[Augmentation therapy of resistant schizophrenia with rhythmic transcranial magnetic stimulation]. / Augmentatsiya terapii rezistentnoi shizofrenii metodom ritmicheskoi transkranial'noi magnitnoi stimulyatsii.

OBJECTIVE: To identify the clinical efficacy of rhythmic transcranial magnetic stimulation (rTMS) in resistant schizophrenia. MATERIAL AND METHODS: The study included 44 male patients with resistant schizophrenia, divided into 4 groups: with depressive (group 1; n=11, 25.0%), with hallucinatory (group 2; n=12, 27.3%), with negative (group 3; n=11, 25.0%) and with delusional symptoms (group 4; n=10, 22.7%). Patients received rTMS, the parameters of which were determined depending on the typological variety, for 3 weeks (15 sessions). Psychometric assessment was carried with PANSS, CGI-S, CGI-I, SANS, CDSS, AHRS when included in the study (0 day), after stimulation (21 days) and by the end of the study (42 day) that allowed evaluation of both the severity of the therapeutic effect and its duration. RESULTS: By the end of the course of stimulation, patients of the first three groups developed a distinct positive effect corresponding to a significant reduction in the total PANSS score: group 1 - 24.4% (p=0.002), group 2 - 8.3% (p=0.02), group 3 - 11.7% (p=0.001), which remained stable by day 42 in patients of the first (p=0.001) and second (p=0.005) groups. In patients with delusional symptoms (group 4), a subpsychotic state developed with a corresponding increase in the total PANSS score by 9.7% (p=0.007) requiring a course of relief therapy, which showed effectiveness by the end of the observation (day 42), indicating that resistance was overcome. CONCLUSION: The study demonstrated the validity of rTMS as an adjuvant method of treatment in the resistant schizophrenia. To implement the potential of rTMS, it is necessary first of all to take into account the structural features of the condition, as well as to continue improving the stimulation technique itself (increasing the duration of the course, developing supportive courses).

Thermal Balance of the Brain and Markers of Inflammatory Response in Patients with Schizophrenia.

In patients with schizophrenia, the thermal balance of the cerebral cortex was studied by means of microwave radiothermometry method and compared with the markers of systemic inflammation and clinical features of the disease course during therapy. Low temperature heterogeneity of the cerebral cortex was associated with an increase in the activity of inflammatory markers in the blood and, in most cases, with a positive response to therapy. High temperature heterogeneity of the cerebral cortex was typical of patients with insufficient activity of the inflammatory proteolytic system, high levels of antibodies to brain antigens, a more severe course of the disease and, in most cases, with resistance to therapy. A conclusion was made about the diagnostic value of the study of the thermal balance of the brain in patients with schizophrenia.

[The course of postpsychotic depressions in adolescence]. / Dinamika postpsikhoticheskikh depressii v yunosheskom vozraste.

OBJECTIVE: To identify psychopathological features of postpsychotic depressions formed within the achievement of remission after the first psychotic episode in adolescence. MATERIAL AND METHODS: Fifty-six male patients of adolescent age (average age 19.7±2.5 years) with postpsychotic depression (F20, F25) were enrolled. The study used clinical-psychopathological, psychometric and statistical methods. HDRS-21 was used for psychometric assessment of depressive symptoms, and suicidal risk was assessed using SSI. RESULTS: There were two types of post-psychotic depression: type 1 with a positive affectivity (58.93%, n=33) and type 2 with negative affectivity (41.07%, n=23). Significant differences in the structure of the first psychosis were found (χ2=7.8; p=0.02). In the case of depression type 1, the HDRS-21 score was 17.49±7.49 points with the largest number of points on the sub-scales «low mood¼ (2.81±0.83) and «mental anxiety¼ (2.88±0.45). The SSI average score was 7.81±6.46. Anti-vital thinking was noted by 75.76% (n=25). In the case of depression type 2, the HDRS-21 average score was 23.68±9.24 points (the largest number of points was fixed in the sub-scales «low mood¼ - 2.44±0.73, «work and activity¼ - 3.19±0.89). The SSI average score was 12.30±8.47. CONCLUSION: The study showed the heterogeneity of the course of postpsychotic depressions that occur after a manifest psychotic episode of adolescence. Differences in the structure of depression were identified, which are important for therapeutic tactics and prognosis of the disease.

[Immunological and clinical aspects of the long-term stages of youth schizophrenia]. / Immunologicheskie i klinicheskie aspekty otdalennykh etapov yunosheskoi shizofrenii.

