[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.

[A comparative analysis of two methods for assessing the proinflammatory activity of monocytes in patients with juvenile depression]. / Sravnitel'nyi analiz dvukh sposobov otsenki provospalitel'noi aktivnosti monotsitov pri depressii u bol'nykh yunosheskogo vozrasta.

OBJECTIVE: To show that the results of evaluation of monocyte pro-inflammatory activity (PA) in patients with juvenile depression and healthy donors, obtained using a new method developed by us for counting the relative number of large monocytes on a multifunctional counter and cell analyzer, are similar to the results obtained using a standard assessment of the level of proinflammatory CD14+/CD16+ - monocytes on a flow cytofluorimeter. MATERIAL AND METHODS: The PA of monocytes, isolated from the peripheral venous blood of 18 patients with juvenile depression and 12 mentally and somatically healthy age and gender-matched persons was evaluated in two ways: using the generally accepted method of determining the relative number of monocytes with the proinflammatory phenotype CD14+/CD16+ on a flow cytofluorometer FC-500 and by counting the relative number of large monocytes on a multifunctional counter and cell analyzer Multisizer MS-4. PA of monocytes in patients was studied by using both methods in different variants: in the general group and in the subgroups of patients with low and high levels of active monocytes. RESULTS: The levels of monocyte PA determined in patients using the two methods did not statistically differ from each other in all variants of the analysis (p=0.6). The equivalence of the obtained results was confirmed by the Chi-square test (r=0.77, p=0.05), as well as by the detection of a statistically significant positive correlation between the number of monocytes with the pro-inflammatory CD14+/CD16+ phenotype, on the one hand, and the relative number of large monocytes, on the other hand (Spearman r=0.75; p<0.05). At the same time, a comparative analysis of the level of monocyte PA in the general groups of patients and healthy controls revealed significantly higher values of this indicator in patients compared with healthy persons when evaluated by both methods (p<0.05). Definition of monocytes PA using the new method developed by us for counting the relative number of large monocytes on the analyzer and cell counter is more economical and easier to perform, since it does not require the use of expensive devices and reagents, as well as complex device settings and a high level of operator qualification, as in the common method, and is carried out only by two parameters: by counting the number of large monocytes with a diameter of 12.5 to 15 microns and the total number of monocytes with a diameter of 9 to 15 microns. CONCLUSION: The proposed method for assessing monocyte PA by counting the relative number of large monocytes on the cell counter and analyzer can be used to analyze the activity of monocytes for research purposes.

[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.

[A combined marker of catatonia severity including autoimmune and thrombodynamic parameters in patients with autism spectrum disorder]. / Kombinirovannyi marker tyazhesti katatonii, vklyuchayushchii immunnye i trombodinamicheskie pokazateli, u bol'nykh s rasstroistvami autisticheskogo spektra.

OBJECTIVE: To verify a working hypothesis that thrombodynamic parameters of hypercoagulation and neuro-immune test correlate with the severity of catatonia in patients with autism spectrum disorder (ASD), and the combination of these indicators can predict the severity of catatonia with high accuracy and precision. MATERIAL AND METHODS: Twenty-four patients with ASD (22 boys and 2 girls) with infantile psychosis in childhood autism (ICD-10 F84.02) were studied. The median age of the patients was 5,5 years. Neuro-immune and thrombodynamics tests were performed. RESULTS AND CONCLUSION: Thrombodynamic parameters of clot growth rates from the activator (V, Vi and Vst) are significantly higher than their normal values. The values of the time of spontaneous clots occurrence (Tsp) are significantly less than the lower limit values for the norm (30 min). It was also shown that the activity of leukocyte elastase (LE) and the functional activity of the α1 protein inhibitor (α1-PI) are significantly higher than their normal values. The values of the levels of autoantibodies to S100 protein (aabS100B) and the basic myelin protein (aabOBM) are within the normal range. The initial clot growth rate (Vi) and the time of spontaneous clots occurrence (Tsp) significantly correlate with the severity of catatonia: Spearman's R is 0,55 for Vi (p=0,009) and -0,61for Tsp (p=0,002). Among the parameters of the neuro-immuno-test, only aabS100B indicator significantly correlates with the severity of catatonia. To increase the informative significance and accuracy of the contribution of the studied correlates of thrombodynamics and the neuro-immuno-test to the assessment of the severity of catatonia in children with ASD, a multivariate linear regression analysis was performed to construct a linear equation for the relationship between the severity of catatonia and correlates of thrombodynamics and a neuro-immuno-test. The determination coefficient R2, which determines the informational significance of the regression model, is 0,63. The remaining 37% is explained by unaccounted and not yet known factors.

