[Prolonged and chronic endogenous manic and manic-delusional states (psychopathology, typology, dynamics, clinic)]. / Zatyazhnye i khronicheskie endogennye maniakal'nye i maniakal'no-bredovye sostoyaniya (psikhopatologiya, tipologiya, dinamika, klinika).

OBJECTIVE: A clinical and psychopathological analysis, nosological differentiation of prolonged and chronic manic and manic-delusional states (PMDS) within the framework of the paroxysmal course of endogenous psychoses, determination of the patterns of their development, diagnostic criteria and prognosis. MATERIAL AND METHODS: The study included 76 female patients (average age 37.2±8.3 years) who were hospitalized for endogenous mental illnesses with a paroxysmal course that occurred with the clinical picture of PMDS. The patients were divided into two groups: clinical (n=43) and follow-up (n=33). Clinical-psychopathological, clinical-follow-up, psychometric, statistical methods were used. RESULTS: A clinical and dynamic typology of PMDS has been developed, according to which 2 groups have been identified: «monomorphic¼ PMDS and «polymorphic¼ PMDS. «Monomorphic¼ PMDS included 2 subtypes - «acute¼ and «chronified¼ and were characterized by the same clinical picture that remained unchanged throughout, while «polymorphic¼, which also included 2 subtypes - «developing¼ and «double mania subtype¼, were characterized by the variability of clinical picture. «Acute¼ and «developing¼ subtypes of PMDS predominantly developed in schizoaffective psychosis and bipolar disorder; the «chronified¼ subtype and the «double mania¼ subtype were more often observed within the framework of the schizoaffective variant of paroxysmal-progressive schizophrenia. CONCLUSION: The clinical and dynamic structure of PMDS is heterogeneous and differs in psychopathological structure, as well as in the level of stability of symptoms and characteristics of its course. The developed clinical typology of PMDS is prognostically significant and provides information about the further dynamics of the disease.

[Proinflammatory activity of monocytes and activity of glutathione-dependent enzymes in red blood cells in women with depressive conditions]. / Provospalitel'naya aktivnost' monotsitov i aktivnost' glutation-zavisimykh fermentov v eritrotsitakh krovi u zhenshchin s depressivnymi sostoyaniyami.

OBJECTIVE: To search for possible connections between the anti-inflammatory activity of monocytes (PAM) and the activity of glutathione metabolic enzymes: glutathione reductase (GR) and glutathione-S-transferase (GT) in patients with depressive states (DS) within various mental pathologies, as well as between the studied biological parameters and clinical condition of patients. MATERIAL AND METHODS: Sixty-one women, aged 18-56 years, with DC were examined before and after treatment. Symptom severity was assessed using the Positive and Negative Syndrome Scale (PANSS) and the Hamilton Depressive Symptom Rating Scale (HDRS-21). The control group included 23 women of the corresponding age without mental pathology. Biological parameters were assessed in the peripheral blood of patients and healthy people. RESULTS: Patients with a high level of PAM compared to the control (p<0.001) (subgroup 1, n=31) and with a low (at the control level) level (subgroup 2, n=30) were identified. In the subgroup 1, the values of GR and GT were significantly lower than in patients of subgroup 2 (p<0.05 and p<0.01, respectively). Negative correlations between the level of PAM before treatment and GR before and after treatment were revealed in patients who responded to treatment (r=-0.67; p=0.0041; r=-0.76; p=0.0001). CONCLUSION: The results may indicate the inverse relationship between the level of PAM and the activity of GR and GT, which are involved in the pathogenesis of DC, and can also serve as criteria for assessing the response of patients to treatment.

[Features of the neurocognitive profile of patients with protracted and chronic endogenous manic and manic-delusional states]. / Osobennosti neirokognitivnogo profilya bol'nykh s zatyazhnymi i khronicheskimi endogennymi maniakal'nymi i maniakal'no-bredovymi sostoyaniyami.

