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: the role of the sex factor in the differences between the manifestations of normality and pathology is not limited to the phenomenon of sexual dimorphism. It is known that the prevalence of certain diseases in males and females is different, in particular, there is a multiple increase in the incidence of dementia in females compared to males in Alzheimer’s disease (AD). Taking into account the role of neuroinflammation in the pathogenesis of neurodegenerative diseases, there is reason to assume gender differences in inflammation indicators at different stages of dementia in AD. The aim of the study was to conduct comparative analysis of indicators of the inflammatory system in the blood plasma of males and females at different stages of Alzheimer’s disease. Patients, control group and methods: a total of 210 patients with AD (101 males and 109 females) aged 49 to 94 years (average age 72.3 ± 8.2) with varying degrees of dementia severity, i.e. mild, moderate, severe, were examined. In peripheral blood plasma, the enzymatic activity of leukocyte elastase (LE) and the functional activity of α1-proteinase inhibitor (α1-PI) were determined by the spectrophotometric method, and the level of C-reactive protein (CRP) and IL-6 were determined by the enzyme-linked immunosorbent method (ELISA). The control group consisted of 52 healthy people, who did not differ from the patients in age and gender. Results and discussion: in the blood of patients with varying severity of dementia in AD, a statistically significant increase in α1-PI activity was observed compared to controls (p < 0.0001), regardless of gender. For all subgroups of patients with AD, the indicators of LE enzymatic activity were within the control range or beyond its lower limit. Low LE activity was observed in males compared to females both in the general group and in moderate dementia (p = 0.005105, p = 0.028672, respectively). In severe dementia, a significant decrease in LE activity compared to the controls did not depend on gender. Low LE activity in the blood of patients with AD, along with elevated levels of other inflammatory markers, may reflect a critical violation of the permeability of the blood-brain barrier and/or functional exhaustion of neutrophils due to a long-term inflammatory process. In males, compared with females, an increase in the level of the pro-inflammatory cytokine IL-6 was detected in the general group and in moderate dementia (p = 0.021238, p = 0.027894, respectively). A highly significant increase in CRP levels was only detected in males in subgroups with different severity of dementia. CRP levels in males were significantly higher than in females at the stage of moderate and severe dementia (p = 0.000906, p = 0.000049, respectively). Conclusion: distinctive features of inflammatory markers spectrum were identified, depending on gender and severity of dementia in AD. These results can be used to develop sex-specific preventive or therapeutic strategies for patients with mild cognitive impairment to determine risk and resistance to developing dementia.

Background: the dorsolateral prefrontal cortex (DLPFC) is one of the latest brain structures to mature during the ontogeny, and its structural and functional abnormalities play an important role in the pathogenesis of schizophrenia. As schizophrenia spectrum disorders usually start before the complete brain maturation and their earlier onset is coupled with worse prognosis, we suggested that earlier illness onset is related to more pronounced aberrations of the DLPFC. The aim of study was to analyze the associations of the onset age of schizophrenia spectrum disorders with structural and functional characteristics of the DLPFC that differentiated patients with schizophrenia spectrum disorders from healthy controls. Patients and methods: male patients with a diagnosis of schizophrenia spectrum disorders (n = 82) and healthy controls (n = 86) underwent structural MRI and functional resting-state fMRI. Cortical thickness and whole-brain functional connectivity of the DLPFC as well as local coherence and amplitude of low-frequency fluctuations of haemodynamic signal in the DLPFC were analyzed. Results: patients demonstrated a decreased gray matter thickness in the DLPFC bilaterally along with aberrant (predominantly decreased) functional connectivity of the DLPFC with other brain structures in each hemisphere. These measures were not associated with the age of illness onset. Conclusions: structural and functional abnormalities revealed in this study coincide with conventional view on the DLPFC as one of the key regions in schizophrenia spectrum disorders pathogenesis, however, these aberrations were not related to the age of psychosis onset. Possible interpretations of our results and limitations of the study are discussed in the article.

