[Low doses of quetiapine (Seroquel) as an impulsivity corrector in patients with bipolar affective disorder in remission]. / Nizkie dozy kvetiapina (Serokvelya) v kachestve korrektora impul'sivnosti u patsientov s bipolyarnym affektivnym rasstroistvom v remissii.

OBJECTIVE: To evaluate the effectiveness of low doses (25-75 mg/day) of quetiapine (Seroquel) in patients with bipolar affective disorders in a euthymic state with signs of impaired impulse control. MATERIAL AND METHODS: The main criteria for patients' selection were as follows: both sex, diagnoses of bipolar affective disorders, remission (euthymic state), adult age (from 18 to 60 years old), stable basic therapy. The duration of the study was 6 weeks, a dose of quetiapine (Seroquel) varied from 25 to 75 mg. The examinations were carried out with the Barratt scale, computerized Go-No-Go and Balloon tests. RESULTS: The study group included 32 patients (11 men and 21 women), mean age 31.2±9.7 years (minimum 18, maximum 60 years). The changes in Barratt total score (p=0.000014, Wilcoxon test, effect size 0.48) and Balloon total earnings (p=0.03, Wilcoxon test, effect size 0.22) were statistically significant and reflected clinically significant improvement. The changes of the indices of the Go-No-Go test were not significant. The data of fMRI showed an increase in the connectivity of the cortex of the central and parietal tegmentum of the left hemisphere with other areas of the brain, which correlated with the changes in psychometric and test parameters. CONCLUSION: The results of the study showed that add-on of the low doses of quetiapine (Seroquel) significantly decreases impaired impulse control in remitted patients with bipolar affective disorders both in self-evaluation and in risk-taking experimental test. The drop of high level of impulsivity can improve the quality and stability of remission and reduce behavioral risks due to impaired impulse control.

[An effect of cholinesterase blockade on negative symptoms in schizophrenia]. / Vliyanie blokady kholinesterazy na negativnye rasstroistva pri shizofrenii.

Abstruct. OBJECTIVE: To assess the possibilities of influencing the severity of negative disorders in schizophrenic patients with cholinesterase blockade. MATERIAL AND METHODS: The study included stable 26 patients (13 of them women), average age 40.4 (SD 11.7) with paranoid schizophrenia, episodic form according to ICD-10). All patients received antipsychotic therapy, which was not changed at least for 2 months. We used psychometric scales (Positive and Negative Syndrome Assessment Scale (PANSS), Global Functioning Scale (GAF), neurocognitive techniques (Brief Assessment of Cognition in Schizophrenia-BACS), projective psychological techniques (Rorschach test). RESULTS AND CONCLUSION: The results of the study showed that augmentation of maintenance antipsychotic therapy with a cholinesterase blocker (ipidacrine at a dose of 20 mg per day) had positive impact on negative symptoms, decreasing the severity of emotional deficiency. The positive changes of cognitive impairment, measured with BACS, occurred regardless of changes in the severity of negative disorders, measured with PANSS. The Rorschach test showed an improvement in the conventional orientation of the patients' thinking. No exacerbation of psychotic symptoms was registered.

[The use of acatinol in the treatment of stable patients with schizophrenia with predominance of behaviour disorganization and subcatatonic features].

Our study was based on the hypothesis that a non competitive antagonist of NMDA receptors can improve clinical effects of antipsychotic therapy in a subgroup of patients with schizophrenia with clinical signs of glutamatergic hyperfunction such as catatonic symptoms and disorganization. The study design was open and non-comparative. The duration of the study for each patient was 6 months, the target dosage of acatinol was 20 mg. Forty stable patients with schizophrenia with predominance of signs of disorganization and subcatatonic symptoms were included. The following instruments were used: PANSS, NSA, CGI, BACS, UKU. Adding of acatinol to the antipsychotic treatment improved clinical symptoms, cognitive functioning and social functioning and decreased the number of side effects. The drug was well-tolerated.

[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.

[Effects of the anticholinesterase drug neuromidin in patients with schizophrenia with marked neurocognitive deficits].