[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 hypercoagulation of blood in children with childhood autism and schizophrenia]. / Trombodinamicheskie pokazateli giperkoaguliatsii krovi u detei s detskim autizmom i detskoi shizofreniei.

AIM: To detect blood plasma coagulability in children with mental diseases using a thrombodynamics test. MATERIAL AND METHODS: The study included two groups of children. Group 1 included 11 patients with infantile psychosis in autism (F84.02) (4 girls and 7 boys). Group 2 included 8 patients with childhood schizophrenia (F20.8xx3) (4 girls and 14 boys). A test was performed with T-2 Thrombodynamics analyzer (LLC Hemacore, Moscow, Russia). RESULTS: Thrombodynamic parameters, such as initial, steady-state velocity and spontaneous clots adjusted velocity (Vi, Vst and V, µm/min, respectively) and clot size at 30 minute of thrombodynamics test (CS µm) were significantly increased in the total group of patients (n=29). The time of appearance of spontaneous clots (Tsp), the time of clot lag time (Tlag) and clot density (D) did not differ significantly from the normal values (p=0.98; p=0.27 and p=0.21, respectively). In the autism group (n=11), Vi, Vst and V were significantly higher than normal values, while CS, Tsp, Tlag and D did not differ from norm. In the schizophrenia group (n=18) V, Vst and CS, and Vi were significantly increased. Tsp, Tlag and D did not differ from normal values. Differences between the parameters of thrombodynamics in 1 and 2 groups were not statistical significant. CONCLUSION: It was shown for the first time that clotting (hypercoagulability) of the blood plasma in patients with autism and childhood schizophrenia was increased. This can cause thrombosis in small vessels of the brain. Early spontaneous clots appear in many patients that indicating the presence of systemic inflammation, possibly associated with an exacerbation of neuroinflammation. The thrombodynamics test allows detection of predisposition to hypercoagulability in the early stages when other methods are not sensitive enough.

[Thrombodynamic correlates of catatonia severity in children with autism]. / Trombodinamicheskie korreliaty tiazhesti katatonii u detei s autizmom.

AIM: To study a correlation between the values of thrombodynamics parameters of hypercoagulation measured by the thrombodynamics test and the severity of catatonia in children with infantile psychosis in childhood autism (F84.02). MATERIAL AND METHODS: Twenty-four patients (22 boys and 2 girls) aged from 3 to 13 years, were studied. The severity of catatonia was determined by BFCRS. A thrombodynamic test was performed in platelet-free plasma using the analyzer T-2 Thrombodynamics Device (Hemacore LLC, Russia). RESULTS: Thrombodynamic (TD) parameters of clot growth rates from the activator (V, Vi and Vst) were statistically significantly higher than normal values. Similar results were obtained for Clot Size at 30 min (CS, µm): Tlag and D values were within normal limits. The values of Time of appearance of spontaneous clots (Tsp min) were less than the lower limit values for the norm (30 min). Correlation analysis showed that the severity of catatonia is positively correlated with the initial clot growth rate (Vi) (p=0.009) and negatively with Tsp (p=0.002). With an increase in the time of appearance of spontaneous clots (due to a decrease in the procoagulant activity of platelet microparticles in the plasma of patients), the severity of catatonia in children with ASD decreases. CONCLUSION: The results suggest that normalizing plasma and platelet hemostasis is important for increasing the effectiveness of treatment of patients with ASD with catatonia.

[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.

[Risk assessment of thrombotic events in patients with schizophrenia and schizoaffective disorder in the acute state: the 'fibrinodynamics' technology]. / Otsenka riska tromboticheskikh narushenii u bol'nykh shizofreniei i shizoaffektivnymi rasstroistvami v ostrom periode bolezni s ispol'zovaniem tekhnologii 'fibrinodinamika'.

