[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).

[Transfer from paliperidone of one-month action to paliperidone of three-month action in schizophrenia spectrum disorders: clinical aspects, pharmacological strategies, therapeutic prediction]. / Perevod s paliperidona odnomesyachnogo deistviya na paliperidon trekhmesyachnogo deistviya pri rasstroistvakh shizofrenicheskogo spektra: klinicheskie aspekty, farmakologicheskie strategii, terapevticheskaya prediktsiya.

OBJECTIVE: To analyze clinical and therapeutic features of the transfer of patients with schizophrenia spectrum disorders from paliperidone palmitate of one-month action (PP-1M) to paliperidone of three-month action (PP-3M). MATERIAL AND METHODS: Data on the psychopharmacological therapy regimens of 677 patients with verified diagnoses of schizophrenia spectrum disorders (F20, F21, F25) treated with PP-3M drugs after PP-1M therapy were studied. RESULTS: The study showed the high efficacy of ultra-long-acting paliperidone therapy in 82.2% of patients with schizophrenia spectrum disorders. The unfavorable dynamics of the mental state in patients when transferring from the drug PP-1M to PP-3M was 14.0%, the return to therapy with PP-1M or tablet forms was 3.8%. Successful management of patients on PP-3M was not associated with sex and age, but was correlated with some clinical and therapeutic indicators. The most successful therapy with PP-3M was noted with the earlier appointment of PP-3M mainly as monotherapy, provided the previous stable condition on shorter-acting paliperidone preparations (including tablet forms). Predictors of a favorable prognosis of PP-3M therapy are also diagnostic categories such as paranoid schizophrenia, episodic type of course with increasing or stable personality changes and pronounced affective disorders in the structure of the clinical picture of the disease. CONCLUSION: The results demonstrate the high efficacy of PP-3M and its significant rehabilitation potential, which allows improving the quality of life and social functioning of patients, as well as optimizing the provision of psychiatric care to this contingent of patients, which is of particular importance in the conditions of the COVID-19 pandemic.

[Prognosis of the functional outcome of schizophrenia using a multigene panel]. / Otsenka prognoza funktsional'nogo iskhoda shizofrenii s pomoshch'yu mul'tigennogo testa.

OBJECTIVE: To compare the groups of schizophrenic patients with different levels of functional outcome and different frequency of risk variants in polymorphic loci of five candidate genes to create a multigene panel and to test its predictive ability for long-term outcome of the disease. MATERIAL AND METHODS: According to the proposed typology, the patients included in the studies were divided into three groups, which differed in the level of social functioning. Group 1 was characterized by the highest level, in group 2 this indicator was significantly lower, and in group 3 the lowest. The multigenic panel included genes for serotonin receptor type 2a (5-HTR2A T102C), serotonin transporter (5-HTTLPR), C-reactive protein (CRP -717A>G), angiotensin II receptor type 1 (AGTR1 A1166C), and brain neurotrophic factor (BDNF Val66Met). A multi-gene risk score was calculated for each patient by summing the total number all his/her risk alleles. For each polymorphism, a score of 2 was assigned to homozygous high-risk genotypes, a score of 1 to heterozygous genotypes and a score of 0 to homozygous low-risk genotype. Accordingly, the multi-gene risk score for a patient could vary from 0 to 10 risk alleles. RESULTS: A significant effect of the group on the multi-gene risk score was shown (p<0.0001). Between-group differences were significant as well (p<0.01). In group 1, there were no carriers of ≥6 risk alleles, and the number of carriers of less than 5 alleles exceeded 50%. In group 2, the number of carriers of ≥6 risk alleles was 19.4%, and in group 3 - 31.7%. Moreover, in these groups there were no carriers of 0-2 risk alleles, while in group 1 their number was 20.7%. CONCLUSION: The multi-gene risk score predicts the level of functional outcome in patients with schizophrenia. In the case of a smaller number of risk alleles (0-4) in an individual, a favorable functional outcome can be predicted with a high probability in the long-term period of the disease.