OBJECTIVE: To study the spectrum of inflammatory markers and their association with the psychopathological symptoms in patients with youth schizophrenia in the long-term follow-up study. MATERIAL AND METHODS: Thirty-four male patients with schizophrenia (ICD-10 F20) first manifested at the age of 16-25 years were followed-up for 20-25 years (mean duration 22±2.9 years). The mean age of patients at the time of follow-up examination was 46.7±3.2 years. PANSS and PSP scales were used to quantify the severity of psychopathological symptoms. The control group consisted of 20 mentally and somatically healthy people matched for age with the patient group. The immunological parameters (the activity of the neutrophil protease of leukocyte elastase (LE) and its endogenous inhibitor α1-PI, as well as the level of antibodies to S100B and basic myelin protein) included in the medical technology «Neuroimmunotest¼ were determined in blood plasma. RESULTS: Three types of follow-up outcomes of youth schizophrenia were found: the first type - with a predominance of personality dynamics (n=10); the second type - with actual negative disorders (n=9), the third type - with relevant positive and negative disorders (n=15). All patients showed a significant increase in the activity of LE (227.9 nmol/min ml) and α1-PI (45.8 IU/ml) compared with the controls. There were a significant increase in LE and α1-PI in patients of the first type (245 nmol/min ml and 46.4 IU/ml), a significant increase in α1-PI in patients of the second type (42.0 IE/ml) compared with the controls and the absence of significant differences with the controls in LE and α1-PI in patients of the third type (226.8 nmol/min ml and 49.6 IE/ml). These differences reveal the immunological heterogeneity of the types that makes it possible to identify immunological groups of patients, differing in the level of activation of inflammation. CONCLUSION: Residual psychopathological symptoms observed in the late stages of schizophrenia can be determined by both low/moderate inflammation and genetic mechanisms (in patients with damped inflammation or depletion of the inflammatory potential).

[Therapeutic drug monitoring of aripiprazole as part of the individualization of the pharmacotherapy of schizophrenia]. / Provedenie terapevticheskogo lekarstvennogo monitoringa aripiprazola v ramkakh individualizatsii farmakoterapii shizofrenii.

OBJECTIVE: To personalize pharmacotherapy with aripiprazole in patients with schizophrenia via therapeutic drug monitoring (TDM). MATERIAL AND METHODS: TDM of aripiprazole (ARI) and its active metabolite dehydroaripiprazole (DHA) was performed for patients diagnosed with schizophrenia (ICD-10 F20.00; F20.01; F20.02). Thirty-six parameters were assessed. To carry out TDM, the method of high-performance liquid chromatography with mass spectrometry was chosen employing a validated method. RESULTS: TLM was performed in a group of young patients: 26.5±10.1 years old, average weight 77.2±16.2 kg, average PANSS score 81.4±21.4, UKU score 14.5±3.9. An average ARI concentration was 18.4±7.9 mg, serum ARI concentration 417.9±362.4 ng/ml, serum DHA concentration 117.5±116.1 ng/ml and the total concentration 535.4±478.5 ng/ml. Equations of correlation dependences of concentration on dose are obtained for ARI and DHA. CONCLUSION: The results show the significant metabolism of ARI. A combined determination of the main substance and its active metabolite DHA in the patient's blood serum is advisable for correct assessment of the TLM result in patients with mental diseases.

[Rhythmic transcranial magnetic stimulation in the treatment of resistant depression in schizophrenia]. / Ritmicheskaya transkranial'naya magnitnaya stimulyatsiya v terapii rezistentnykh depressii pri shizofrenii.

Rhythmic transcranial magnetic stimulation (rTMS) has long been actively used in the treatment of depressive disorders in various mental illnesses. At the same time, the question of the predictability of the results of this method for an individual patient remains open. Based on the existing ideas about the relationship of rTMS mechanisms with changes in the state of neural networks, one of the most perspective line is the search for prognostically significant neurophysiological markers. The study analyzed a wide range of EEG characteristics and evoked potentials recorded before treatment in the groups of responders and nonresponders in patients with depressive symptoms in schizophrenia, who have completed a course of rhythmic transcranial magnetic stimulation. The study revealed associations between an unfavorable treatment outcome and greater coherence in the alpha range (mainly in the caudal regions bilaterally) and less coherence in the beta1 range (involving temporal leads and left-hemisphere asymmetry). At the same time, such indicators as the amplitude of the N100 wave and the negativity of the mismatch were uninformative in terms of predicting the effectiveness of therapy.

[Immune-inflammatory markers in remission after a first-episode psychosis in young patients]. / Immunovospalitel'nye markery stanovleniya remissii posle pervogo psikhoticheskogo pristupa v yunosheskom vozraste.