An objective of the study was to investigate the effectiveness of neuromidin in stable schizophrenic patients with predominance of symptoms of pseudoorganic deficits. Fifty-five patients stable after a transition from routine medication to monotherapy with risperidone were randomized into two groups with add-on placebo or neuromidin treatment. Patients were studied during 24 weeks. The PANSS and a battery of neurocognitive tests were used for assessment of treatment. In the end of the trial, positive changes on the following PANSS items - N1, N2, N6, N7, G4, G7 and G13 were observed in the neuromidin group. In the placebo group, the changes were found only on one PANSS item - N2. The decrease of scores on this item (emotional withdrawal) during the study was more significant only in the patients receiving neuromidin (p=0,037). The results of assessment of cognitive functioning showed the positive changes in visual-spatial memory, attention, retention and retrieval of data, planning in the group treated with neuromidin. In the placebo group, the positive changes were observed only in one index - one type of mistakes (omissions) in visual-spatial memory test. In the end of the trial, between-group differences were significant for planning - number of tasks with time-limit violation and rule violations. All differences were beneficial for patients treated with neuromidin. Not all tests were sensitive to changes in cognitive status of patients: indices of working memory, psychomotor speed, flexibility of attention were not changed significantly in both groups, nor they changed between groups. The authors conclude that the problem of rationality of add-on anticholinergic treatment in schizophrenia is not solved yet due to the difficulties in selection of patients and tests for cognitive assessment. The need of further studies is emphasized.

[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.

The state of the serotonin transporter protein in the platelets of patients with somatoform [correction of somatiform] disorders.

The role of the serotonin transporter protein (STP) in the development of somatoform [corrected] disorders was addressed in a correlational study of the levels of immunoreactive STP (IR-STP) using site-specific antibodies against the least conserved (among a group of other cotransporters) epitope at the C-terminal of STP and the level of anxiety symptoms in patients with somatoform [corrected] disorders. A total of 22 patients were studied, with DSM-IV diagnoses of somatoform [corrected] disorders, along with 32 mentally healthy subjects of comparable age and sex. Immunoblotting of IR-STP from patients from healthy donors produced a diffuse band between 68 and 105 kDal and a clear narrow band at 43 kDal. The 43-kDal IR-STP protein was almost completely absent from most patients, as compared with the levels of this protein in healthy donors. This result suggests an abnormality of STP processing or, perhaps, alternative splicing of the gene encoding STP in patients with somatoform [corrected] disorders, and this appears to reflect the dysfunction in serotoninergic transmission in the CNS in these patients.

[The experience of application of olanzapine: an atypical neuroleptic in acute schizophrenia]. / Opyt primeneniia atipichnogo neiroleptika -- olazapina v ostrom periode shizofrenii.

Thirty adult patients with acute schizophrenia were included into six-week open-labelled, non-comparative trial of olanzapine with free dosing from 5 to 20 mg per day. For assessment of efficacy and safety of the treatment PANSS, BPRS, CGL and ESRS scales were used. The main criterion of improvement was the percentage of reduction of BPRS score to the end of the trial. More than 50% reduction was achieved in 23% of the patients, more than 20%--in 57% of the cases; 20% were non-responders (reduction less than 20%). Changes in the scores of the positive and negative PANSS subscales were significant (p < 0.001) starting from the second week of treatment. There was no correlation in changes in positive and negative scores as well as in changes in negative and ESRS scores. The first signs of the antipsychotic effect (a reduction of tension, suspiciousness and fear) appeared just in the first two weeks of treatment and manifested in the reduction of delusions and hallucinations. Reduction of depression didn't correlate with changes in scores of the positive or negative PANSS subscales. The changes in behavioral and cognitive symptoms were statistically significant starting from the second week of treatment. No clinically significant signs of extrapiramidal syndrome or other side-effects except weight gain were observed during the trial.

[The status of serotonin protein -- a serotonin transporter in thrombocytes in patients with somatoform disorders]. / Sostoiane belka -- perenoschika serotonina v trombotsitakh u bol'nykh s somatoformnymi zabolevaniiami.

The role of serotonin transporter (SERT) protein in the development of somatoform disorders (SD) was investigated. An association study was performed in terms of the evaluation of the level of SERT immunoreactive (IR-SERT) protein using site-specific antibodies directed at SERT C-terminus fragment, poorly conserved among the other cotransporters. The level of the anxious symptomatology was also estimated in the patients with SD. 22 patients, who met DSM-IV criteria for somatoform disorders, and 32 normals were examined. In platelets from normals, IR-SERT protein migrated as a difuse band between 68 and 105 kDa, and a major sharper band at 43 kDa. Almost complete disappearance of platelet 43 kDa IR-SERT protein band was observed in most of the patients with SD. These findings permitted to suggest a possibility of either biosynthetic or processing abnormality of SERTs in the affected population, that might reflect a dysfunction of serotonin neurotransmission in CNS of the patients with SD.