[Comorbidity of somatic diseases in psychiatric patients]. / Komorbidnye somaticheskie rasstroistva u patsientov s psikhicheskimi zabolevaniyami.

OBJECTIVE: To study the prevalence of somatic diseases in patients with mental disorders based on the results of medical examination in Moscow mental health clinics in 2018. MATERIAL AND METHODS: A retrospective analysis of the results of the clinical examinations of 6492 outpatients, which accounted for 79.5% of patients who underwent medical examination in this time period. RESULTS: Comorbid somatic diseases were found in 4883 (75%) patients. Hypertension and non-insulin-dependent diabetes mellitus were most frequent with the prevalence higher than in the general population of the Russian Federation. Patients with diagnosed schizophrenia, along with hypertension and diabetes mellitus, have found to be at increased risk of diseases of the endocrine system and metabolic disorders. The incidence of the mentioned diseases is not higher than that reported in literature. CONCLUSION: The higher prevalence of socially relevant diseases (hypertension, diabetes mellitus) among patients with mental disorders demands the development of strategies for prevention, early detection and treatment of these diseases in psychiatric patients.

[Features of the long-term course of young-onset schizophrenia: a clinical and follow-up study]. / Osobennosti dlitel'nogo techeniya yunosheskoi shizofrenii (kliniko-katamnesticheskoe issledovanie).

OBJECTIVE: To determine the features of the course of young-onset schizophrenia based on the long-term follow-up results (20-25 years). MATERIAL AND METHODS: The results of the long-term follow-up study of 320 patients with young-onset schizophrenia referred for psychiatric care in an outpatient clinic in Moscow from 1990 to 1994 were analyzed. Correlations between typological variants of the patient's condition during the follow-up and features of the dynamics of the schizophrenic process at different stages of the disease were studied. Clinical-psychopathological, clinical follow-up, clinical-epidemiological and a psychometric method were applied. RESULTS AND CONCLUSION: The severity of symptoms at all stages of the disease correlates with typological variants of conditions at the stage of long-term follow-up. In the first type, there is an accumulation of personality desorders and the most prognostically favorable variants of the initial stage, manifestations of psychotic states, the disease often manifests with only one episode and has a regressive character, the disease process fades quite quickly, mainly high-and medium-quality remissions are formed. In the second type, there is an accumulation of less favorable signs - prolonged variants of the initial stage with a predominance of negative disorders, hallucinatory-delusional manifestations of psychoses with exacerbations after 10-12 years, the high frequency of progressive forms of disease course and remissions of moderate to low quality. Type 3 is characterized by the most severe combinations of positive and negative symptoms, paranoid forms of the initial stage, paranoid and catatonic manifestations of psychoses, a high number of relapses at all stages of the course, low-quality remissions and frequent transition of the disease to a continuous form.

[Clinical-epidemiological and social-demographic characteristics of patients newly diagnosed with schizophrenia in 2013-2017]. / Kliniko-epidemiologicheskaya i sotsial'no-demograficheskaya kharakteristika patsientov s vpervye ustanovlennym diagnozom «shizofreniya¼ v 2013­2017 gg.

OBJECTIVE: To evaluate the dynamics of clinical-epidemiological and social-demographic characteristics in a continuous sample of patients with newly diagnosed schizophrenia in 2013-2017. MATERIAL AND METHODS: An analysis of the continuous study of medical records of 4708 patients, aged 14 to 77 years, with newly diagnosed schizophrenia, who referred to Moscow psychoneurological dispensaries, was performed. RESULTS AND CONCLUSION: Patients of young working age prevailed in the sample; the onset of symptoms of the disease in men was noted at an earlier age than in women. The disease at an early stage was accompanied by a professional decline and a significant disability. Schizophrenia was most frequently diagnosed in the first visit. There was a clear correlation between an increase in the number of compliance violations and an increase in the duration of the disease. Assessment of the frequency of visits to primary care psychiatrists and admissions to hospitals and day hospitals indicates the increased effectiveness of outpatient psychiatric services in Moscow.

