[A differential approach to the improvement of prevention and correction of neuroleptic side extrapyramidal disorders with pantogam activ in patients with schizophrenia]. / Differentsirovannyi podkhod k usovershenstvovaniyu metodov preduprezhdeniya i korrektsii neirolepticheskikh pobochnykh ekstrapiramidnykh rasstroistv preparatom pantogam aktiv u bol'nykh shizofreniei.

AIM: To assess the efficacy and safety of pantogam active (PA) in prevention and correction of neurological side-effects during the course neuroleptic treatment of acute endogenous psychoses. MATERIAL AND METHODS: Eighty schizophrenic patients (mean age 33 years) with acute psychosis were examined. All patients received 28-day course treatment with typical and atypical neuroleptics. Two equal groups were studied: patients of the first group were treated with trihexyphenidyl (THP) in dose of 0,002-0,012 mg and patients of the second group received in addition PA in dose 0,9 mg/day. Clinical-observation, psychometric scales (PANSS, CGI-S, UKU) were administered at baseline and in 1st,3rd,7th, 14th, 21st, 28st day. RESULTS: PA in the combination with THP improved tolerability to neuroleptic therapy in whole and exerted the better correction effect on neuroleptic extrapyramidal disorders (EPD) compared to THP monotherapy. The number of patients with ERD was reduced by 1.5 times and prevention of EPD was observed 3 times more frequent in the group treated with PA. In the THP group, other adverse effects (AE) were 1,7 times more frequent and the total AE score was 2,5 times greater compared to the PA group (131 vs 50). Correction and preventive effects of the combined treatment on the clinically severe symptoms of EPD (akathisia, muscle dystonia) were more frequent in patients treated with typical neuroleptics. A less amount of THP (by 1,2 times) was used to stop EPD in the PA group. CONCLUSION: PA in the combination with THP has demonstrated the clear neuroprotective effect on the development, frequency and clinical presentations of neurological side-effects. The РА can be recommended as a drug of choice for correction and prevention of neuroleptic side-effects, it promotes their tolerability and improves quality of life during the course treatment.

[Impairments of Neurocognitive Mechanisms of Decision-Making in Depression.]

A multidisciplinary clinical-psychological-neurophysiological study has been performed in 28 depressive patients (females, aged 18-56) and 50 healthy volunteers (females, aged 18-55) in order to analyze the relationships between the impairments of neurocognitive mechanisms of decision-making based on logics and considerations or on emotional experience (emotional learning) in uncertain situation and clinical and neurophysiological signs of depression. The severity of depression was assessed quantitatively using Hamilton's Depression Rating Scale (HDRS-17). Tests "10 words", Wisconsin Card Sorting Test (WCST), and Iowa Gambling Task (IGT) were used for quantitative assessment of cognitive functions. Multichannel resting EEG was recorded in all depressive patients in order to assess the brain functional state. Neurocognitive deficit was observed in all the patients; its pronounce correlated positively with the severity of depression. The ability to make decisions based on both logic and considerations (in WCST), which is associated with EEG signs of hypofrontality, and on emotional learning (in IGT) was impaired. Only in depressive patients reduced ability to make rational decisions based on logics and considerations resulttd in a compensatory shift towards decision-making based on emotions, which led to relatively higher results of emotional learning. The data suggests that hypofrontality causes difficulties in making decisions that requires logical reasoning and the disinhibition of subcortical (including hippocampal) brain structures, the activation of which provides better results of emotional learning.

[Transcranial Magnetic Stimulation in the Combined Treatment of Pharmacoresistant Depression: Dynamics of Clinical, Psychological and EEG Parameters].

