[Peculiarities of Platelet Activation Changes in Patients with Chronic Schizophrenia, Depending on the Severity of Positive and Negative Symptoms during the Remission Formation].

OBJECTIVE: The aim of our study was to compare the changes in the severity of positive, negative and psychopathological PANSS symptoms which occur at an outcome of an attack in schizophrenic patients along with remission formation and the degree of platelet activation in these patients. METHODS: Psychometric scale of the Positive and Negative Syndrome Scale (PA NSS) and the method of estimation of platelet activation based on the calculation of cells number after elution from the column with sepharose CL-2B were used. RESULTS: The changes in the severity of the disease were estimated using the PANSS scale of chronic schizophrenic patients in remission formation. An increase in platelet activation was determined on the basis of the above described quantitative parameter. Comparison of changes in platelet activation parameter with changes in the disease severity rating detected similar statistically indistinguishable (p > 0.05) changes in the severity of positive symptoms and quantitative variable of platelet activation between the 1st and the 3rd visits in the period of remission formation. Platelet number after elution from the column during the 3rd visit was approximately two times less than during the 1st visit (p < 0.002). PANSS positive subscale shows a decrease of the severity of the syndrome by 1.6 times (p < 0.0002). In addition the difference between the platelet activation parameter and severity of the negative syndrome was fixed during the 3rd visit (p < 0.034). CONCLUSION: Similar changes in the severity of positive syndrome and platelet activation parameter were presented from 1st to 3rd visit in the remission formation. A distinction between the platelet activation parameter and severity of the negative syndrome was fixed during the 3rd visit.

[Platelet activity in the chronic schizophrenic patients during attacks outcome and remission development].

The purpose of this work was to evaluate the degree of activation of platelets chronically schizophrenic patients with paroxysmal course of the disease during outcome from the attack of disease or in process of forming of the remission. Platelets in platelet-rich-plasma (PRP) and after PRP gel-filtration through the column with Sepharose CL-2B taken from the ulnar vein of males with chronic schizophrenia during outcome from the attack of disease or in process of forming of the remission were measured. Patients were investigated on the peak of the disease attack (visit 1), at the stage of significant improvement of clinical state (visit 2), and at the stage of stable drug-induced remission (visit 3). Platelet quantities in PRP prepared by centrifugation are equal in patients in visits 1, 2 or 3. These platelets quantities are much less than similar platelet quantities in healthy individuals matched in age. The additional decreases of platelet quantities were found after the elution of PRP platelets from the column with Sepharose CL-2B. These additional platelet quantity losses are increased from visit 1 to visit 3. Such losses of cells indicate decrease in their resistance to various influences, their activation in spite of remission development in this group of patients.

[Interaction effect of serotonin transporter gene and brain-derived neurotrophic factor on the platelet serotonin content in stroke patients].

Platelet serotonin content in patients in the acute period of stroke is an important index of clinical changes during the post stroke period as well as a predictor of development of mental disorders. We studied the association between two polymorphisms (5-HTTLPR and Val66Met BDNF) and the platelet serotonin content in 47 patients with stroke. We also investigated the moderating effect of genetic variants on the association between platelet serotonin content and development of affective and anxiety disorders in stroke patients in the acute period of stroke. The interaction effect of two polymorphisms on levels of platelet serotonin was found. The lowest level was observed in patients with the diplotype LL*ValVal, the highest level--in the group of patients with the LL genotype and genotypes containing at least one copy of a Met allele. No moderating effect of genetic variants on the relationship between serotonin content and affective or anxiety disorder was found.

[Platelet peculiarities in chronic schizophrenic patients].

A comparative study of the platelet resistance to different effects was conducted in patients with chronic schizophrenia and healthy controls using column chromatography on sepharose CL-2B with the incubation at 5 degrees C during 18 h. This method allows to reveal the greater platelet activation in patients compared to the controls. The platelet number in platelet rich plasma (PRP) obtained by centrifugation was 1,8 times less in male patients with chronic schizophrenia than in the controls. This considerable decrease of platelet number in patients may be associated with the platelet deficiency in the blood stream and/or the destruction of activated platelets during blood sampling and centrifugation for the PRP preparation.

[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.

[Structure of peripheral blood platelets surface in patients with amyotrophic lateral sclerosis and multiple sclerosis].

Using scanning electronic microscopy of peripheral blood platelets in 32 patients with amyotrophic lateral sclerosis (ALS) and 6 patients with multiple sclerosis (MS), platelets activation, emerging in pseudopodiums formation, aggregation and lysis, was found. Platelets activation was more pronounced in ALS than in MS. It was most markedly seen for quantitative evaluation of the above traits. The features of platelet activation found in the study support the evidence for considering ALS as a systemic disorder being characterized by a broad spectrum of alterations of biological processes.

[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.