[Neurophysiological characteristics of juvenile schizophrenia patients examined at the very remote follow up stage]. / Neirofiziologicheskaya kharakteristika bol'nykh yunosheskoi shizofreniei na etape otdalennogo katamneza.

OBJECTIVE: To determine neurophysiological characteristics of patients with long-term follow up (>20 years) and to find correlations between neurophysiological parameters and clinical features of schizophrenia. MATERIAL AND METHODS: The patients were divided into three groups: with predomination of personality changes (group 1, n=17), with negative disorders (group 2, n=23) and with positive and negative disorders (group 3, n=40). A psychopathological method and electroencephalography with evoked potentials testing were used. RESULTS AND CONCLUSION: In group 3, the statistically significant higher frequencies of theta-rhythm and lower of alpha-rhythm were found. Also, theta frequency correlated with PANSS positive scores. The significant intergroup differences by auditory oddball P300 were lacked. The findings are discussed in view of the hypothesis of theta-rhythm as a marker of hippocampal-prefrontal connectivity.

[Relationships of rs7341475 polymorphism and DNA methylation in the reelin gene with schizophrenia symptoms]. / Sviaz' polimorfizma rs7341475 i metilirovaniia DNK v gene rilina s proiavleniiami shizofrenii.

AIM: To study the role of polymorphism rs7341475 and methylation of the reelin gene in symptoms of schizophrenia and semantic verbal fluency. MATERIAL AND METHODS: Genotypes at the locus rs7341475 were identified in 556 patients with schizophrenic disorders. PANSS scores were obtained for 549 patients and 221 patients performed a test for semantic verbal fluency. The association of the reelin promoter methylation with the PANSS and verbal fluency measures was evaluated in 35 patients. A five-factor model of the PANSS was used. RESULTS: The interaction effect of sex with genotype on the PANSS scores was found (F=2.70, p=0.020). Schizophrenic men homozygous for a common allele G had the lowest scores of the positive syndrome. Verbal fluency was related to the reelin promoter methylation. CONCLUSION: The results suggest that polymorphism rs7341475 may be associated with the variability of positive symptomatology in schizophrenic men. At the same time, the reelin gene methylation pattern, which consists of a higher methylation level in the region of the transcription start site and a lower one in the distal region of the promoter, may be beneficial for verbal fluency.

[The interaction effect of ANKK1/DRD2 TaqIA and HTR2C Cys23Ser on approach motivation in schizophrenic patients and normals]. / Éffekt vzaimodeistviia polimorfizmov ANKK1/DRD2 TaqIA i HTR2C Cys23Ser na pobuditel'nuiu motivatsiiu u bol'nykh shizofreniei i zdorovykh.

AIM: To evaluate the association of the DRD2 gene and DRD2 x HTR2C interaction with hedonic and activational aspects of approach motivation in schizophrenia. MATERIAL AND METHODS: Genotypes at polymorphic loci DRD2 rs1800497 and HTR2C rs6318 (Cys23Ser) were identified in a sample that included 174 patients with schizophrenic spectrum disorders and 268 healthy subjects without a family history of psychoses. The participants completed the BIS/BAS and Temporal Experience of Pleasure Scale (TEPS). RESULTS AND CONCLUSION: A MANCOVA with sex and age as covariates revealed the effect of the 'DRD2 x HTR2C x diagnosis' interaction on the BAS scores (p=0.033). The effect was significant for the Fun-Seeking and Drive scales. Among patients, the carriers of the DRD2 TT/CT x HTR2C GG/G genotype showed the highest scores on the both scales, and those with the minor alleles in the two loci had the lowest ones. Differences between these groups were nominally significant for both the Fun-Seeking and Drive, but did not survive the correction for multiple comparisons. Among controls, subjects without minor alleles demonstrated the highest scores on these two scales. They differed significantly from the carriers of the DRD2 TT/CT+HTR2C GG/G genotype on the Fun-Seeking (p=0.008). No effects of DRD2 and HTR2C on TEPS scores were found. In general, the results of the study can be interpreted in favor of the hypothesis about the role of the HTR2C and DRD2 genes interaction in the variability of the activational aspects of approach motivation in schizophrenia and healthy subjects. However, the lack of differences survived correction for multiple comparisons makes it difficult to interpret the revealed effects.