AIM: To assess the risk of thrombotic events in patients with schizophrenia and schizoaffective disorder based on 'fibrinodynamics' technology. MATERIAL AND METHODS: A group of 76 women, including 38 with paranoid schizophrenia (F20.0), 18 with schizoaffective disorder (F25.1) in the acute stage, and 20 healthy controls, participated in the study. The technology includes the study of coagulation and fibrinolysis, Karmin author software, and calculation of peak time and hemostasis potential of spontaneous clots. Growth and lysis of fibrin clots were studied in plasma purified from platelets. All preanalytic procedures were conducted within 30 minutes after blood sampling. Blood serum was studied separately using the neuroimmunological test. Dynamic of brightness profiles of the clots was determined and a number of parameters (peak time and hemostasis potential of spontaneous clots) were calculated using the Karmin software. RESULTS: In patients with schizophrenia, the dynamic brightness profile of the clots has two peaks: the first peak is formed as a result of the growth and lysis of the clot initiated by the activator, the second peak is due to the growth and lysis of spontaneous clots in the volume of the measuring cuvette far from the activator. In healthy donors, the second peak under experimental conditions is absent. In the group of schizophrenic patients, a strong negative correlation is observed between the peak time of the second peak and the activity of leukocyte elastase (Spearman R = -0.75, p<0.0001), i.e. the greater the activity of elastase, the earlier the maximum of the second peak is formed and vice versa. In the control group, there is no such correlation. Evaluation of the potential of hemostasis of spontaneous clots showed that in 42% of schizophrenic patients this parameter is shifted above the norm, which indicates an increased risk of thrombosis of small brain arteries in these patients. CONCLUSION: The developed technology of 'fibrinodynamics' has a good potential for introduction into personalized medicine to identify increased risks of thrombosis of small cerebral vessels in patients with acute schizophrenia leading to the development of cognitive disorders and to control the normalization of hemostasis with antiplatelet or anticoagulant drugs.

Complement-Mediated Death of Ciliate Tetrahymena pyriformis Caused by Human Blood Serum.

Toxicity of human blood serum for ciliate Tetrahymena pyriformis is determined by the complement system. When ciliate are dying after being exposed to blood serum, cell membrane permeability for low-molecular-weight compounds significantly increases, probably due to pore formation. Serine protease inhibitors or exposure to physical factors inducing complement inactivation (e.g., heating up to 56°C) completely prevented ciliate death under the effect of human serum. Activation of serum complement upon interaction with Tetrahymena cells occurred by the classical or lectin pathway, while the contribution of the alternative activation pathway was negligible.

[Ultrastructural changes in platelets and their relationship with serotonin metabolism in patients with schizophrenia treated with olanzapine].

An aim of the study was to investigate the effect of olanzapine treatment on platelet ultrastructure and to search for its association with serotonin metabolism in patients with schizophrenia. Platelets of 59 patients with chronic (attack-like schizophrenia) treated with olanzapine and 31 health people were explored. Based on the data on the platelet ultrastructure, authors studied the content of functionally activated vacuolated platelets (VP) and less active granular platelets (GP) as well of platelet serotonin (PS). VP content was higher in patients compared to the control group (+57%, p<0.001). After treatment for 8 and 28 weeks with olanzapine, it decreased and reached the control level (52% and 57%, respectively). There were significant negative correlations between % VP and PS before treatment (r= -0.30, p=0.02) and 8 week after treatment (r= -0.29, p<0.04) and a positive correlation between the decrease in % VP and increase in the PS levels during 8-week treatment (r=0.34, p=0.008). The association between increased platelet vacuolization and decreased PS content in schizophrenia was demonstrated for the first time. This association disappeared after treatment that led to the normalization of % VP and PS levels.

[The effect of serotonin on the cytotoxic activity of natural killer lymphocytes in patients with the first episode of endogenous psychosis].