OBJECTIVE: To study clinical, psychopathological and immunological features of remission after first-episode psychosis in young patients to determine the patterns of this stage and the possibility of using the results for monitoring, prognosis and optimization of therapy. MATERIAL AND METHODS: Fifty patients, aged 15-25 years, mean age 20.8±2.2 years, experiencing first-episode psychosis (F20, F25) and 45 healthy age-matched young men (mean age 19.2±3.2 years) were examined. The average age of psychosis manifestation was 19.8±2.5 months. Clinical, psychopathological, psychometric (PANSS and HDRS) and immunological («Neuro-immuno-test¼ technology) examinations were carried out at the psychotic state, during period of psychopathological symptoms reduction and further for 1-2 years until complete/significant reduction of psychotic symptoms. RESULTS: Three stages of remission are revealed: I - the stage of reduction and modification of leading psychotic symptoms, II - the stage of stabilization of mental functions, III - the stage of reintegration of mental functions. It has been shown that each stage corresponds to different features of clinical symptoms and also certain spectra of immune markers (activity of leukocyte elastase, α1-proteinase inhibitor and level of autoantibodies to S100-B and OBM proteins) in blood serum of patients. The differences in the spectra of immune parameters at the second stage of remission in patients with affective (depressive) disorders define various patterns of post-psychotic development of disease. The most representative are immunological features of the third stage of remission. CONCLUSION: The dynamics of immune markers in the course of remission can be considered as a biological criterion for assessment of the outcome of the first first-episode psychosis and the completeness of remission.

[Executive control of language production in schizophrenia: a pilot neuropsychological study]. / Proizvol'naya regulyatsiya produktsii rechi pri shizofrenii: pilotnoe neiropsikhologicheskoe issledovanie.

OBJECTIVE: To test the general hypothesis about executive deficits in language production in schizophrenia as well as more specific hypothesis that this deficit would be more pronounced in the case of higher demand on executive functions. MATERIAL AND METHODS: Twenty-five patients with schizophrenia and twenty-seven healthy controls were asked to tell a story based on a series of pictures and then to give an oral composition on the given topic. RESULTS AND CONCLUSION: Schizophrenia patients, compared to controls, demonstrated poorer programming as well as shorter text and phrase length in both tasks. Oral composition on the given topic in patients was characterized by the presence of agrammatism, need for leading questions due to the difficulties of story plot generation as well as higher variance in syntactic complexity and text length. Therefore, the authors revealed executive deficit in language production, more pronounced in the task with less numerous external cues for planning and sequential text explication, in schizophrenia patients.

[Neuroanatomical brain profile of juvenile shiftlike schizophrenia: morphometry of grey matter in the prefrontal cortex and subcortical structures]. / Neiroanatomicheskie osobennosti golovnogo mozga pri iunosheskoi pristupoobraznoi shizofrenii: morfometriia serogo veshchestva prefrontal'noi kory i podkorkovykh struktur.

AIM: To determine neuroanatomical peculiarities of grey matter in some regions of the prefrontal cortex and several subcortical structures in patients with juvenile shift like schizophrenia (F20 ICD-10). MATERIAL AND METHODS: Forty-three young male patients and 54 mentally healthy men without family history of mental diseases underwent structural MRI with T1 high resolution images. RESULTS: As compared to mentally healthy subjects, there was a decrease of grey matter thickness in all tested regions of the prefrontal cortex in patients. No between-group differences in subcortical structures volumes were found. No correlations between structural changes and psychopathological symptoms were observed. CONCLUSION: Structural abnormalities of the frontal lobes in juvenile shift like schizophrenia are not associated with severity of psychopathological symptoms.

[Genetic variations associated with premorbid personality in patients with schizophrenia]. / Geneticheskie polimorfizmy, assotsiirovannye s razlichnoi stepen'iu vyrazhennosti premorbidnykh lichnostnykh anomalii u bol'nykh shizofreniei.

AIM: To search for genetic variants associated with premorbid personality in patients with schizophrenia. MATERIAL AND METHODS: The sample included 272 men diagnosed with schizophrenia or schizoaffective disorder. Patients were divided into 3 groups based on premorbid personality difficulties: mild (group 1, n=110), moderate (group 2, n=113), marked (group 3, n=49). The following polymorphisms were genotyped: 5-HTR2A (T102C), 5-HTTLPR, BDNF (Val66Met), CRP (-717A>G). RESULTS: A significant increase in the frequency of the CC (5-HTR2A T102C), LL (5-HTTLPR) and Met/Met (BDNF Val66Met) genotypes was identified in group 3 compared to group 1. Frequencies of CC and LL genotypes were significantly higher in group 2 compared to group 1 as well. The differences between group 2 and group 3 were found only for the Met/Met genotype. There were no between-group differences in the frequencies of CRP (-717A>G) genotypes. CONCLUSION: 5-HTR2A (T102C), 5-HTTLPR, BDNF (Val66Met) polymorphisms previously reported to modify schizophrenia course are also associated with premorbid personality in schizophrenic patients.