Background: despite a significant progress of psychopharmacology, treatment-resistant schizophrenia (TRS) remains a challenge for clinicians. The etiology and pathogenesis of TRS probably differ from schizophrenia susceptible to therapy, which underlies the non-respondence to most antipsychotics.Objective: to establish morphometric gray matter brain structural features in TRS as well as to analyze the association of these parameters with the clinical characteristics of patients.Patients and methods: 21 right-handed male patients diagnosed with paranoid schizophrenia and meeting criteria for treatment resistance and 21 matched healthy controls underwent MRI and clinical examination. T1-weighted images were processed via FreeSurfer 7.1.1. For each subject average values for the cortex thickness and area, volumes of subcortical structures, brain stem structures, and separately volumes of the amygdala nuclei and hippocampal subregions were obtained. Intergroup comparisons and correlations with clinical scales (PANSS, CDSS) and antipsychotic dosage in chlorpromazine equivalent were calculated. Results: TRS patients showed decreased gray matter thickness in frontal, temporal, parietal, occipital, cingulate and insular regions, volumes of the amygdala, hippocampus and nucleus accumbens, as well as a number of amygdala nuclei and hippocampal subregions bilaterally. The volume of the right globus pallidus, on the contrary, was increased.Conclusion: the widespread gray matter thinning in TRS confirmed the other researchs, which described resistance as a more severe form of schizophrenia that affects brain structures worse. The increase of globus pallidus volume is a surprising result, which is not yet clearly explained.

Background: brain structural peculiarities in different mental disorders are neurobiological indicators that are extremely important both for understanding of the diseases’ pathogenesis and for identifying potentially valid prognostic markers. The aim of this pilot study was to identify the range of brain morphometric parameters in the group of patients with schizotypal disorders with catatonia syndrome. Patients and methods: 33 patients with schizotypal disorder and 33 age-matched mentally healthy subjects underwent high-resolution structural MRI on a 3T Philips Ingenia scanner. Results: there were found widely distributed intergroup differences in form of the smaller gray matter thickness. In this spectrum, a morphometric abnormality of the precentral gyrus, an area of the primary motor cortex localization, previously not noted in the literature on schizotypal disorder, drew special attention. In addition, smaller volume of the nuclei accumbens (included in the processes of choosing actions) was found. Conclusions: this pilot study allowed to reveal some brain elements of the mosaic presumably associated with the manifestation of catatonia syndrome in schizotypal disorder.

Background: tinnitus is the perception of acoustic, phantom sounds in the ear and/or head in the absence of an external source. The prevalence of tinnitus is 5–15 % in the population. The occurrence of subjective noise may have a number of possible causes, but the causal relationship between psychiatric disorders and tinnitus remains insufficiently proven, according to previous studies. The aim was to study an acoustic phenomenon of the “ear/head noise” type, comparable with tinnitus symptomatology, in the absence of otorhinolaryngological, neurological, somatic pathologies. Patients and methods: the sample consisted of 12 patients (11 men, 1 woman, mean age 38 ± 8.5 years) who underwent complex psychopathological, pathopsychological, psychometric, otorhinolaryngological, neurological, and instrumental examinations, statistical. The patients met the diagnostic criteria of subjective tinnitus according to ICD-10 classification (code H93.1). Results: the psychopathological qualification of tinnitus in our observations corresponds to psychosensory disorders of the synesthesia type. In the most cases, the ear noise occurred against the background of already long-standing neurotic or overvalued hypochondria. Depending on clinical picture of ear noise, and features of the course of hypochondriacal disorder, the acoustic phenomenon of the “ear / head noises” type was revealed within four nosologies: hypochondriacal schizophrenia, schizotypal disorder, cluster B personality disorder with the phenomenon of hypochondriacal diathesis, paranoid personality disorder with the phenomenon of overvalued hypochondria. Conclusion: the results of the present study, in spite of a limited number of observations, allow us (as a working hypothesis) to propose the following statement: the acoustic phenomenon of the “ear / head noise” type can manifest in psychiatric disorders (psychopathological phenomena of the hypochondriacal circle) duplicating the symptoms of tinnitus at clinical level which, are formed within otolaryngological, neurologicl and somatic pathology. Taking into account these clinical data, hypochondriacal formations appearing in the considered casuistic of the present study, having no base of otorhinolaryngology-related pathology, or internal organ pathology, can be qualified in accordance with the criteria presented in publication A. B. Smulevich et al. (2023) as a part of somatic paranoia. Further comprehensive study of this phenomenon is necessary for more accurate verification of the clinical criteria for differential diagnosis, increasing the efficiency of identifying the pathology under discussion, and determining rational methods of complex treatment, including psychopharmacotherapy and psychotherapeutic modalities.