Authors studied the level of cytotoxic activity of natural killer lymphocytes (NKCA) and the effect of monocytes, serotonin, rate of serotonin reuptake by lymphocytes and psychotropic therapy on NKCA levels in 59 male patients, aged 18-30 years, with the first episode of attack-like progressive schizophrenia (33 patients) and schizoaffective psychosis (26 patients). All patients were examined at baseline, 4 and 8 weeks after the beginning of treatment with haloperidol and clozapine. Before the treatment, the decrease of NKCA was found in a half of patients compared to controls. In other patients, the NKCA levels were high and did not differ from those in controls. The treatment resistance was estimated as 70,6% in patients with schizophrenia with initially low NKCA levels and 30,8% in patients with schizoaffective psychosis with initially low NKCA levels. During the treatment, the initially high NKCA level decreased while the initially low level increased but remained lower compared to controls. These changes suggest the active reaction from the immune system of the patient to treatment with neuroleptics. The changes of NKCA values during the treatment were reciprocally related to the maximal rate of serotonin reuptake by lymphocytes. Serotonin added to the cell culture in vitro normalized the NKCA level in cultures with- and without monocytes. This effect was revealed in both pathologies only in responders, regardless of the presence or absence monocytes, that may be explained by the presence of active serotonin receptors on the NK cell surface in these patients.

[Pathogenetic characteristics of post stroke affective disorders].

Fifty patients with affective disorders developed after first cerebral stroke were studied. A spectrum of affective disorders included post-stroke depressions, generalized anxiety disorders, anxiety-depressive disorders and pseudo post-stroke depressions. Platelet serotonin (PS) levels were measured in these patients as well. The levels of PS at the first three days after stroke and their changes towards the 28th day are associated with the development of post-stroke affective disorders. The development of anxiety-depressive disorders in the acute period of stroke is related to the localization of brain lesion focus. The low levels of PS in patients at the first three days after stroke may be the risk factor of delayed affective disorders development.

[Functional siate of serotoninergic system and the 5-HTTLPR polymorphism of the serotonin transporter gene in patients with schizophrenia].

Blood serotonin concentration is thought to regulate behavior and may be implicated in the development of psychopathological symptoms as well. Serotonin transporter regulates the levels of serotonin by the reuptake of this neurotransmitter from the synaptic cleft. In this study we compare the platelet serotonin concentration and constant V(max) value in patients with schizophrenia and healthy controls with different 5-HTTLPR genotypes. The study included 60 patients and 62 controls. Biochemical parameters mentioned above were associated with a 5-HTTLPR genotype. Carriers of the LL genotype had lower serotonin blood concentration and V(max) compared to genotypes containing one or two copies of an S allele both in patients and controls. The results obtained suggest that the genetic variant may contribute to the state of serotoninergic system.

[Platelet serotonergic parameters and clinical symptoms of psychosis in patients with episodic progressive schizophrenia].

A sample included 59 patients, 38 males and 21 females, mean age (M+/-SD) 33,4+/-10,2 years, age-at-onset 26+/-9,5 years, illness duration 7,8+/-6,1 years, with episodic progressive schizophrenia (ICD-10: schizophrenia, paranoid type, F20.0) with continuous course at the stage of exacerbation. Clinical symptoms were assessed using the PANSS. Platelet 5-HT content, 3H-serotonin uptake (Vmax), 3H-imipramine receptor density (Bmax), high- and low molecular weight human serotonin platelet transporter protein immunoreactivity (HMW-SERT and LMW-SERT values) were measured. The most frequent psychotic symptoms were delusions, conceptual disorganization and hallucinations, with the majority of patients experiencing from one to three symptoms. A significant increase of platelet 5-HT content and 3H-imipramine receptor density (Bmax) was found in male patients. In the male group, delusions, conceptual disorganization and hallucinations as well as PANSS psychotic cluster scores were correlated positively with 5-HT content and negatively with HMW-SERT and LMW-SERT values. Possible reasons of the differences in correlations of platelet 5-HT serotonin and serotonin transporter values with psychotic symptoms are discussed. The results are additional evidence for the involvement of serotonergic dysfunction in the pathogenesis of schizophrenic psychoses. They confirm the usefulness of testing of platelet 5-HT content and SERT immunoreactivity as biological markers of schizophrenic psychoses, in particular for male patents.

[Parameters of platelet serotonin system in patients with schizophrenia treated with olanzapine: a search for the serotonergic predictors of therapeutic efficacy].

