoholization and depending on the increase in the duration of pregnancy were revealed. A statistically significant increase in the average number of glioblasts was found as a result of a compensatory reaction due to a decrease in the size of glioblasts (p<0.01) in the main group of women with alcohol dependence compared to the control group of apparently healthy women. Ethanol exposure caused a decrease in the affinity of GABA-benzodiazepine receptors, that affected neuronal plasticity associated with the development and differentiation of progenitor cells (glioblasts and neuroblasts) during human brain embryogenesis and led to suppression of GABAergic function in the brain. Conclusion. Alcohol affects the neuronal regulation of innate immunity in brain cells by altering gene expression and molecular pathways that regulate neuroinflammation. The dynamics of changes in glial elements and receptor activity in the nervous tissue of human embryos and fetuses in the conditions of prenatal alcohol exposure indicates a more pronounced effect of alcohol at the earliest stages of human embryo development. Activation of glial cells during the period of toxic effects of alcohol is a necessary protective function of the brain.

Keywords:alcohol, GABA-benzodiazepine receptor, glia, brain, human, embryo.

Received December17.2022

Accepted February24.2023

Shushpanova Tamara V., Cand.Sc. (Medicine), lead researcher, Laboratory of Clinical Psychoneuroimmunology and Neurobiology, Mental Health Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk, Russian Federation. ResearcherID J-2817-2017. Author ID Scopus 6506299310. ORCID iD 0000- 0002-9455-0358. SPIN-code 9455-0358. Author ID 974543.

Solonsky Anatoly V., D.Sc. (Medicine), Prof., lead researcher, Laboratory of Clinical Psychoneuroimmunology and Neurobiology, Mental Health Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk, Russian Federation; Professor of the Department of Histology, Embryology and Cytology, Federal State Budgetary Educational Institution of Higher Education “Siberian State Medical University”, Tomsk, Russian Federation. SPIN-code 6687-9620. ResearcherID O-3610-2016. Author ID Scopus 6603017683. ORCID iD 0000-0002-1843-5833. This email address is being protected from spambots. You need JavaScript enabled to view it.

Shumilova Sofia N., junior researcher, Laboratory of Clinical Psychoneuroimmunology and Neurobiology, Mental Health Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk, Russian Federation; graduate student of the Department of Histology, Embryology and Cytology, Federal State Budgetary Educational Institution of Higher Education “Siberian State Medical University”, Tomsk, Russian Federation. This email address is being protected from spambots. You need JavaScript enabled to view it.

Bokhan Nikolay A., academician of RAS, D.Sc. (Medicine), Professor, Honored Scientist of the Russian Federation, Head of Addictive States Department, director of Mental Health Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences; Head of the Department of Psychiatry, Addiction Psychiatry and Psychotherapy, Siberian State Medical University, Tomsk, Russian Federation. Author ID Sсоpus 6506895310. ORCID iD 0000-0002-1052-855X. ResearcherID P-1720-2014. Author ID RSCI 152392. SPIN-code RSCI 2419-1263.

*Shushpanova Tamara V., This email address is being protected from spambots. You need JavaScript enabled to view it.; This email address is being protected from spambots. You need JavaScript enabled to view it.

For citation: Boksha I.S., Savushkina O.K., Omelchenko M.A., Prokhorova T.A., Tereshkina E.B., Vorobyeva E.A., Burbaeva G.Sh. Clustering of patients with clinical risk of schizophrenia by platelet biochemical parameters to predict psychopharmacotherapy efficacy. Siberian Herald of Psychiatry and Addiction Psychiatry. 2023; 1 (118): 23-31. https://doi.org/10.26617/1810-3111-2023-1(118)-23-31

Clustering of patients with clinical risk of schizophrenia by platelet biochemical parameters to predict psychopharmacotherapy efficacy

Federal State Budgetary Scientific Institution “Mental Health Research Centre”

Kashirskoe Highway 34, 115522, Moscow, Russian Federation

ABSTRACT

A clinical-psychopathological and clinical-biochemical study was carried out in the Laboratory of Neurochemistry and the Department of Juvenile Psychiatry of the Mental Health Research Centre. Objective: to select platelet biochemical parameters for individual prediction ofpsychopharmacotherapy efficacy in patients with depression at high risk of schizophrenia. Material and Methods. The main group (n=54) included males aged 16-25 years, hospitalized with the first depressive episode (F32.1, F32.2, F32.38, F32.8 according to ICD-10) in the structure of which attenuated symptoms of schizophrenia were determined. The severity of psychopathological symptoms was assessed using the Hamilton Scale (HDRS-21) and the scale of prodromal symptoms (SOPS). The control group consisted of 25 healthy males aged 19-25 years. Biochemical signs ‒the activities of four platelet enzymes: cytochrome c-oxidase (COX), glutamate dehydrogenase (GDH), glutathione reductase (GR), and glutathione-S-transferase (GST) were determined in apparently healthy control group and in patients of the main group before and after treatment. Clustering the patients of the main group according to 4 normalized baseline (before the treatment) biochemical signs was performed using the kappa-means clustering algorithm with the number of clusters equal to 3. Results. Three clusters (K1, K2, K3) were obtained with 19, 18 and 17 patients, respectively. GDH and GR in the clusters differed significantly before and after the treatment, and GST ‒only before the treatment. The baseline signs in the clusters were significantly lower than the corresponding values in the control group (except for COX in all clusters, and GDH in K3). After the treatment course, various but significant changes in the signs’ values were observed in all clusters. The search for links of baseline biochemical signs with scores by psychometric scales after the treatment, as well as with changes in the scores as a result of the treatment, revealed significant correlations that differed in different clusters. Conclusion. Determination of the baseline biochemical signs and clustering of patients according to the selected signs can be validated to stratify patients of a heterogeneous group with a clinical risk of schizophrenia with the aim to predict treatment efficacy in the selected subgroups individually.