OBJECTIVE: To study the neurocognitive profile of patients with protracted and chronic endogenous manic and manic-delusional states (EMDS). MATERIAL AND METHODS: Thirty-two female patients, aged 18 to 55 years (mean age 36.2±10.2 years), with protracted and chronic EMDS were studied. Based on the clinical typology of EMDS, patients were divided into 4 groups of 8 patients each: group 1 - «acute¼ subtype, group 2 - «chronified¼ subtype, group 3 - «developing¼ subtype and group 4 - subtype «double mania¼. Neuropsychological, clinical-psychopathological and statistical methods were used. RESULTS: Disturbances of regulatory and executive functions and a decrease in neurodynamic indicators of mental activity in patients with EMDS are significantly more pronounced compared with the control group (p<0.05). The values of the index of severity of disturbances of regulatory and executive functions in patients with EMDS range from 0.95 points (group 1) to 1.14 points (group 4), without statistically significant differences between the groups. The highest severity of neurodynamic disorders is observed in group 1 (1.88 points), while in other groups the index values range from 0.88 points in group 2 to 1.09 in group 4 (p<0.05). Patients of group 1 have greater severity and wider spectrum of neurodynamic symptoms compared with group 2 (U=45.00; p<0.0021), group 3 (U=30.00; p<0.04), and group 4 (U=45.00; p<0.001). It should be noted that the cognitive impairments identified in patients with EMDS did not reach the level of dementia. CONCLUSION: The most characteristic of EMBS are cognitive impairments associated with a decrease in the parameters of the neurodynamics of mental activity related to the first functional block, as well as with deficiency of executive functions, impaired planning and organization of cognitive activity, due to the weakness of the structures of the third functional block.

Clinical-Immunological Correlates in Post-COVID-19 Endogenous Psychoses.

Objectives. To carry out a clinical and immunological study of the potential impact of coronavirus infection on the course of endogenous psychoses. Materials and methods. A total of 33 female patients aged 16-48 years with depressive-delusional states (F20.01, F21, F31) developing after coronavirus infections took part; group 1 consisted of 15 people who developed depressive-delusional states 1-2 months after COVID-19; group 2 consisted of 18 people with similar psychoses developing at later time points (2-6 months). The severity of psychopathological symptoms was assessed using the PANSS and HDRS-21 scales. The activity of inflammatory markers leukocyte elastase (LE) and α1-proteinase inhibitor (α1-PI) was determined in patients' blood. Absolute neutrophil and lymphocyte contents and their ratio (the neutrophil:lymphocyte index) were also evaluated. Standard values for indicators from healthy donors corresponding to patients in terms of age and sex were used as control values. Results. Endogenous psychosis developing at longer intervals after coronavirus infection (group 2) was found to be associated with "typical" inflammatory reactions, with increases in the activity of acute-phase proteins (α1-PI: 43.0 (35.6-49.7) IU/ml, p = 0.001) and neutrophil degranulation activity (LE - 254.8 (238.0-271.0) nmol/min·ml, p < 0.001), which was associated with the development of depressive-delusional states with dominance of manifestations of positive affectivity (anxiety, melancholy) and the extended nature of delusional disorders, which were mostly incongruent to affect. Conversely, development of endogenous psychosis during the first two months after COVID-19 (group 1) was characterized by a spectrum of inflammatory biomarkers with a decrease in neutrophil count ((2.6 ± 0.9)·109/liter, p < 0.05) and low LE activity (196 (172-209.4) nmol/min·ml, p < 0.001). This immunological profile was associated with predominance of manifestations of negative affectivity (apathy, asthenia, adynamia) in the structure of depressive-delusional states and the relatively undeveloped nature of delusional disorders, which were predominantly congruent to affect. Conclusions. The clinical and biological correlates found here presumptively indicate that experience of COVID-19 infection has a modulatory effect on neuroinflammation and the structure of endogenous psychosis.

[Cinnabarinic acid as a potential prognostic marker of schizophrenia]. / Tsinnabarinovaya kislota kak potentsial'nyi prognosticheskii marker shizofrenii.