[Risk of manifestation of endogenous psychosis in patients with nonpsychotic mental disorders of juvenile age].

OBJECTIVE: To identify people at high risk of endogenous psychosis in patients of juvenile age with nonpsychotic mental disorders. MATERIAL AND METHODS: Authors examine 49 patients of juvenile age with symptoms of nonpsychotic mental disorders (ICD-10 diagnoses of mood disorder, personality disorder or schizotypal disorder). RESULTS: In all cases, symptoms related to signs of the premorbid stage of endogenous psychosis (schizophrenia and schizoaffective psychosis) were identified. After psychopharmacological treatment, an incomplete (<30%) reduction of psychopathological disorders recorded at admission was found in 24.5% of patients. Based on the response of patients to treatment, family history (having a first-degree relative with psychosis) and the diagnosis of mental disorder, it was singled out "high-risk" (20.4% patients) and "ultra-high risk" (18.4%) states for psychosis. CONCLUSION: In light of these findings, the necessity of a longitude prospective study of these patients and pharmacological interventions in outpatient conditions is discussed.

[Some electrophysiological and hemodynamic characteristics of auditory selective attention in norm and schizophrenia].

Six patients in the state of remission after the first episode ofjuvenile schizophrenia and seven sex- and age-matched mentally healthy subjects were examined by fMRI and ERP methods. The auditory oddball paradigm was applied. Differences in P300 parameters didn't reach the level of significance, however, a significantly higher hemodynamic response to target stimuli was found in patients bilaterally in the supramarginal gyrus and in the right medial frontal gyrus, which points to pathology of these brain areas in supporting of auditory selective attention.

[The association between the NRG1 gene polymorphism and cognitive functions in patients with schizophrenia and healthy controls].

NRG1 is a strong candidate for schizophrenia though its role in the pathogenesis of the disease remains unknown. One of the approaches to study mechanisms underlying the association between NRG1 and schizophrenia is to investigate the association between a gene and an endophenotype of schizophrenia, e.g., cognitive dysfunctions. Authors looked for the association of 478B14-848 и 420M9-1395 microsatellites with semantic verbal fluency, working and episodic memory in 338 patents with schizophrenia, 162 their unaffected relatives and 316 healthy controls from the Russian population. It was found associations between allele 0 at 478B14-848 (220 bp) and long-term episodic memory and between allele 0 at 420M9-1395 (274 bp) and short-term memory in schizophrenic patients. The frequency of homozygotes for 420M9-1395 was higher in the group of patients as compared to controls. In conclusion, the risk allele 0 at 420M9-1395 is associated with the short-term memory deficit while allele 0 at 478B14-848 is protective for long-term memory deficits.

Polymorphism of serotonin receptor genes (5-HTR2A) and Dysbindin (DTNBP1) and individual components of short-term verbal memory processes in Schizophrenia.

Associations between polymorphisms in the T102C and A-1438G loci of the 5-HTR2A and the P1763 and P1578 markers of the DTNBP1 gene with the overall productivity and individual subprocesses of shortterm verbal memory were studied in 4-5 patients with schizophrenia and 290 healthy subjects. Subjects were asked to reproduce immediately two lists of 10 words. The overall productivity of reproduction was assessed, along with the reproduction productivity of the first list (immediate memory or general attention), the effect of proactive interference, and the number of intrusions. Patients were significantly different from controls on all measures. Patients showed decreases in overall task performance productivity, in immediate memory productivity, and in the effect of proactive interference; fewer intrusions were seen. Both markers of the 5-HTR2A gene were associated with short-term memory productivity in the combined cohort: assessments were worse in T102C CC and A-1438G GG homozygotes. The P1763 marker of the DTNBP1 gene, conversely, had significant influences on the memory subprocesses reflected in the levels of interference and intrusions but had insignificant influence on overall productivity. Homozygotes for P1763G GG had the worst parameters. Overall, these data are consistent with the concept that these polymorphic genes are involved in different subprocesses of short-term memory both in normal subjects and in patients with schizophrenia.