Keywords:attenuated symptoms of schizophrenia, high risk for psychosis, cluster analysis, platelets, cytochrome c-oxidase, glutamate dehydrogenase, glutathione S-transferase, glutathione reductase.

Received January05.2023

Accepted February24.2023

Boksha Irina S., D.Sc. (Biology), chief researcher, Laboratory of Neurochemistry. Federal State Budgetary Scientific Institution “Mental Health Research Centre”. Moscow, Russian Federation. SPIN-code 4098-4837. ResearcherID B-6644-2009. Scopus Author ID 6602547274. ORCID iD 0000-0003-1369-8658.

Savushkina Olga K., Cand.Sc.(Biology), lead researcher, Laboratory of Neurochemistry. Federal State Budgetary Scientific Institution “Mental Health Research Centre”. Moscow, Russian Federation. SPIN-code 6558-9906. ResearcherID J-7330-2016. Scopus Author ID 6507180392. ORCID iD 0000-0002-5996-6606.

Omelchenko Maria A., D.Sc. (Medicine), llead researcher, Department of Juvenile Psychiatry. Federal State Budgetary Scientific Institution “Mental Health Research Centre”. Moscow, Russian Federation. SPIN-code 1643-9032. ResearcherID K-6508-2016. Scopus Author iD 35773602800. ORCID iD 0000-0001-8343-168X. E-mail This email address is being protected from spambots. You need JavaScript enabled to view it.

Prokhorova Tatyana A., researcher, Laboratory of Neurochemistry. Federal State Budgetary Scientific Institution “Mental Health Research Centre”. Moscow, Russian Federation. SPIN-code 7048-6289. ResearcherID S-2751-2016. Scopus Author ID 7004823848. ORCID iD 0000-0002-3574-2165. E-mail This email address is being protected from spambots. You need JavaScript enabled to view it.

Tereshkina Elena B., Cand.Sc. (Biology), senior researcher, Laboratory of Neurochemistry. Federal State Budgetary Scientific Institution “Mental Health Research Centre”. Moscow, Russian Federation. SPIN-code 6360-7072. ResearcherID S-2862-2016. Scopus Author ID 6602769146. ORCID iD 0000-0002-4784-8995. E-mail This email address is being protected from spambots. You need JavaScript enabled to view it.

Vorobyeva Elena A., Cand.Sc.(Biology), researcher, Laboratory of Neurochemistry. Federal State Budgetary Scientific Institution “Mental Health Research Center”. Moscow, Russian Federation. SPIN-code 4929-5034. ResearcherID J-8967-2018. Scopus Author ID 36807834300. ORCID iD 0000-0002-5766-0910. E-mail This email address is being protected from spambots. You need JavaScript enabled to view it.

Burbaeva Gulnur Sh., D.Sc. (Biology),Professor, Head of the Laboratory of Neurochemistry. Federal State Budgetary Scientific Institution “Mental Health Research Centre”. Moscow, Russian Federation. SPIN-code 9568-3420. ResearcherID S-2800-2016. Scopus Author ID 7003830468. ORCID iD 0000-0001-7744-533X. E-mail This email address is being protected from spambots. You need JavaScript enabled to view it.

Boksha Irina S., This email address is being protected from spambots. You need JavaScript enabled to view it.
Savushkina Olga K., This email address is being protected from spambots. You need JavaScript enabled to view it.

For citation: Markova E.V., Serenko E.V. Cytokine-mediated mechanisms for the correction of aggressive behavior by in vitro modulated immunocompetent cells. Siberian Herald of Psychiatry and Addiction Psychiatry. 2023; 1 (118): 32-40. https://doi.org/10.26617/1810-3111-2023-1(118)-32-40

Cytokine-mediated mechanisms for the correction of aggressive behavior by in vitro modulated immunocompetent cells

Markova E.V., Serenko E.V.

Federal State Budgetary Scientific Institution “Scientific Research Institute of Fundamental and Clinical Immunology”

Yadrintsevskaya Street 14, 630099, Novosibirsk, Russian Federation

ABSTRACT

Violation of neuroimmune interactions is an important link in the pathogenesis of aggression, including the formation of aggressive behavior. Cytokines, being messengers of intersystem functional connections, play an essential role in this. Previously, we obtained priority data on the possibility of editing patterns of aggressive behavior by immunocompetent cells modulated ex vivo with chlorpromazine. Objective: to study the role of cytokines in editing the behavior of aggressive recipients by in vitro modulated syngeneic immunocompetent cells. It has been shown that the correction of aggressive behavior after transplantation of syngeneic splenocytes modulated in vitro by Aminazin is registered against the background of a change in the content of a number of cytokines in the brain structures pathogenetically significant for aggression towards a decrease in pro-inflammatory cytokines IL-1β, IL-2, IL-6, IFN-γ and an increase in the anti-inflammatory cytokine IL-4, which indicates a decrease in neuroinflammation. At the same time, aggressive recipients also showed modulation of cytokine production by peripheral immunocompetent cells, which manifested itself in a decrease in mitogen-stimulated production of IFN-γ, IL-2, IL-6, and IL-10 by splenocytes. Opposite changes in cytokine levels observed during the formation of aggressive behavior and its relief indicate cytokine-mediated editing the behavioral phenotype of aggressive recipients after transplantation of syngeneic immunocompetent cells pre-cultivated with Aminazin. Visualization of functionally active splenocytes pre-cultivated with chlorpromazine in the parenchyma of not only the spleen, but also the brain of aggressive recipients also suggests a direct effect of the injected immunocompetent cells on the CNS cells.