[Clinical-psychopathological aspects of therapeutic effects of agomelatine (valdoxan) and its place in perfection of methods of therapy of postschizophrenic depressive disorders]. / Kliniko-psikhopatologicheskie aspekty osobennostei terapevticheskogo deistviia agomelatina (val'doksana) i ego mesto v usovershenstvovanii metodov terapii postshizofrenicheskikh depressii.

AIM: To determine a therapeutic effect of agomelatine (valdoxan) on post-schizophrenic depression (PSD), taking into account its psychopathological structure. MATERIAL AND METHODS: A total of 33 patients of both sexes (average age was 32.1 yrs) with symptoms of post-schizophrenic depression (F20.4 according to ICD-10) were examined by using clinical and psychometric methods in the dynamics of shift-like schizophrenia. HAMD-17, PANSS and CGI-S scales were applied. All the patients were subdivided into groups: mild, moderate and severe depressions. Valdoxan was used at a dose of 25-50 mg/day for 28 days along with preceding antipsychotic therapy at maintenance doses. Evaluation of the efficacy of treatment was carried out according to percentage reduction of average total score (ATS) in dynamics. RESULTS: A significant effect of valdoxan, with 73.5% of PANSS score reduction and quicker response to treatment, was identified. Therapeutic effect of valdoxan on separate components of PSD was uneven. The decrease of depressive disorders per se assessed by HAМD-17 and PANSS G-subscale was equally high (78.4 and 78.2%, respectively). Therapeutic reduction of negative disorders according to PANSS N-subscale was the lowest, at the level of 'good' effect (53.6%). In 27.3%, negative disorders were irreversible and were assessed as schizophrenic defect; in 72.7% of patients they were diagnosed as 'secondary' negative symptoms in atypical depression. In the subgroups of mild, moderate, and severe depression, the reduction of negative disorders was 62.4; 44.2 and 60.8%, respectively, and that of total PANSS score were 81.5; 66.1, and 78.6%, i.e. there was no correlation between these variables. CONCLUSION: Agomelatin (valdoxan) is an effective medication for optimization of methods of PSD treatment, providing the therapeutic effect at the level of significant or complete reduction of symptoms. The quality (depth) and rate of formation of response in the dynamics of course treatment are determined not by the severity of depressive disorders in PSD structure, but by the ratio between negative (deficit) symptoms and 'secondary' symptoms, reflecting the degree of progression of the main disease.

[A role of interactions between N-methyl-D-aspartate and dopamine receptors in facial emotion recognition impairment in schizophrenia]. / Rol' vzaimodeistviia genov NMDA- i dofaminovykh retseptorov v narushenii raspoznavaniia émotsional'noi mimiki pri shizofrenii.

AIM: To search for genetic mechanisms of facial emotion recognition (FER) impairment, one of the features of schizophrenia that affects social adaptation of patients. Based on the view implicating the interplay between dopaminergic and glutamatergic systems into the pathogenesis of schizophrenia, authors explored the interaction effects of the C366G polymorphism in the GRIN2B gene encoding NMDA receptor subunit NR2B with ANKK1/DRD2 Taq1A and 48-VNTR DRD4 polymorphisms on FER. MATERIAL AND METHODS: GRIN2B -DRD2 interaction effects were studied in a sample of 237 patients and 235 healthy controls, GRIN2B - DRD4 in 268 patients and 208 controls. RESULTS AND CONCLUSION: Both effects were significant in combined samples of patients and controls (GRIN2B X DRD2, F=4.12, p=0.043; GRIN2B X DRD4, F=6.43, p=0.012). Further analysis confirmed the interaction effect of GRIN2B and DRD2 polymorphisms on FER in patients with schizophrenia. In patients with a less efficient allele of the DRD2 in the absence of the minor allele of the GRIN2B C366G polymorphism, the results were close to normal values while patients with minor alleles of both polymorphisms showed the worst results. This finding is in line with the conceptions on a possible role of NMDA-receptor hypofunction and D2-mediated regulation of NMDA-receptor activity in FER impairments in schizophrenia.