Dynamics of cognitive anomalies in patients with first episodes of juvenile endogenous psychosis.

The therapeutic dynamics of neuropsychological and neurophysiological markers of impairments to cognitive functions were studied in groups of patients with first episodes of juvenile endogenous psychosis (90 patients). At the initial stage of remission, subjects were found to show improvements in processes associated with voluntary regulation of cognitive functions (due to the activity of extensive networks of cortical and subcortical structures), while more automatic processes (associated mainly with the temporal areas of the brain) remained abnormal. Changes in neurocognitive anomalies during the onset of remission were also identified in groups of patients in whom episodes had different syndromal structures - catatonic, hallucinatory-delusional, and affective-delusional.

[The role of genotype-environment interactions in the development of symptoms of anxiety and depression related to the disease burden for family].

The association of 5-HTTLPR and Val66Met BDNF genotypes with symptoms of anxiety and depression related to stress caused by severe chronic psychiatric disease of a family member has been studied. Genotyping has been conducted in the group of 214 unaffected parents of patients with schizophrenia and 100 healthy age-matched controls. The diplotype Met*ss was associated with higher scores of depressive symptoms as assessed by MMPI in the group of parents but not in the control group. The most marked differences were seen in the subgroup of parents whose children had the greatest severity of symptoms. The results suggest that the interaction of 5-HTT and BDNF genes may moderate the association between objective and subjective burden of disease.

[Serotonin receptor (5-HTR2A) and dysbindin (DTNBP1) genes and component process variables of short-term verbal memory in schizophrenia].

An association study of variations in the DTNBP1 (P1763 and P1578) and 5-HTR2A (T102C and A-1438G) genes with short-term verbal memory efficiency and its component process variables was carried out in 405 patients with schizophrenia and 290 healthy controls. All subjects were asked to recall immediately two sets of 10 words. Total recall, List 1 recall, immediate recall or attention span, proactive interference and a number of intrusions were measured. Patients significantly differed from controls by all memory variables. The efficiency of test performance, efficiency of immediate memory, effect of proactive interference as well as number of intrusions were decreased in the group of patients. Both 5-HTR2A polymorphisms were associated with short-term verbal memory efficiency in the combined sample, with the worst performance observed in carriers of homozygous CC (T102C) and GG (A-1438G) genotypes. The significant effect of the P1763 (DTNBP1) marker on the component process variables (proactive interference and intrusions) was found while its effect on the total recall was non-significant. The homozygotes for GG (P1763) had the worst scores. Overall, the data obtained are in line with the conception of DTNBP1 and 5-HTR2A involvement in different component process variables of memory in healthy subjects and patients with schizophrenia.

[The dynamics of neurocognitive functions in patients with the first psychotic episode of endogenous psychosis manifested in the juvenile age].

The dynamics of neuropsychological and neurophysiological markers of cognitive functions was analyzed in the groups of the first-episode young male patients. Totally 90 patients have been studied. At the early stage of remission, the improvement of the processes associated with voluntary regulation of cognition caused by the activity of the wide circuit of cortical and subcortical structures was found. At the same time, the more automated processes related mostly with the temporal brain areas remained abnormal. The peculiarities of neurocognitive dynamics during the development of the remission were revealed in the groups of patients with different syndrome structure of the first episode (catatonic, delusion/hallucination, affective-delusion).

Flow-mediated vasodilation and distensibility in relation to intima-media thickness of large arteries in mild essential hypertension.