Keywords:aggression, immunocompetent cells, chlorpromazine, brain, spleen, cytokines.

Received January19.2023

Accepted February24.2023

Markova Evgeniya V., D.Sc. (Medicine), Head of the Laboratory of Neuroimmunology, chief researcher of Federal State Budgetary Scientific Institution “Scientific Research Institute of Fundamental and Clinical Immunology”, chief researcher, Laboratory of Molecular Pathology, Federal State Budgetary Educational Institution of Higher Education “Novosibirsk State University”, Novosibirsk, Russian Federation. Author ID Sсоpus 7102093446. Author ID RSCI 109914. SPIN-code RSCI 8439-7310. ORCID iD 0000-0002-9746-3751.

Serenko Evgeny V., junior researcher of the Laboratory of Neuroimmunology, Federal State Budgetary Scientific Institution “Scientific Research Institute of the Basic and Clinical Immunology”, Novosibirsk, Russian Federation.

Markova Evgeniya V., This email address is being protected from spambots. You need JavaScript enabled to view it.

For citation: Vaiman E.E., Tumova M.A., Guseinova Z.T., Khasanova A.K., Efremov I.S., Schneider N.A., Ivanov M.V., Nasyrova R.F. Influence of single nucleotide polymorphisms of the serotonergic system genes on the occurrence of therapeutic resistance manifestations in patients with schizophrenia. Siberian Herald of Psychiatry and Addiction Psychiatry. 2023; 1 (118): 41-49. https://doi.org/10.26617/1810-3111-2023-1(118)-41-49

Influence of single nucleotide polymorphisms of the serotonergic system genes on the occurrence of therapeutic resistance manifestations in patients with schizophrenia

Vaiman E.E.¹, Tumova M.A.¹, Guseinova Z.T.¹, Khasanova A.K.²,

Efremov I.S.^{1, 3}, Schneider N.A.¹, Ivanov M.V.¹, Nasyrova R.F.¹

¹ Federal State Budgetary Institution^“V.M. BekhterevNational Medical Research Center for Psychiatry and Neurology”

of the Ministry of Health of Russia

Bekhterev Street 3, 192019, St. Petersburg, Russian Federation

²Federal State Budgetary Educational Institution “Russian Medical Academy of Continuing Postgraduate Education”

of the Ministry of Health of Russia

Barrikadnaya Street 2/1,building 1, 125993, Moscow, Russian Federation

³Federal State Budgetary Educational Institution of Higher Education

“Bashkir State Medical University” of the Ministry of Health of Russia

Lenin Street 3, 450000, Ufa, Russian Federation

ABSTRACT

Introduction. In recent years, the problem of treatment-resistant schizophrenia has been actively studied, but the etiology of this condition is not fully clear. One of the concepts of the pathogenesis of schizophrenia is a genetic theory, in particular, studying the influence of the carriage of single nucleotide polymorphisms (SNPs) of the serotonergic system genes. Objective: to determine the association and frequency of carriage of the SNP gene HTR2A rs7997012 (g.64185T>G, g.64185T>C, g.64185T>A) and rs6313 (g.6230C>T, g.6230C>G) with risk of development of therapeutically resistant schizophrenia during antipsychotic therapy. Materials and Methods. A prospective study was performed based on the Department of Biological Therapy of Mentally Ill of Federal State Budgetary Institution^“V.M. BekhterevNational Medical Research Center for Psychiatry and Neurology” of the Ministry of Health of Russia.The study sample included 103 patients with paranoid schizophrenia (F20.0 according to ICD-10) aged 18-50 years, including 53 women and 50 men. All patients were examined using the Positive and Negative Syndrome Scale (PANSS) at two points: by day 1 and day 56 of the study. Also, all patients underwent genetic testing to determine the carriage of the HTR2A gene under study. Depending on the response to therapy, groups of responders and non-responders were identified. Results. According to the findings of the study, it was determined that the dependent variable is dichotomous, and the independent variables are characterized as categorical. The final model included one significant variable – carriage of the heterozygous genotype CT SNP rs6313 (g.6230C>T) of the HTR2A gene. Conclusion. Determination of the genetic predisposition of patients with schizophrenia reveals the mechanisms for the development of therapeutically resistant schizophrenia, and also provides an opportunity to select effective therapy.

Keywords:schizophrenia, therapeutic resistance, serotonin receptors, antipsychotics, genetic predisposition.

Received January09.2023

Accepted February24.2023

Vaiman Elena E., junior researcher, Institute of Personalized Psychiatry and Neurology, V.M. Bekhterev National Medical Research Center for Psychiatry and Neurology of the Ministry of Health of Russia, St. Petersburg, Russian Federation. ORCID iD 0000-0001-6836-9590. e-mail This email address is being protected from spambots. You need JavaScript enabled to view it.