Background: the results of studying the role of neuroinflammation in the pathogenesis of chronic mental disorders guide the scientific search for ways to apply conceptual notions to clinical practice. The aim: to present an overview of clinical and biological studies conducted jointly by clinicians and employees of the Laboratory of Neuroimmunology of the FSBSI “Mental Health Research Centre” and aimed at determination of the significance of immune biomarkers for the diagnosis, prognosis and treatment of various types of mental pathology. Method: the methodological equipment of this study is provided by the use of the original “Neuro-immuno-test” medical technology, developed at the FSBSI “Mental Health Researh Centre”, in comparison with the clinical data. Results and discussion: summarizing the results of many years of research showed that various inflammatory markers, determined in the blood of patients, can be used to assess the level of inflammation in the brain. Studies in various groups of patients showed that the level of these markers reflected the severity and acuteness of the pathological process in the brain and correlated with the characteristics of the clinical symptoms of patients. The most significant for an objective assessment of the clinical status of patients and the prognosis of the course of the disease are not individual inflammatory markers, but their combinations and ratios. It was found that the quantitative change in immunological parameters was ahead of the change in clinical indicators, confirming their prognostic significance. Elevated blood markers at the stages of the disease, preceding the development of pronounced clinical symptoms, can serve as an objective criterion for the presence of a current pathological process in the brain of patients with a high risk of manifestation of endogenous psychosis. The conducted immunological studies using the “Neuro-Immuno-Test” technology revealed different activation of the immune system in patients with cognitive impairment of varying severity, i.e. from mild cognitive impairment to dementia in Alzheimer's disease (AD). Conclusion: differences in immunophenotypes, which have certain quantitative and qualitative features of the spectrum of inflammatory and autoimmune markers, found using the “Neuro-Immuno-Test”, are extremely important both for diagnosis and prognosis, and for therapy optimization.

Background: depressive disorders remain an important medical problem and present significant economic and social burden on the health care system. This sets the task for the scientific community to increase the level of their detection, treatment and prevention. It seems promising to study the role of markers of neuronal disorders, in particular, proteins S-100, MBP, GFAP, in the pathogenesis of primary and recurrent depressive disorders.Purpose of the study: to determine the relationship between clinical and psychopathological characteristics of depressive disorders (anxiety, depression, aggressiveness) with markers of neuronal damage (S-100, MBP, GFAP) in primary Depressive Episode (DE) and Recurrent Depressive Disorder (RDR).Patients and methods: the study participants were 43 patients of the Mental Health Research Institute of the Tomsk National Research Medical Center Clinics with diagnoses DE (F32; n = 26) or RDR (F33; n = 17) according ICD-10. Clinical and psychopathological examination of patients with psychometric tools HDRS-17, HARS, BDHI and sampling of biological material for the study of blood serum biological markers were carried out upon admission before the start of active psychopharmacotherapy. Statistical analysis was performed using the IBM SPSS Statistics 25 program.Results: in the F32 group was found a correlation of all studied biomarkers with the severity of depressive symptoms and the hostility index according to the BDHI questionnaire (p < 0.05, Spearman).Conclusion: the relationship between markers of neuronal homeostasis disorders and various clinical and psychometric parameters is most pronounced in the case of primary Depressive Episode and is decreasing in the case of Recurrent Depressive Disorder. This may be important for the diagnostics and objectification of the severity, clinical dynamics in depressive disorders.

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Background: imbalance in the energy processes, such as oxidative phosphorylation intensity, and antioxidant systems, and impaired glutamate metabolism in the brain are important biochemical pathogenetic links in the development of schizophrenia. Changes in the activity of a number of platelet enzymes involved in these biochemical pathways were found in patients with schizophrenia.Aim: to assess the relationship between the treatment effciency of acute psychotic episode in patients with paranoid schizophrenia and the activity levels of platelet enzymes involved in energy metabolism (cytochrome c-oxidase, COX), in the antioxidant glutathione system (glutathione reductase, GR), and glutamate metabolism (glutamate dehydrogenase, GDH).Patients and methods: we examined hospitalized adult patients with a diagnosis of paranoid schizophrenia, episodic course, exacerbation of the disease (F20.01), receiving antipsychotic therapy, and healthy volunteers as a control group for assessment of control ranges for enzymatic activities. Psychometric assessment was carried out using the Positive and Negative Syndrome Scale (PANSS). Treatment response was assessed as good with a reduction in PANSS scores of 20% or more. The evaluation was performed on the first days after hospitalization and immediately before discharge.Results: 113 subjects were recruited. 50 healthy volunteers formed the control group and 63 patients, including 60 men and 3 women made up the study group. All indicators were obtained in all control group members and in 42 patients. In the group with a good treatment response, the baseline COX, GDH and GR activities proved to be significantly more often met within the control range, and the GR activity in half of the patients increased after the treatment course. In the group with insuffcient response, half of the patients had an increase in GDH activity after treatment. Of all the biochemical indices, the parameter most associated with therapeutic response was GDH activity.Conclusion: GDH activity can be considered as a possible candidate for predicting the therapeutic response to antipsychotic therapy.