OBJECTIVE: To develop a method for determining cinnabarinic acid (CA) and its immediate precursor 3-hydroxyanthranylic acid (3HAA) in blood plasma and to study their concentrations in patients with schizophrenia before and after treatment. MATERIAL AND METHODS: The study was carried out on a sample of 23 female patients with an attack-like progredient schizophrenia (F20.01). The levels of CA and 3HAA in blood plasma were measured using liquid chromatography with tandem mass spectrometry. RESULTS: We found an inverse statistically significant correlation of the sum of CA and 3HAA concentrations before treatment with the total PANSS score after treatment (R=-0.50; p<0.05). There was also an inverse correlation of the CA concentration of before treatment with the total PANSS score after treatment (R=-0.41, p=0.052), statistically significant at the trend level (0.05

[Evaluation of the levels of proinflammatory activity of monocytes in depressed patients with schizophrenia]. / Provospalitel'naya aktivnost' monotsitov u bol'nykh s depressivnymi sostoyaniyami v ramkakh shizofrenii.

OBJECTIVE: To evaluate the proinflammatory activity of monocytes (PAM) in depressed patients with schizophrenia by counting the proinflammatory monocyte number and to identify possible correlations between PAM and clinical indicators. MATERIAL AND METHODS: Sixty-eight women with depressive states in schizophrenia and 23 mentally and somatically healthy age- and sex-matched people were examined. The clinical condition of the patients was assessed by the total PANSS (PANSS_tot) and HDRS (HDRS_tot) scores. PAM was determined in the peripheral blood of patients and healthy controls by counting the number of large monocytes with a diameter of 12.5 to 15 microns on a cell counter and analyzer using the positive magnetic separation method to isolate a pure population of CD14 monocytes. RESULTS: Before treatment, the level of PAM significantly exceeded the corresponding value in controls (p<0.001) in half of the patients; after treatment, the level of PAM decreased to control values (p<0.001). Linear regression revealed in a subgroup of patients with an initially low PAM level a positive correlation between its value and HDRS tot (r=0.5, p<0.05) before treatment, that is, a low PAM level before treatment was accompanied by low-severity depressive disorders. The analysis of PAM level in the subgroups of patients responding and not responding to treatment revealed a decrease in the PAM value after treatment in the responding patients assessed by PANSS_tot (p<0.05) and in the responding patients assessed by HDRS_tot (p=0.06). Similar patterns were not detected in the subgroups of nonresponders. CONCLUSION: The correlations between the PAM level and the severity of depressive and other psychopathological disorders in patients with depressive states in schizophrenia may indicate the involvement of immune inflammation in the pathogenesis of this disease. The positive relationship between the initially low PAM level and the mild severity of depressive disorders can be used as a prognostic sign of patients' response to treatment.

[Clinical and immunological correlates in endogenous psychoses developed after COVID-19]. / Kliniko-immunologicheskie korrelyaty pri endogennykh psikhozakh, razvivshikhsya posle perenesennogo COVID-19.

OBJECTIVE: The clinical and immunological study of the potential impact of coronavirus infection on the course of endogenous psychosis. MATERIAL AND METHODS: Thirty-three female patients, aged 16 to 48 years, with depressive-delusional conditions (ICD-10 F20.01, F21, F31) developed after coronavirus infection, of whom 15 people (group 1) had depressive-delusional states 1-2 months after COVID-19 and 18 people (group 2), who developed similar psychoses in later periods (2-6 months). The severity of the psychopathologic symptoms was evaluated with PANSS and HDRS-21 scales. The activity of inflammatory markers - leukocyte elastase (LE) and α1-proteinase inhibitor (α1-PI) in the blood was determined. The absolute neutrophil count, the absolute lymphocyte count and the neutrophil/lymphocyte ratio were calculated. As a control, we used standard values of indicators of age - and sex-matched healthy donors. RESULTS: The endogenous psychosis that developed later after a coronavirus infection (group 2) is associated with a "typical" inflammatory reaction with an increase in the activity of acute phase proteins (according to α1-PI) and degranulation activity of neutrophils (according to LE), which is associated with the development of depressive-delusional states in patients with the dominance of manifestations of positive affectivity (anxiety, melancholy) and the extended nature of delusional disorders, which were predominantly incongruent to affect. On the contrary, the development of endogenous psychosis during the first two months after COVID-19 (group 1) is characterized by a spectrum of inflammatory biomarkers with a decrease in the number of neutrophils and low activity of LE. This immunological profile is associated with the predominance of manifestations of negative affectivity (apathy, asthenia, adynamia) in the structure of depressive-delusional states and the relatively undeveloped nature of delusional disorders, which were predominantly congruent to affect. CONCLUSION: The clinical and biological correlates presumably indicate the modulating effect of the coronavirus infection (COVID-19) on neuroinflammation and the structure of endogenous psychosis.