Tumova Marianna A., junior researcher, the 1^st Department of Biological Therapy of the Mentally Ill, V.M. Bekhterev National Medical Research Center for Psychiatry and Neurology of the Ministry of Health of Russia, St. Petersburg, Russian Federation. ORCID iD 0000-0002-3418-8596. e-mail This email address is being protected from spambots. You need JavaScript enabled to view it.

Guseinova Zumrud T., junior researcher, the 1^st Department of Biological Therapy of the Mentally Ill, V.M. Bekhterev National Medical Research Center for Psychiatry and Neurology of the Ministry of Health of Russia, St. Petersburg, Russian Federation. ORCID iD 0000-0002-6737-5486. e-mail This email address is being protected from spambots. You need JavaScript enabled to view it.

Khasanova Aiperi K., psychiatrist, assistant of the Department of Psychiatry, Federal State Budgetary Educational Institution “Russian Medical Academy of Continuing Postgraduate Education” of the Ministry of Health of Russia, Moscow, Russian Federation. ORCID iD 0000-0001-5391-0786. e-mail This email address is being protected from spambots. You need JavaScript enabled to view it.

Efremov Ilya S., psychiatrist, assistant of the Department of Psychiatry, Narcology and Psychotherapy with Institute of Additional Professional Education courses, “Bashkir State Medical University” of the Ministry of Health of Russia, Ufa, Russian Federation; researcher of the Institute of Personalized Psychiatry and Neurology, Federal State Budgetary Institution “V.M. Bekhterev National Medical Research Center for Psychiatry and Neurology” of the Ministry of Health of Russia, St. Petersburg, Russian Federation. ORCID iD 0000-0002-9994-8656. e-mail This email address is being protected from spambots. You need JavaScript enabled to view it.

Schneider Natalya A., D.Sc. (Medicine), Professor, lead researcher, Institute of Personalized Psychiatry and Neurology, Federal State Budgetary Institution “V.M. Bekhterev National Medical Research Center for Psychiatry and Neurology” of the Ministry of Health of Russia, St. Petersburg, Russian Federation. ORCID iD 0000-0002-2840-837X. e-mail This email address is being protected from spambots. You need JavaScript enabled to view it.

Ivanov Mikhail V., D.Sc. (Medicine), Professor, Head of the 1^st Department of Biological Therapy of the Mentally Ill, Federal State Budgetary Institution “V.M. Bekhterev National Medical Research Center for Psychiatry and Neurology” of the Ministry of Health of Russia, St. Petersburg, Russian Federation. SPIN-code 4709-5794. Author ID 701575. ORCID iD 0000-0001-7829-2486.

Nasyrova Regina F., D.Sc. (Medicine), chief researcher, Head of the Institute of Personalized Psychiatry and Neurology, Federal State Budgetary Institution “V.M. Bekhterev National Medical Research Center for Psychiatry and Neurology” of the Ministry of Health of Russia, St. Petersburg, Russian Federation. ORCID iD 0000-0003-1874-9434. e-mail This email address is being protected from spambots. You need JavaScript enabled to view it.

Ivanov Mikhail V., This email address is being protected from spambots. You need JavaScript enabled to view it.

For citation: Zozulya S.A., Popov S.M., Otman I.N., Barkhatova A.N., Klyushnik T.P. Clinical and immunological features in hysterical disorders that form in the structure of endogenous diseases of affective and schizophrenic spectrum. Siberian Herald of Psychiatry and Addiction Psychiatry. 2023; 1 (118): 50-58. https://doi.org/10.26617/1810-3111-2023-1(118)-50-58

Clinical and immunological features in hysterical disorders hatform in the structure of endogenous diseases of affective andschizophrenic spectrum

Zozulya S.A., Popov S.M., Otman I.N., Barkhatova A.N., Klyushnik T.P.

Federal State Budgetary Scientific Institution “Mental Health Research Centre”

Kashirskoye Highway 34, 115522, Moscow, Russian Federation

ABSTRACT

The study was performed based on the Laboratory of Neuroimmunology and the Department for the Study of Endogenous Mental Disorders and Affective States of the Federal State Budgetary Institution “Mental Health Research Centre”. Objective: to study the clinical and biological relationships between immunological blood parameters and the characteristics of the mental state of patients with hysterical disorders associated with endogenous mental illnesses of affective and schizophrenic spectrum. Material and Methods: the study included 34 patients (24 women and 10 men) aged 18 to 53 years (mean age 30.3±10.6 years) with hysterical disorders that develop within the framework of endogenous mental disorders of affective and schizophrenic spectrum (diagnosis codes according to ICD-10: F20, F21, F25, F31, F32, F33). All patients were examined for the severity of the manifestation of psychopathological symptoms during hospitalization in the clinic. Psychometric examination of patients was performed using the Hamilton Scale (HDRS) and the Positive and Negative Syndromes Scale (PANSS). Immunological examination included the determination of the activity of inflammatory markers - leukocyte elastase (LE) and α1-proteinase inhibitor (α1-PI), as well as the level of autoantibodies to the S-100B protein and myelin basic protein (MBP). Based on the totality of indicators, the overall level of activation of the immune system was assessed. Statistical processing of the results was carried out in the IBM SPSS Statistics 26 software package. Results. Patients with hysterical disorders demonstrate not only high clinical, but also immune heterogeneity, from a moderate increase in only inflammatory markers with the development of conversion symptoms to a pronounced increase in the activity of both inflammatory and autoimmune markers in patients with combined dissociative-conversion symptoms. Along with an increase in inflammatory markers, more than half of the examined patients are characterized by the presence of an autoimmune component to neuroantigens. The level of activation of the immune system, determined by the combination of inflammatory markers and the level of antibodies, reflects the severity of the mental state of patients with hysterical symptoms associated with both affective diseases and schizophrenia spectrum disorders. Accession of an autoimmune component is associated with the most severe intractable conditions.