Fifty-nine patients, 21 women and 38 men, with ICD-10 diagnosis of schizophrenia (F20.0), attack-like type, were treated with olanzapine during 28 weeks (8-weeks of acute and 20-weeks of maintenance therapy). Evaluation of clinical symptoms measured by the Positive and Negative Syndromes scale (PANSS) revealed that female patients responded better to therapy as compared to male ones, with PANSS total, PANSS negative and PANSS general psychopathological scores being significantly reduced (p < 0.006) in females after 1 week of the treatment and in males--after 2 weeks. In the female group, a reduction of PANSS total score by 50% in the acute stage of treatment qualified as a very good response was observed in 7 (33%) patients and in the male group--in 1 (2.7%). The between-groups difference was highly significant (p = 0.002). When examined for a rate of 3H-serotonin uptake into platelets, density of sites of 3H-imipramine binding on the whole platelets, platelet serotonin level and levels of high- also low-molecular weight forms of platelet immunoreactive serotonin transporter protein, a significant decrease of the platelet serotonin level, comparing to controls, was detected in the female group before treatment. During the treatment, this parameter gradually increased up to control level. Other parameters did not change significantly for 28-weeks of therapy and did not differ from the control values. There were positive correlations between the levels of platelet serotonin before treatment and subsequent reduction of the PANSS total and positive subscale scores in the female group. In responders with a very good treatment-related response, the serotonin level in the platelets before treatment was higher compared to the values in resistant patients: 5.4 +/- 2.5 and 2.7 +/- 1.3 nmol/10(9) cells, respectively. Relative risk (RR) of unfavorable treatment outcome in patients with initially reduced levels of platelet serotonin was approximately twice lower (RR = 1.83; Cl 95% 1.1-34.9) than that in patients with normal or elevated levels of platelet serotonin. The results suggest that selection of patients with initial higher level of platelet serotonin before olanzapine treatment can reduce the risk of non-responding to therapy by 36%.

[Levels and molecular heterogeneity of serotonin transporter protein in platelets of patients with different mental diseases: a comparative analysis with the use of monoclonal and polyclonal antibodies]. / Soderzhanie i molekuliarnaia geterogennost' belka--perenoschika serotonina v trombotsitakh bol'nykh s razlichnymi psikhicheskimi zabolevaniiami: sravnitel'nyi analiz s ispol'zovaniem monoklonal'nykh i poliklonal'nykh antitel.

Polyclonal (PAb) and monoclonal (MAb) antibodies to CT2-epitope of the C-terminal fragment of serotonin transporter (SERT) protein were used to study the levels and molecular heterogeneity of platelet SERT in healthy donors and patients with affective (AD) and somatoform (SD) disorders, schizoaffective disorder (SAD) and schizophrenia. SERT was found to exist as high molecular wight (HMW) and low molecular weight (LMW) forms separated after electrophoresis. The levels of HMW and LMW forms of SERT were significantly, decreased in mentally ill patients as compared to healthy individuals. Unlike PAb, horse radish peroxidase (HRP)-conjugated MAbs were more sensitive and specific to SERT and could detect the LMW form of SERT as a duplet protein form with MW about 40 and 43 kDa. The MAb to CT2 C-terminal fragment of SERT conjugated with HRP is considered to be a new valuable tool for further investigation of SERT expression, properties, and posttranslation modification in the controls and in patients with different psychopathology.

[Specific aspects of thrombocyte system of serotonin in patients with different manifestations of schizoaffective psychosis]. / Osobennosti serotoninovoi sistemy trombotsitov bol'nykh s razlichnymi klinicheskimi proiavleniiami shizofaffektivnogo psikhoza.

45 women with different manifestations of schizoaffective psychosis (SAP) were examined. The diagnosis corresponded to ICD-10 (F25). According to the classification elaborated in Mental Health Research Centre of Russian Academy of Medical Sciences, groups of patients were identified with different variants of the psychoses course: a nuclear SAP type; a borderline SAP variation with phasic-recurrent course; SAP with progredient variation (schizoaffective variation of schizophrenia). The patients were examined both during the attack and remission. A rate of serotonine uptake (Vmax) in blood platelets, a specific imipramine binding (Bmax) and the level of serotonin in blood platelets were evaluated. It was found that dynamics of both Vmax and the level of serotonin in different SAP types were different, that was related to clinical and biological SAP heterogeneity. A tendency to decreasing of serotonin system functional activity was found in progredient SAP variations, especially during the remission, which was of low quality in these cases. On the contrary, in the borderline variations the indices of the decreased function of serotonin system corresponded well to those of acute psychosis. In nuclear type--a type with the most favourable course of psychosis--any significant changes weren't revealed as compared with the normal parameters.