[The decrease in procoagulant activity of blood during combined therapy with antidepressants and antipsychotics in patients with endogenous mental disorders]. / Snizhenie prokoagulyantnoi aktivnosti krovi u bol'nykh s endogennymi psikhicheskimi rasstroistvami pri kombinirovannoi terapii antidepressantami i antipsikhotikami.

OBJECTIVE: To compare the changes in thrombodynamics indices in two groups of patients with endogenous mental disorders before and after combined treatment with antipsychotics and antidepressants (AD + group) and those who did not receive antidepressants (AD-group). MATERIAL AND METHODS: The study included 110 patients, aged from 16 to 60 years (median age [Q1; Q3] 29 years [22; 35]), admitted for inpatient treatment at the clinic of Mental Health Research Center with the following mental disorders: schizophrenia with attack-like/attack-progressive/continuous type of course (F20.00-2), schizotypal disorder with affective fluctuations (F21.3-4), affective disorder (F 31.1-5; F 32.0-3; F 33.0-3). The thrombodynamics test (TD) was carried out on a T-2 thrombodynamics device according to the manufacturer's instructions (Hemacore LLC, Moscow, Russia). RESULTS: In patients with endogenous mental disorders after combined therapy with antidepressants and antipsychotics, a statistically significant decrease in the procoagulant activity of plasma and procoagulant spontaneous clots is observed, which indicates a decrease in the severity of systemic, immune inflammation. In patients with endogenous mental disorders after antipsychotic therapy without the addition of antidepressants, for most thrombodynamic parameters, there is no statistically significant decrease in procoagulant plasma activity and spontaneous clots formation. It indicates the persistence of acute systemic, immune inflammation in this group. CONCLUSION: The statistically significant positive change in plasma and platelet hemostasis may testify that combined treatment with antipsychotics and antidepressants in patients with endogenous mental disorders may be a biological, pathogenetic link that promotes augmentation (extended action) of antipsychotic therapy.

[Application of machine learning for predicting the outcome of treatment of patients with schizophrenia according to the indicators of «Thrombodynamics¼ test]. / Primenenie mashinnogo obucheniya dlya prognozirovaniya iskhoda lecheniya bol'nykh shizofreniei po pokazatelyam testa «Trombodinamika¼.

OBJECTIVE: To identify relationships between thrombodynamic values and the severity of the condition in patients with schizophrenia spectrum disorders (SSD) before and after treatment. MATERIAL AND METHODS: The study included 92 patients in an acute state of schizophrenia or schizotypal disorder, aged 16 to 57 years (median age [Q1; Q3] - 25 years). All patients received complex psychopharmacotherapy adequate to their psychopathological state. The PANSS was used to assess the severity of symptoms in patients. The coagulation parameters were determined by the thrombodynamics test, in which the growth of fibrin clots in platelet free plasma are observed from special activator. The patient population was divided into two groups with weak and strong response to treatment. Data analysis included machine learning (ML) techniques: logistic regression, random forests, decision trees, support vector machines with radial basis functions, statistically weighted syndromes, permutation method. RESULTS: An analysis using permutation method revealed statistically significant different thrombodynamics values between groups of patients with weak and strong responses. There are significant differences between thrombodynamics values: T1D, T2D, T2Tlag and DTlag, and values characterizing the severity of positive symptoms before and after treatment (T1PposTot, T2PposTot), severity of psychopathological symptoms before treatment (T1Ppsy1, T1Ppsy6, T1Ppsy13). All ML techniques showed the relationship between thrombodynamics values and response to treatment. The best statistical significance was for statistically weighted syndromes method. CONCLUSION: The combination of the results of different ML techniques at a high level of statistical significance identifies the thrombodynamic predictors of weak effect of treatment of SSD.