Keywords:hysterical disorders, conversions, dissociative disorders, somatoform disorders, endogenous mental disorders, depression, schizophrenia, inflammatory and autoimmune markers.

Received December28.2022

Accepted February24.2023

Zozulya Svetlana A., Cand.Sc. (Biology), lead researcher, Laboratory of Neuroimmunology, Federal State Budgetary Scientific Institution “Mental Health Research Centre”, Moscow, Russian Federation. Author ID Sсоpus 57189596252. ORCID iD 0000-0001-5390-6007. Author ID RSCI 355958. SPIN-code RSCI 2968-9538.

Popov Sergey M., junior researcher, Department for the Study of Endogenous Mental Disorders and Affective States, Federal State Budgetary Scientific Institution “Mental Health Research Centre”, Moscow, Russian Federation. ORCID iD 0000-0001-7529-008X. Author ID RSCI 59817044. SPIN-code RSCI 5981-7044. e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.

Otman Irina N., Cand.Sc. (Biology), researcher, Laboratory of Neuroimmunology, Federal State Budgetary Scientific Institution “Mental Health Research Centre”, Moscow, Russian Federation. Author ID Sсоpus 35773604100. ORCID iD 0000-0003-3745-8413. Author ID RSCI 669208. SPIN-code RSCI 5357-7920. e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.

Barkhatova Alexandra N., D.Sc. (Medicine), Professor, Head of the Department for the Study of Endogenous Mental Disorders and Affective States, Federal State Budgetary Scientific Institution “Mental Health Research Centre”, Moscow, Russian Federation. Author ID Sсоpus 23491525300. ORCID iD 0000-0003-3805-332X. Author ID RSCI 221553. e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.

Klyushnik Tatyana P., D.Sc. (Medicine), Professor, Head of Laboratory of Neuroimmunology, director of Federal State Budgetary Scientific Institution “Mental Health Research Centre”, Moscow, Russian Federation. Author ID Sсоpus 6603398307. ORCID iD 0000-0001-5148-3864. Author ID RSCI 114497. e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.

Zozulya Svetlana A., This email address is being protected from spambots. You need JavaScript enabled to view it.

For citation: Nikitina V.B., Vetlugina T.P., Lobacheva O.A., Prokopieva V.D., Lebedeva V.F. Biological markers of the prognosis of the formation, course and effectiveness of therapy for mental disorders and alcohol addiction. Siberian Herald of Psychiatry and Addiction Psychiatry. 2023; 1 (118): 59-70. https://doi.org/10.26617/1810-3111-2023-1(118)-59-70

Biological markers of the prognosis of the formation, course andeffectiveness of therapy for mental disorders and alcohol addiction

Nikitina V.B., Vetlugina T.P., Lobacheva O.A., Prokopieva V.D.,

Lebedeva V.F.

Mental Health Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences

Aleutskaya Street 4, 634014, Tomsk, Russian Federation

ABSTRACT

Psychiatry as a science is at the stage of understanding the biological markers of mental pathology. Over the past decades, a large number of genetic, neuroimaging and neurophysiological studies have been carried out to search for them. At present, a priority scientific direction of research on the establishment of peripheral laboratory biomarkers of mental disorders is developing rapidly. Compared to subjectively assessed clinical and psychopathological signs and syndromes, biomarkers are more valid and reliable indicators. Objective: to summarize the results of research by the staff of the Laboratory of Clinical Psychoneuroimmunology and Neurobiology on the search for biological markers and their role in the formation, course and effectiveness of the treatment of mental disorders and alcohol dependence. Material and Methods. A clinical-psychopathological, psychological and immunobiological examination of patients undergoing inpatient treatment at the clinic of Mental Health Research Institute of Tomsk National Research Medical Center was carried out. Diagnostic evaluation was carried out according to the main clinical criteria of ICD-10. The survey sample included patients with adjustment disorder (F43.2) ‒ n=50, panic disorder (F41.0) - n=40, schizophrenia (F20.00, F20.01, F20.02, F20.6) ‒ n=156, mental and behavioral disorders due to alcohol use (addiction syndrome ‒ F10.21 and withdrawal syndrome ‒ F10.30) ‒ n=54. The level of reactive and personal anxiety, the severity of psychopathological symptoms according to the PANSS scale, and the dynamics of mental state improvement according to the CGI scale were assessed. Laboratory research included phenotyping of immunocompetent cells by differentiation clusters by flow cytometry, hormone determination by ELISA. The obtained data were statistically processed using STATISTICA for Windows (version 12.0). Comparison of independent samples was performed using the Mann-Whitney U-test. Results. A method is proposed for predicting the risk of developing a panic disorder at an early stage of the disease ‒ at the stage of adjustment disorder ‒ by assessing the level of reactive and personal anxiety in patients with adjustment disorder, determining the concentration of cortisol and natural killer cells in the blood. A complex of clinical-psychopathological and peripheral biomarkers was revealed to predict the effectiveness of therapy in patients with schizophrenia. The levels of free thyroxine, carbonylated proteins, and TBA-reactive products can be used as biological markers for predicting the duration of remission after anti-alcohol therapy in order to identify a cohort of patients with unstable therapeutic remission. Conclusion. Informative biomarkers have been found to predict the formation of panic disorder at an early stage of the disease, the effectiveness of therapy in patients with schizophrenia, and the duration of remission after therapy in patients with unstable remission in alcohol dependence.