Whether endothelial dysfunction in essential hypertension is a cause or a consequence of structural vessel wall alterations is not known. The purpose of the present study was to compare flow-mediated vasodilation and mechanical vessel wall properties of large arteries between never treated mild essential hypertensive patients with normal intima-media thickness (IMT) and those exhibiting intima-media thickening. We measured brachial and carotid artery diameter and distension by Doppler frequency analysis of vessel wall movements in M-mode in ten essential hypertensive patients with normal carotid artery IMT (HYP1), in ten patients with increased IMT (HYP2), and in 13 normotensive control subjects (CON). Thereafter, we measured changes in brachial artery (BA) diameters during distal reactive hyperemia after 4 min of forearm occlusion. Nitroglycerin-mediated vasodilation was measured to assess endothelium-independent vasodilation, and BA blood flow was estimated using a pulsed Doppler system. Intima-media thickness of the carotid arteries was examined by high resolution B-mode ultrasound. IMT was 0.66 +/- 0.02 mm in the HYP1 group, 0.84 +/- 0.03 mm in the HYP2 group (P < .01 v HYP1, P < .01 v CON), and 0.71 +/- 0.04 mm in the CON group. Forearm occlusion was reduced in both the HYP1 group (3.4% +/- 3.6%, P < .01 v CON) and the HYP2 group (6.4% +/- 1.5%, P < .05 v CON) when compared with the CON group (16.5% +/- 2.8%). Nitroglycerin-mediated vasodilation and BA blood flow were not different between study groups. BA distension (as well as carotid artery distension) was significantly lower in the HYP1 group (52 +/- 6 microm, P < .05 v CON), but not in the HYP2 group (72 +/- 10 microm) when compared with the CON group (88 +/- 13 microm). The data suggest that endothelial dysfunction and reduced distensibility of large arteries in patients with essential hypertension occur in the absence of structural vessel wall alterations.

[The antihypertensive activity of benazepril in the long-term treatment of hypertension patients and its effect on adrenal cortical function]. / Antigipertenzivnaia aktivnost' benazeprila pri dolgosrochnom lechenii bol'nykh gipertonicheskoi bolezn'iu i vliianie ego na funktsiiu kory nadpochechnikov.

Changes in arterial hypertension, heart rate and adrenocortical hormones (11-OCS, aldosteron, progestins) in the blood and 24-h urine were followed up in the course of 24-week use of angiotensin-converting enzyme inhibitor benazepril (10-20 mg once a day) in 24 patients with mild and moderate essential hypertension (EH) included in a placebo-controlled randomized study. A 2 and 24-week antihypertensive response was achieved in 75 and 71% of patients, respectively. 24-h urinary excretion of corticosteroids before the treatment was increased. After the treatment benazepril reduced excretion of 11-OCS by 42%, but not of aldosteron the levels of which decreased only within the first 2 weeks of treatment. The above trends in changes of gluco- and mineralocorticoid activity should be taken into consideration in long-term treatment of EH with inhibitors of angiotensin-converting enzyme.

[Effectiveness and tolerance of benazepril versus captopril in patients with hypertension]. / Effektivnost' i perenosimost' benazeprila v sravnenii s kaptoprilom u bol'nykh gipertonicheskoi bolezn'iu.

A double blind placebo-controlled trial was performed to evaluate antihypertension efficacy and tolerance of a new inhibitor of angiotensin-converting enzyme benazepril (a single daily dose 10-20 mg) versus captopril (50 mg 1-2 times daily) in 30 patients with mild and moderate hypertension. Monotherapy with benazepril continued 8 weeks. Antihypertension efficacy of benazepril made up 71%, of captopril 64%. Side effects occurred in 2 patients on benazepril and 1 on captopril. These two drugs produced no negative effects on renal function, electrolyte and lipid metabolism, but induced glucose lowering. Thus, benazepril single daily administration in patients with mild and moderate hypertension is effective and is tolerated well.