[Correlations between thrombodynamic parameters of coagulation and negative syndromes in patients with schizophrenia]. / Korrelyatsionnaya svyaz' trombodinamicheskikh pokazatelei koagulyatsii i negativnykh sindromov u bol'nykh shizofreniei.

OBJECTIVE: To identify a possible correlation between parameters of thrombodynamic coagulation and negative syndromes in patients with schizophrenia. MATERIAL AND METHODS: The study included 148 female inpatients, aged 16 to 57 years, with the following mental disorders: schizophrenia with attack-like/attack-progressive/continuous type of course (F20.00-2), schizotypal disorder with affective fluctuations (F21.3-4). The thrombodynamics test (TD) was carried out on a T-2 thrombodynamics recorder (Hemacore LLC, Moscow, Russia). RESULTS: A positive correlation was shown between the thrombodynamic parameters of clot growth rates (V, Vst, and Vi), clot size at the 30th minute (CS), and the total severity of negative syndromes (PANSS). There is a negative correlation between the time of spontaneous clots (Tsp) and the total severity of negative syndromes in patients. Positive correlations of V and Vst with scores on the fourth (Passive/apathetic social withdrawal), fifth (Difficulty in abstract thinking) and seventh (Stereotyped thinking) items of the PANSS negative subscale were revealed. There is a negative correlation between Tsp and the score on the 7th item, i.e. a shorter time for the appearance of spontaneous clots corresponds to a more pronounced Stereotyped thinking in patients. CONCLUSION: For the first time, correlations between thrombodynamic indicators of hypercoagulation and negative syndromes in patients with schizophrenia are identified, which emphasizes the need to normalize hemostasis to prevent further aggravation of these disorders.

[Reduction of plasma procoagulant activity in patients with schizophrenia during pharmacotherapy: thrombodynamic parameters of coagulation before and after treatment]. / Snizhenie prokoaguliantnoi aktivnosti plazmy krovi bol'nykh shizofreniei pri farmakoterapii: trombodinamicheskie pokazateli koaguliatsii do i posle lecheniia.

AIM: To detect plasma procoagulant activity in patients with schizophrenia at admission to the hospital in a state of exacerbation before (point 1) and after (point 2) pharmacotherapy and evaluate plasma and platelet hemostasis abnormalities. MATERIAL AND METHODS: The study included 80 women, aged from 16 to 57 years, median age 28 years, with schizophrenia with continuous, paroxysmal-progressive or paroxysmal course (F20.00, F20.01, F20.02 according to ICD-10). In 42 of 80 patients, depressive disorders in the structure of schizophrenia were observed. The thrombodynamic test (TD) was performed on T-2 Trombodynamis device according to the manufacturer's instructions (Hemacore LLC, Moscow, Russia). Blood for the TD test was taken in admission to the hospital (point 1) and on discharge (point 2). All patients received standard pharmacotherapy according to their condition. RESULTS: For the first time, it was established that in the whole group of patients (n=46) thrombodynamic indicators of the rate of growth of the clot: initial velocity (Vin), stationary velocity (Vst) and adjusted for spontaneous clots velocity (V) and the amount of clot for 30 minutes test TD (ClotSize, CS) were significantly higher compared to normal values. The mean time of occurrence of spontaneous thrombosis (Tsp) was significantly less than 30 min (p<0.0001), indicating rapid, spontaneous thrombosis. Other parameters of TD did not differ significantly from the norm. As a result of treatment, the initial growth rate of the clot from the activator (Vi) decreased from 58,5 µm/min to 54,5 µm/min; V speed from 37,4 µm/min to 33,5 µm/min; CS clot size from 1249 µm to 1219 µm; clot density - from 24 874 units up to 23 658 units. All these changes are significant. Such dynamics of plasma hemostasis clearly indicates a significant decrease in the coagulation activity of the blood plasma of patients as a result of treatment. An increase in the time of appearance of spontaneous clots after treatment (from 23.5 minutes to 30.5 minutes) indicates a decrease in the procoagulant activity of platelet microparticles after treatment, i.e. the reduction of platelet activation as a result of treatment. CONCLUSION: Our studies have shown for the first time that treatment of patients with antidepressants and antipsychotics reduces the generation of spontaneous clots. The treatment of patients with schizophrenia is accompanied by a decrease in the activity of plasma and platelet hemostasis. This is of great practical importance, since hypercoagulation of spontaneous clots in schizophrenic patients aggravates their chronic inflammatory disorders and affects their resistance to treatment.