Keywords:biomarkers, immunity, cortisol, triiodothyronine, thyroxine, carbonylated proteins, TBA-reactive products, reactive and personal anxiety, adjustment disorder, panic disorder, schizophrenia, alcohol dependence, effectiveness of therapy, duration of remission.

Received December12.2022

Accepted February 24.2023

Nikitina Valentina B., D.Sc. (Medicine), Head of the Laboratory of Clinical Psychoneuroimmunology and Neurobiology, Mental Health Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk, Russian Federation. ResearcherID B-9926-2012. Author ID Sсоpus 55640240200. ORCID iD 0000-0002-1644-770X. AuthorID RSCI 154172. SPIN-code RSCI 3687-7727.

Vetlugina Tamara P., D.Sc. (Biology), Prof., lead researcher, Laboratory of Clinical Psychoneuroimmunology and Neurobiology, Head of the Department of Biological Psychiatry and Narcology, Mental Health Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk, Russian Federation. ResearcherID C-2144-2012. Author ID Sсоpus 6603120359. ORCID iD 0000-0003-2068-0931. AuthorID RSCI 137410. SPIN-code RSCI 4237-1873. This email address is being protected from spambots. You need JavaScript enabled to view it.

Lobacheva Olga A., D.Sc. (Biology), lead researcher, Laboratory of Clinical Psychoneuroimmunology and Neurobiology, Mental Health Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk, Russian Federation. ResearcherID C-2151-2012; J-1783-2017. Author ID Sсоpus 26421227200. ORCID iD 0000-0002-7477-6296. AuthorID RSCI 614395. SPIN-code RSCI 9442-6470. This email address is being protected from spambots. You need JavaScript enabled to view it.

Prokopieva Valentina D., D.Sc. (Biology), lead researcher, Laboratory of Clinical Psychoneuroimmunology and Neurobiology, Mental Health Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk, Russian Federation. ResearcherID J-1713-2017. Author ID Sсоpus 6601960775. ORCID iD 0000-0002-4811-984X. AuthorID RSCI 123653. SPIN-code RSCI 8927-5645. This email address is being protected from spambots. You need JavaScript enabled to view it.

Lebedeva Valentina F., D.Sc. (Medicine), chief physician of clinic of Mental Health Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk, Russian Federation. SPIN-code RSCI 3509-4798, AuthorID RSCI 560284, ORCID iD 0000-0001-9266-8291.

Nikitina Valentina B., This email address is being protected from spambots. You need JavaScript enabled to view it.

For citation: Yazykova A.B., Novoselova A.E., Tsarkov I.E., Zhilyaeva T.V. Identification of biomarkers of schizophrenia using mass spectrometry methods (literature review). Siberian Herald of Psychiatry and Addiction Psychiatry. 2023; 1 (118): 71-81. https://doi.org/10.26617/1810-3111-2023-1(118)-71-81

Identification of biomarkers of schizophrenia using mass spectrometry methods (literature review)

Yazykova A.B.¹, Novoselova A.E.¹, Tsarkov I.E.,¹, Zhilyaeva T.V.^{1, 2}

¹ Federal State Budgetary Educational Institution of Higher Education “Privolzhsky Research Medical University”

Minin and Pozharsky Square10/1, 603005, Nizhny Novgorod, Russian Federation

¹ Federal State Budgetary Institution^“V.M. BekhterevNational Medical Research Center for Psychiatry and Neurology”

of the Ministry of Health of Russia

Bekhterev Street 3, 192019, St. Petersburg, Russian Federation

ABSTRACT

Objective:to analyze the results of modern domestic and foreign studies of biological markers of schizophrenia using mass spectrometry methods, highlight the main promising areas of research in the field of metabolomics and proteomics in schizophrenia, discuss the principles of operation and modern capabilities of various modifications of mass spectrometers in the analysis of proteomic and metabolomic composition of biological fluids of patients with schizophrenia. As a result of the analysis of literature data with a generalization of the currently available results of original studies, systematic reviews and meta-analyses, information is presented on the main groups of biomarkers and the leading mechanisms of pathogenesis, which are currently most actively studied in schizophrenia by mass spectrometry, as well as on the limitations of metabolomics in the study of this disease.

Keywords:schizophrenia, biological markers, metabolomics, proteomics, mass spectrometry.

Received January16.2023

Accepted February24.2023

Yazykova Anna B., senior lecturer, Department of Biochemistry named after G.Ya. Gorodisskaya, Federal State Budgetary Educational Institution of Higher Education “Privolzhsky Research Medical University”, Nizhny Novgorod, Russian Federation. SPIN-code RSCI 5581-2668. ResearcherID HOF-1081-2023. Author ID Scopus 56641762100. ORCID iD 0000-0002-3582-7687. This email address is being protected from spambots. You need JavaScript enabled to view it.

Novoselova Anastasia E., student of the 5th year of the Faculty of Medicine, Federal State Budgetary Educational Institution of Higher Education “Privolzhsky Research Medical University”, Nizhny Novgorod, Russian Federation. SPIN-code RSCI 2524-6140. ResearcherID HOF-3394-2023. This email address is being protected from spambots. You need JavaScript enabled to view it.