In order to investigate the mechanisms of the therapeutic effect of transcranial magnetic stimulation (TMS) of the left dorsolateral prefrontal cortex in patients with depression, we studied the dynamics of clinical parameters, a number of cognitive functions, and the spectral structure of resting EEG in 20 patients with pharmacoresistant depression in the course of combined treatment including TMS. It was shown that short course (10 sessions) of TMS significantly enhanced and accelerated the effect of antidepressants. The course of TMS contributed not only to the reduction of depressive symptoms but also to the improvement of general condition and the recovery of some impaired cognitive functions. The therapeutic effect of TMS seems to be provided by the activation of not only the prefrontal cortex itself but also of some subcortical structures closely linked with it. Thus, TMS appears to be a promising non-drug method for the treatment of clinical conditions and for the correction of brain functional state in patients with depression, including the use in combined treatment of depressive disorders in cases of pharmacoresistance.

[Clinical and pathopsychological aspects of forming negative disorders in remissions of shift-like schizophrenia treated with different generations of neuroleptics]. / Klinicheskie i patopsikhologicheskie aspekty formirovaniya negativnykh lichnostnykh izmenenii v remissii pri pristupoobraznoi shizofrenii pri lechenii neiroleptikami raznykh pokolenii.

OBJECTIVE: To determine clinical and pathopsychological parameters of negative personality changes, their diagnostic and predictive significance based on the variant of neuroleptic treatment in the dynamics of remissions in shift-like schizophrenia. MATERIAL AND METHODS: Twenty-nine female patients diagnosed with ICD-10 schizophrenia (items F20.01 and F20.02) were examined. The patients were treated with typical neuroleptics (TN) or atypical (ATN) neuroleptics in the hospital and then as outpatients. Patient's state was assessed clinically and psychometrically with the PANSS at admission, at the beginning of remission and after one and two years of remission. Mean score of positive (PS) and negative (NS) symptoms was determined differentially in the dynamics basing on the neuroleptic used. Twenty-seven patients underwent experimental/pathopsychological examination. RESULTS AND CONCLUSION: In different stages of the dynamics of shift-like schizophrenia, NS had different capacity of «reversibility¼ and were distinctly associated with the illness-shaping influence of PS severity and activity and characteristics of psychotropic effect of the neuroleptics. The highest severity of NS was noted in the stage of active psychosis (up to 3.6 and 4.2 scores), with the following decrease in the beginning of remission (up to 2.3 and 2.8 scores). The most distinct trend towards the reduction of NS in the first and second years of remission (up to 2.0-1.0 scores), along with a trend to the complete reduction of PS, was identified in patients treated with ATN. In patients treated with TN, the severity of NS was relatively stable in all stages of remission, with a trend towards the increased severity (up to 2.8 and 3.2 scores) with the stable reduction of PS to1.6 scores. The distinct property of ATN to exert the reducing psychotropic effect on NS and the lack of antinegative effect in the antipsychotic spectrum of TN is discussed.

[Clinical-genetic parameters and the nosological evaluation of schizoaffective psychosis in systematics of attack-like endogenous psychoses].

Authors studied 1013 first- and second degree relatives in families of 193 probands. The probands were stratified by clinical diagnosis into 6 groups: 1) nuclear variant of schizoaffective psychosis (SAP); 2) "marginal" (intermediate) variant of SAP; 3) schizoaffective variant of schizophrenia; 4) recurrent schizophrenia; 5) attack-like progressive schizophrenia; 6) bipolar affective disorder or manic-depressive psychosis (MDP). Probands (n=109) and their relatives were studied using the direct clinical examination; the study of 84 probands and their relatives was based on the medical records from the genetic archive of Mental Health Research Center, Russian Academy of Medical Sciences. Mental pathology was found in 72,5% of relatives; 27,5% were healthy. Prevalence of endogenous and non-endogenous psychoses, personality disorders and cases of alcoholism and suicides in the families of probands was studied. A "set" of these psychopathologies was similar in families of all probands and their frequency was higher than that in the general population that confirmed the affiliation of SAP with endogenous diseases by genetic characteristics. In patients with SAP, hereditary characteristics differed by the frequency, correlation and preference of some types of mental pathology compared to families of patients with schizophrenia and MDP, in particular, hereditary characteristics of patients with recurrent schizophrenia and MDP which were identified with SAP by many authors. The clinical-genetic patterns revealed in the study are considered as an argument for nosological independence of SAP.