[Thrombodynamic parameters of hypercoagulability in patients with affective disorder and schizophrenia in a state of exacerbation]. / Trombodinamicheskie pokazateli giperkoaguliatsii plazmy krovi u bol'nykh s affektivnym zabolevaniem i shizofreniei v stadii obostreniia.

AIM: To detect coagulability impairment of blood plasma in patients with schizophrenia or affective disease in a state of exacerbation using a thrombodynamics test. MATERIAL AND METHODS: The study included 46 women, 32 with attack-like/shift-like/or continuous schizophrenia (ICD-10: F20.00, F20.01, F20.02), 7 with schizotypal disorder (ICD-10: F21.3-21.4) and 7 with affective disorder (ICD-10: F32.00, F32.3). Thrombodynamics tests were performed on T-2 thrombodynamics analyzer ('Hemacore LLC', Moscow, Russia). RESULTS: For the first time, it was shown that in the patient population (n=46), the thrombodynamic parameters of the blood clot growth rate [initial velocity (Vi), steady-state velocity (Vst) and spontaneous clots adjusted velocity (V)] and clot size at 30 minute of thrombodynamics (Clot Size, CS) were significantly higher than normal values. The mean appearance of spontaneous clots (Tsp) was significantly lower than 30 minutes (p<0.0001) which indicated a rapid, spontaneous clots formation. The mean value of clot lag time (Tlag) and clot density (Density, D) did not differ significantly from normal values. The number of changed thrombodynamic parameters decreased in the following sequence: schizophrenia with different types of courses > schizotypal disorder>affective disorder. This is in good agreement with the fact that the course of affective disorders is more favorable than that in schizophrenia. CONCLUSION: The thrombodynamics test has a good potential for introduction into medicine to detect hypercoagulability and increased risks of thrombotic complications in patients, as well as to control for normalization of hemostasis with antiaggregant or anticoagulant drugs. Thrombodynamics makes it possible to identify a tendency to hypercoagulable states at an early stage, when other methods are still not sensitive enough. The study identified the hypercoagulability in patients with schizophrenia and affective disorders.

[A diagnostic algorithm and treatment procedure in disordered vital functions in newborns admitted to a resuscitation ward]. / Algoritm diagnostiki i taktika lecheniia narushenii vital'nykh funktsii novorozhdennykh pri postuplenii v otdelenie reanimatsii.

Total mortality decreased by 2.5 times in the wards for intensive care of the newborns in the Tushino Pediatric Hospital in 1996 and is now 7.6%. Such results are due to a complex of measures, one such measure being the development and introduction of an algorithm for the diagnosis and treatment of newborns hospitalized in intensive care wards. The algorithm facilitates the work of the staff, helps earlier diagnose a disease, and, hence, carry out timely scientifically based therapy.