Tsarkov Ivan E., student of the 5th year of the Faculty of Medicine, Federal State Budgetary Educational Institution of Higher Education “Privolzhsky Research Medical University”, Nizhny Novgorod, Russian Federation. ResearcherID HOF-3413-2023. This email address is being protected from spambots. You need JavaScript enabled to view it.

Zhilyaeva Tatyana V., associate professor, Department of Psychiatry, Federal State Budgetary Educational Institution of Higher Education “Privolzhsky Research Medical University”, Nizhny Novgorod, Russian Federation; lead researcher, Department of Translational Psychiatry, Federal State Budgetary Institution “V.M. Bekhterev National Medical Research Center for Psychiatry and Neurology” of the Ministry of Health of Russia, St. Petersburg, Russian Federation. SPIN-code RSCI 7477-9182. ResearcherID J-4345-2012. Author ID Scopus 57034201100. ORCID iD 0000-0001-6155-1007.

Zhilyaeva Tatyana V, This email address is being protected from spambots. You need JavaScript enabled to view it.

For citation: Golygina S.E., Tereshkov P.P., Sakharov A.V. Blood immune response checkpoints in patients with the first episode of paranoid schizophrenia before therapy (preliminary results).Siberian Herald of Psychiatry and Addiction Psychiatry.2023; 1 (118): 82-90. https://doi.org/10.26617/1810-3111-2023-1(118)-82-90

Blood immune response checkpoints in patients with the first episode of paranoid schizophrenia before therapy (preliminary results)

Golygina S.E., Tereshkov P.P., Sakharov A.V.

FederalState Budgetary Educational Institution of Higher Education “Chita State Medical Academy”

of the Ministry of Health of the Russian Federation

Gorky Street 39A, 672090, Chita, Russian Federation

ABSTRACT

Introduction. The role of immune response checkpoints involved in the processes of neuroinflammation is not well understood in schizophrenia, especially in patients with the first episode of the disease. Objective: to study the parameters of some immunological checkpoints in blood plasma in patients with the first episode of paranoid schizophrenia before the administration of therapy. Material and Methods. Based on the Regional Clinical Psychiatric Hospital named after V.Kh. Kandinsky, Chita, 18 patients with the diagnosis of paranoid schizophrenia, observation period less than a year (ICD-10 code F20.x9) were examined, the control group included 35 subjects. Determination of the content of 12 control points of the immune response in the blood serum was carried out by flow fluorometry. Blood sampling was carried out before the start of therapy. Results. In patients with the first episode of schizophrenic psychosis, there is an increase in blood levels relative to the control values of sCD25 (IL-2Ra) by 1.4 times, PD-1 and Galectin-9 ‒ by 1.2 times, LAG-3 ‒ by 1.1 times. PD-L2 was reduced by 1.3 times. Conclusion. The findings indicate the significance of neuroimmunopathological mechanisms in the onset of schizophrenia, the exact significance of which requires further study.

Keywords:neuroinflammation, schizophrenia, first psychotic episode, immune response checkpoints.

Received December09.2022

Accepted February24.2023

Golygina Svetlana E., Cand.Sc. (Medicine), associate professor of the Department of Psychiatry, Narcology and Medical Psychology. Federal State Budgetary Educational Institution of Higher Education “Chita State Medical Academy” of the Ministry of Health of the Russian Federation, Chita, Russian Federation. AuthorID RSCI 847556. AuthorID Scopus 57201322291. ResearcherID HDN-9381-2022.

Tereshkov Pavel P., Cand.Sc. (Medicine), Head of the Laboratory of Experimental and Clinical Biochemistry and Immunology, Research Institute of Molecular Medicine. Federal State Budgetary Educational Institution of Higher Education “Chita State Medical Academy” of the Ministry of Health of the Russian Federation, Chita, Russian Federation. AuthorID RSCI 520402. This email address is being protected from spambots. You need JavaScript enabled to view it.

Sakharov Anatoly V., D.Sc. (Medicine), associate professor, first vice-rector, Head of the Department of Psychiatry, Narcology and Medical Psychology. Federal State Budgetary Educational Institution of Higher Education “Chita State Medical Academy” of the Ministry of Health of the Russian Federation, chief freelance pediatric specialist-psychiatrist of the Ministry of Health of Russia in the Far Eastern Federal District Chita, Russian Federation. Author ID RSCI 556868. Author ID Scopus 57201327574. ResearcherID N-4261-2016.

Sakharov Anatoly V., This email address is being protected from spambots. You need JavaScript enabled to view it.
Golygina Svetlana E., This email address is being protected from spambots. You need JavaScript enabled to view it.

For citation: Davydova T.V., Vetrile L.A., Zakharova I.A. Antibodies to neurotransmitters ‒ possible biomarkers of Alzheimer's disease and depressive disorders. Siberian Herald of Psychiatry and Addiction Psychiatry. 2023; 1 (118): 91-95. https://doi.org/10.26617/1810-3111-2023-1(118)-91-95

Antibodies to neurotransmitters ‒possible biomarkers of Alzheimer's disease and depressive disorders

Davydova T.V., Vetrile L.A., Zakharova I.A.