[The indices of the thrombocyte serotonin system and of the nerve growth factor system in children with hereditary disorders of neuropsychic development]. / Pokazateli serotoninovoi sistemy trombotsitov i sistemy faktora rosta nervov u detei s nasledstvennymi narusheniiami nervno-psikhicheskogo razvitiia.

Indices of both platelet serotoninergic system and the system of nerve growth factor (NGF) were examined in children with neurofibromatosis (15 patients), polygenic oligophrenia (24 patients) and Rett's syndrome (14 ones). There was an increase of both the level of blood serum autoantibodies (aAB) to NGF and the value of specific binding of 3H-imipramine (Bmax) in platelets of patients with oligophrenia. For this group of patients a significant negative correlation exists between the rate of platelet uptake of serotonin (Vmax value) and the degree of mental retardation (r = -0.425, p < 0.03). Decrease of both Vmax and activity of platelet NGF receptors was revealed in patients with neurofibromatosis. In such patients there was positive correlation between sensitivity of platelet NGF receptors to NGF (during their stimulation by test dose of purified NGF) and the degree of mental retardation (r = 0.697, p < 0.04). In patients with Rett's syndrome a significant increase of activity of platelet NGF receptors to NGF was observed. The conclusion was made on the existence of some general mechanism of intellectual defect development. Autoimmune processes considered to be such mechanism.

[A clinico-biological study of the thrombocyte serotonin-transport complex in therapeutically resistant patients with endogenous depression undergoing combined treatment]. / Kliniko-biologicheskoe issledovanie serotonintransportnogo kompleksa trombotsitov u terapevticheski rezistentnykh bol'nykh éndogennoi depressiei pri kompleksnom lechenii.

The platelet parameters of the functional status of the serotonin-reuptake complex were studied in drug-resistant depressive patients given various regimens of complex therapy or selective serotonin re-uptake inhibitors (fluvoxamine and fluoxetine). The most persistent and marked clinical effect was seen in electroconvulsive therapy and it was due to the normalization of the serotonin-reuptake system.

[The thrombocytic serotoninergic markers of the efficacy of electroconvulsive therapy in endogenous depressions]. / Trombotsitarnye serotoninergicheskie markery éffektivnosti élektrosudorozhnoi terapii éndogennykh depressii.

The changes of main platelet serotonergic parameters (maximal velocity of 3H-serotonin uptake, Vmax; and density of (3)3H-imipramine binding sites, Bmax) were followed up in 25 endogenously depressed patients before and after electroconvulsive therapy (ECT). It was found a marked decrease in the velocity of 3H-serotonin uptake into platelets (Vmax) from patients before ECT (especially in non-responder group) and the significant increase of Vmax- and Bmax-values after the course of ECT in responders but not in resistant patients (non-responders). The increase of Vmax- and Bmax-values in responders was evidence of the rise of the functional activity serotonin system after treatment. The results evidence about the significance of serotonergic-mechanisms in the therapeutic efficacy of ECT.

[Thrombocytic serotoninergic markers in therapy-resistant patients with endogenous depression undergoing alpha-tocopherol treatment]. / Trombotsitarnye serotoninergicheskie markery u rezistentnykh k terapii bol'nykh éndogennymi depressiiami pri lechenii al'fa-tokoferolom.

The main platelet serotoninergic parameters (maximal velosity of 3H-serotonin uptake, Vmax and density of 3H-imipramine binding sites, Bmax) were measured in 17 therapy-resistant endogenously depressed patients before and after combined treatment (antidepressants and alpha-tocopherol). It was found a significant decrease of Vmax-, Vmax/Bmax- values and the increase of Bmax- values in patients before treatment. A beneficial effect of the combined therapy was found in 47% of patients. However, it was not followed by the changes of main platelet serotoninergic parameters in patients after treatment in spite of the obtained clinical improvement. There were not also observed the significant differences of measured biochemical parameters between responders and non-responders. These findings suggest that the beneficial clinical effect of the combined antidepressive therapy with alpha-tocopherol does not involve serotoninergic mechanisms.

[The characteristics of thrombocyte morphological structure in patients with endogenous depression during antidepressant therapy]. / Osobennosti morfologicheskoi struktury trombotsitov bol'nykh éndogennymi depressiiami v protsesse terapii antidepressantami.

The study of platelets surface in patients with endogenous depressions made before the beginning of therapy, 1-3 days later and during the first days of clinical recovery with scanning electron microscopy showed that the platelets of patients who had not received antidepressants were activated. More marked activation took place after long-term therapy in the form of platelets with distinct pseudopodia, which were 2-3 times longer than cells body and with inclination to form large aggregations. This cell type is also characterized by formation of a new type of rod platelets. It is suggested that antidepressants accumulation takes place on cell membrane during long-term therapy that causes selective or general increase of membranes permeability, cytotoxicity.