[Molecular-genetic approach to the clinical and nosologic differentiation of schizoaffective disorder].

The aim of the study was to find molecular-genetic variants associated with nosologically independent schizoaffective disorder (SAD) which clinical presentations had been specified earlier. Authors studied a sample of 230 patients including 39 with "nuclear" (nosologically independent) and marginal (intermediate) variants of SAD, 53 with schizophrenia with schizoaffective states and 81 with schizophrenia with affective disorders in the structure of psychotic attacks. In these groups, authors studied the following polymorphisms: 5-HTTLPR, Val66Met BDNF, T102C 5-HTR2a and С677Т MTHFR. Frequencies of genotypes were compared to those in a sample of healthy controls (328 people). It has been shown that the "nuclear" variant has a genetic profile represented by a combination of genetic variants (SS*ValVal*TT*CC) that distinguishes this clinical entity from other groups and controls. The results may be used as an additional criteria for clinical and nosological differentiation of SAD from schizophrenia.

[Schizoaffective psychosis: nosological evaluation and differential diagnosis].

Basing on the peculiarities of psychopathological presentations and dynamics of disease in 253 patients with an ICD-10 diagnosis of schizoaffective disorder (F25), the authors argue for the diagnostic validity of this disease. Schizoaffective psychosis (SAP) is considered in the context of endoform schizophrenic reaction in people with schizotypal personality with signs of reactive lability. In the dynamics of a schizoaffective episode, this reaction is formed in the period, but not in the structure, of endogenous phasic affective disorders and emerges itself as psychotic symptoms characteristic of schizophrenia which are independent from circulatory affective symptoms pathogenetically and pathokinetically. The clinical peculiarity and specifics of clinical-psychopathological presentations of SAP as a diagnostically valid entity are discussed. Diagnostic criteria of its differentiation from affective disorders and schizoaffective variants of episodic and recurrent schizophrenia are presented.

[Clinical and nosological approach to diagnosis of schizoaffective psychosis]. / Kliniko-nozologicheskii podkhod k diagnostike shizoaffektivnogo psikhoza.

Using clinical and psychopathological method, 134 patients who met the ICD-10 criteria of diagnosis of schizoaffective psychosis (F25), were examined. Relatively small prognostic informative value of standard schizoaffective psychosis differentiation into affective- and schizo-dominant types was found. Subtyping of schizoaffective psychosis according to peculiarities of delusion formation in the picture of the disease attacks proved to be more significant. Given clinico-psychopathological features of circular affective and delusional disorders and their pathokinesis, as well as dynamics types and disease outcome, a schizoaffective psychosis systematization has been elaborated. That includes 3 nosologic types: "nuclear" type with non-progressive phase dynamics; "marginal" (intermediate) type and schizoaffective type of attack-like progressive schizophrenia. The concept of nosologic independence of schizoaffective psychosis ("nuclear" type) is discussed.

[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.

[Typological characteristics of manifest states of schizo-dominant form of schizoaffective psychosis]. / Tipologicheskaia kharakteristika manifestnykh sostoianii shizodominantnoi formy shizoaffektivnogo psikhoza.

On the basis of a clinical and psychopathological analysis of 77 patients with schizodominant form of schizoaffective psychosis their typological division is suggested according to predominant mechanism of delusion formation. Two types are described: 1) with formation of an acute sensitive delusion; 2) with predominance of acute interpretative delusion. It was established the interrelationship of a psychopathologic structure of the delusional disturbances with the special features of affective disorders in their formation and development in the structure of manifest schizodominant states. Clinical heterogeneity of these disturbances and their differentiation accounting for different characteristics of delusion formation is discussed. The conclusion is also made about the necessity of a further comparison of the described types with both the course and prognosis of the disease.