Federal State Budgetary Scientific Institution “Research Institute of General Pathology and Pathophysiology”

Baltiyskaya Street8, 125315, Moscow, Russian Federation

ABSTRACT

Background.An important role in the development of technologies for personalized prevention, in particular the search for biomarkers of neuropsychiatric diseases, is played by the study of molecular neuroimmune mechanisms of their development. According to modern data, one of the leading links in the neurochemical mechanisms in their development are disorders of the neurotransmitter systems of the brain. At present, a close relationship has been revealed between the dysfunction of neurotransmitter systems and the induction of autoantibodies to them in various forms of CNS pathology. Objective: to analyze the content of antibodies to dopamine, serotonin and glutamate in the blood sera of patients with AD in comparison with the level of these antibodies in patients with depressive disorders. Materials and Methods. The study was performed on samples of 75 blood sera from women aged 65-85 years with a verified diagnosis of Alzheimer's disease, 32 blood sera from women aged 45-55 years with a verified diagnosis of depressive disorders, and 59 blood sera from apparently healthy women who underwent medical examination. Antibodies to the neurotransmitter’s dopamine, serotonin, and glutamate were determined by solid-phase ELISA. Conjugates of the neurotransmitter with bovine serum albumin (BSA) were used as test antigens. Conjugated antigens of dopamine and serotonin with BSA were synthesized using diazotized protein. Glutamate-BSA conjugate was synthesized using glutaraldehyde. The data obtained were statistically processed using the nonparametric Mann-Whitney test. Results. In the blood sera of patients with Alzheimer's disease, an increased content of autoantibodies to dopamine, serotonin, and glutamate was found compared to their content in control blood sera from apparently healthy women, as well as in blood sera from patients with depressive disorders. The combination of Alzheimer's disease with depressive disorders leads to an increase in the level of autoantibodies to dopamine, serotonin and glutamate in blood serum compared to their content in depressive disorders. Conclusion. The results obtained allow us to consider autoantibodies to dopamine, serotonin and glutamate as neuroimmune markers of Alzheimer's disease.

Keywords:Alzheimer's disease, depression, antibodies, dopamine, serotonin, glutamate.

Received December21.2022

Accepted February 24.2023

Davydova Tatyana V.,D.Sc. (Medicine), chief researcher, Laboratory of General and Perinatal Neuroimmunopathology, Federal State Budgetary Scientific Institution “Research Institute of General Pathology and Pathophysiology”, Moscow, Russian Federation. ORCID iD 0000-0002-3176-1035.

Vetrile Luchiya A.,Cand.Sc. (Medicine), lead researcher, Laboratory of General and Perinatal Neuroimmunopathology, Federal State Budgetary Scientific Institution “Research Institute of General Pathology and Pathophysiology”, Moscow, Russian Federation. ORCID iD 0000-0001-9783-4711.

Zakharova Irina A., Cand.Sc. (Biology), lead researcher, Laboratory of General and Perinatal Neuroimmunopathology, Federal State Budgetary Scientific Institution “Research Institute of General Pathology and Pathophysiology”, Moscow, Russian Federation.ORCID iD 0000-0002-5648-4214.

Davydova Tatyana V., This email address is being protected from spambots. You need JavaScript enabled to view it.

For citation: Smirnova K.V., Chizhova N.D., Amstislavskaya T.G. Effects of chronic emotional stress on the behavior of mice with q31l and l100p mutations in the Disc1 gene. Siberian Herald of Psychiatry and Addiction Psychiatry. 2023; 1 (118): 104-113. https://doi.org/10.26617/1810-3111-2023-1(118)-104-113

Effects of chronic emotional stress on the behavior of mice with q31l and l100p mutations in the Disc1 gene

Smirnova K.V.¹, Chizhova N.D.¹, Amstislavskaya T.G.^{1, 2}

¹Federal State Budgetary Scientific Institution “Research Institute of Neurosciences and Medicine”

Timakov Street 4, 630117, Novosibirsk, Russian Federation

² Federal State Autonomous Educational Institution of Higher Education “Novosibirsk National Research State University”

Pirogov Street 1, 630090, Novosibirsk, Russian Federation

ABSTRACT

Both genetic and environmental factors are often involved in the etiology of mental illness. Mutations in the Disc1 gene are in themselves predictors of the development of psychopathologies, while at the same time, there are no data on the effect of chronic stress on the emotionally conditioned (affective) behavior of an organism with mutations in the Disc1 gene. Objective: to study the features of the behavioral response of mice with mutations in the Disc1 gene after an unpredictable emotional and stressful impact of different duration. Materials and Methods. Testing was carried out on n three-four-month-old male mice of three genetic lines (WT and with a point mutation in the Disc1 gene, Q31L and L100P). To study the behavioral response of mice with mutations Disc1-Q31L-/- (Q31L) and Disc1-L100P-/- (L100P), characterized by depression-like and schizophrenia-like behavior, were subjected to chronic unpredictable mild stress (CUMS) of two and four, respectively. After exposure to stress, their anxiety, motor and exploratory activity, emotionality, depressive-like and obsessive-compulsive behavior, social motivation, and preference were assessed. It was found that two-week stress increased anxiety and depression-like behavior in Q31L mice, and four-week stress increased their motor activity, but had no effect on anxiety and depression-like status. In L100P mice, both two and four weeks of stress resulted in depression-like behavior. In addition, two-week stress increased emotionality and social interaction, while four-week stress decreased the mice's exploratory activity. Thus, the genetically determined depression-like state in Q31L mice increases as a result of stress exposure for two weeks, while mice with a genetically determined schizophrenia-like L100P phenotype form a depression-like status after chronic stress of different duration.

Keywords:DISC1 protein, chronic stress, depression, schizophrenia, psychopathology modeling, mice.

Received December26.2022

Accepted February 24.2023