[Function of the serotoninergic system of blood platelets in patients with hypertension]. / Funktsionalnoe sostoianie serotoninergicheskoi sistemy trombo- tsitov u bolnykh gipertonicheskoi bolezníu.

To investigate if there can be alterations in the 5-hydroxytryptamine (5-HT) uptake system in the sensitivity of platelets in patients with essential hypertension, 38 hypertensive patients and 37 normotensive healthy subjects were compared. In patients, the maximal 5-HT uptake velocity was reduced. The density of binding sites for 3H-imipramine was elevated in hypertensive females, but unchanged in males. The sensitivity of 5-HT uptake to trazodone was unchanged in patients. Half-maximal concentrations of 5-HT for inducing a shape change reaction of platelets were positively correlated with diastolic blood pressure in male patients and were reduced in female mild hypertensives. It is suggested that these changes are likely to be involved in the pathogenesis of hypertension.

[The effect of different methods of isolating thrombocytes on the surface structure and biochemical parameters of the serotonin system of these cells]. / Vliianie raznykh sposobov vydeleniia trombotsitov na poverkhnostnuiu strukturu i biokhimicheskie parametry serotoninovoi sistemy étikh kletok.

The method of platelets' isolation influences their morphofunctional state. The study of the surface structure of platelets with the method of scanning electron microscopy shows, that the nonactivated form of platelets is characterized for the cells, isolated by gel filtration, but platelets which are isolated by centrifugation are activated. Platelets' activation under centrifugation is shown to connect with the changes of biochemical parameters of platelet serotonin system: the increase of the velocity of the 3H-serotonin reuptake and of the 3H-imipramine specific binding.

Does platelet serotonin receptor supersensitivity accompany endogenous depression?

In a population of drug-free bipolar and unipolar depressed women, it was found that the concentration of serotonin sufficient to induce half-maximal shape change velocity in platelets is significantly (p less than 0.001) lower (0.13 +/- 0.0.04 microM) than that of closely matched controls (0.532 +/- 0.1 microM). This platelet concentration becomes higher after 1-3 months of antidepressant treatment (0.47 +/- 0.16 microM). Possible mechanisms for this up- or down-regulation of platelet serotonin receptor responsiveness are discussed.

[Activity of platelet serotonin receptors of patients with endogenous depression before and after treatment with antidepressive agents]. / Aktivnost' serotoninovykh retseptorov na trombotsitakh bol'nykh éndogennymi depressiami do i posle lecheniia antidepressantami.

Effective 5-HT concentration eliciting the half-maximal rate of platelet deformation (aggregation) in drug-free bipolar or unipolar depressed women was significantly (p less than 0.001) lower as compared with matched controls (0.13 +/- 0.04 microM and 0.532 +/- 0.1 microM, respectively). After 1-3 months of antidepressant treatment this value increased to 0.47 +/- 0.16 microM and was no longer different from control. Possible mechanisms controlling the activity of serotonin2 platelet receptors are discussed.

[Sensitivity of the retrograde uptake of H3-serotonin to imipramine and trazodone in patients with endogenous depression treated with antidepressive drugs]. / Chuvstvetel'nost' obratnogo zakhvata 3H-serotonina k imipraminu i trazodonu u bol'nykh endogennymi depressiiami pri lechenii antidepressantami.

The potency of imipramine (IMI) and trazodone (TRA) to inhibit (3H)-serotonin intake in unipolar and bipolar endogenous depressed patients (women aged 17 to 57 years) was evaluated before and during the antidepressant treatment. The potency of IMI was lower and that of TRA higher in patients as compared to controls. The both drugs' potencies became normal in patients treated with antidepressants. The significant decrease of imipramine binding sites density (Bmax) was evident after the treatment as against the normal levels. Significant correlation was observed between a severity of the patient's state evaluated using Hamiltone depression rating scale and the TRA potency but not IMI potency or Bmax. The data suggest different mechanisms regulating the serotonin uptake sensitivity to IMI and TRA. These are apparently involved in the pathogenesis of endogenous depression.

[Development of subsensitivity to imipramine in the system of reverse serotonin uptake by thrombocytes in patients with endogenous depression]. / Razvitie subchuvstvitel'nosti k imipraminu sistemy obratnogo zakhvata serotonina na trombotsitakh bol'nykh endogennymi depressiami.

The inhibitory effect of imipramine (IC50) on [3H]serotonin uptake and its kinetic parameter (V400) were measured in platelets of 9 patients with unipolar and 6 with bipolar affective disorder. The IC50 and V400 values in depressed patients were significantly higher (p less than 0.002) than these found in the control group. Treatment with antidepressants significantly decreased the IC50 values. The results support the hypothesis postulating that depression is related to a decreased modulatory capacity of imipramine binding sites and that the clinical effectiveness of these drugs is associated with the said modulatory capacity.