Introduction There is growing evidence of excitation / inhibition (E/I) balance abnormalities in schizophrenia, which might be associated with abnormal gamma frequency oscillations and glutamate concentrations. However, to the best of our knowledge, only one multimodal study have examined such associations between EEG and metabolite characteristics in patients at clinical-high risk of psychosis (CHR) so far. Objectives We aimed to investigate potential associations between GLX (glutamate + glutamine) levels and resting-state gamma-band power in CHR individuals and healthy controls (HC). Methods Twenty right-handed male patients (16-27 years, mean age 19.9 ± 2.7) fulfilling CHR criteria and 19 healthy male controls (16-27 years, mean age 21.6 ± 3.6) underwent resting-state EEG (16 leads; 10−20 system) and MR spectroscopy at 3T MRI scanner with voxels of 30×30×30mm located in left and right medial prefrontal cortex. Spectral analysis with estimation of gamma-band power (30-45 Hz) were conducted. MEGA-PRESS acquisitions were analyzed with jMRUi (ver. 5.1 Alpha), levels of GLX were calculated as a ratios to creatine + phosphocreatine (GLX/Cr). Gamma-band (30-45 Hz) spectral power and GLX/Cr were compared between groups. Correlations between EEG and metabolite data were analyzed with regression model including age and chlorpromazine equivalents as covariates. Results Compared to healthy controls, patients showed reduced spectral gamma-band power in 6 leads (Table). No alterations in GLX/Cr were detected. Positive correlations between altered gamma-power in all leads (except Cz) and GLX/Cr in left medial prefrontal cortex were revealed in CHR (F3: r=0.51, p=0.006; F8: r=0. 54, p=0.004; C3: r=0.37, p=0.037; Pz: r=0.51, p=0.039; P4: r=0.56, p=0.009). No correlations in HC group were found. Chlorpromazine equivalents did not correlate with GLX/Cr of gamma power in CHR group.Table. Results of between-group comparisons corrected for multiple comparisons Lead CHR Mean±SD HC Mean±SD p -value F Cohen’s d Cohen’s d CI 95% F3 0.97±0.62 1.4±0.64 0.0097 7.2 -0.69 -1.22 -0.16 F8 0.84±0.61 1.45±1.03 0.0072 7.8 -0.71 -1.24 -0.19 C3 0.97±0.55 1.44±0.64 0.0026 9.9 -0.79 -1.32 -0.27 Cz 1.03±0.61 1.42±0.52 0.0074 7.7 -0.70 -1.22 -0.18 Pz 1.17±0.7 1.62±0.63 0.0098 7.1 -0.68 -1.2 -0.16 P4 1.04±0.66 1.53±0.66 0.0051 8.5 -0.74 -1.27 -0.22 Conclusions The findings suggest that clinical-high risk of psychosis is associated with widespread alterations in resting-state gamma-band power. Positive correlations of such alterations with GLX/Cr and absence of such correlations in HC group are presumably indicative of disturbances in the excitation / inhibition balance in CHR individuals. This study was supported by RFBR grant 19-29-10040 Disclosure of Interest None Declared

Introduction Therapy of adolescent depression is accompanied by a number of difficulties associated with the influence of the age factor, which include the following aspects: social - with the possibility of forming a fear of stigmatization, biological – with low tolerance of psychopharmacological agents due to the immaturity of the functional systems of the body, psychological – with a combination of oppositional behavior of adolescents and their desire to “be like everyone else”. All these factors may lead to a decrease in patients’ compliance in the treatment of adolescent depression and premature refusal to continue treatment, which may provoke a relapse of the disorder. Objectives To assess the adherence of adolescent patients with a first depressive episode regarding the continuation of therapy after discharge from the hospital. Methods 124 patients (average age – 19.4) were examined after discharge from the hospital where they were treated for a depressive episode (according to ICD-10: F32.1, F32.2, F32.38, F32.8). The severity of depression during hospitalization and at discharge was assessed according to the HDRS scale. During hospitalization, 45.9% of patients (n=57) were diagnosed with severe depression (HDRS score of more than 24), 54.1% (n=67) were diagnosed with moderate depression (HDRS score of 17-23) (Zimmerman M. et al. JAD 2013; 150(2):384-8). At discharge, 35.5% of patients (n=44) had moderate depression, 38.7% of patients (n=48) had mild depression (HDRS score of more than 7-16) and only 25.8% of patients (n=32) had no depression (HDRS score of less than 7 points). This indicated the need to continue therapy after discharge. The degree of adherence to therapy and the main reasons for its refusal were analyzed using the Medication Compliance Scale (Lutova N. NIPNI, 2007; 26). Results The average duration of treatment continuation in patients with adolescent depression was 7.4±9.6 months. At the same time, 42 patients (33.9%) refused to continue therapy within 30 days after discharge from the hospital. 15 patients (12.1%) turned out to be fully compliant, following the doctor’s prescriptions. The main reasons for refusing therapy were: negative attitude to the fact of receiving therapy and visiting a psychiatrist (n=50, 40.3%), the development of side effects of therapy (n=46, 37.1%), negative attitude of relatives to the continuation of therapy (n=11, 8.9%), and negative attitude to the attending psychiatrist (n=2, 1.6%). In general, formally, the average duration of continuation of therapy coincides with the recommended 6-12 months (Sim K. et al. IGN 2015;19(2) pyv076), however, it is noteworthy that some patients tend to self-cancel therapy without the approval of the attending physician. Conclusions The results indicate a low level of adherence to therapy in patients with adolescent depression and require additional measures to improve it. The work was carried out with the financial support of the RSF grant 22-15-00437. Disclosure of Interest None Declared

Introduction Investigation of resilience mechanisms in patients with clinical high risk for psychosis (CHR) may inform clinical practice for the development of early intervention programs. Resilience mechanisms in CHR who did not transit to psychosis for a long period of observation may be more pronounced than in CHR converters. Objectives We aimed to compare CHR who did not convert to psychosis for 7.3 ± 1.7 years, patients with first-episode psychosis (FEP), and healthy controls (HC) in terms of brain functional connectivity and local coherence. Methods Twenty-seven CHR (mean age 27.5 ± 3.1), 24 FEP (mean age 20.6 ± 3.6), and 27 HC (mean age 27.3 ± 4) underwent resting-state fMRI (3T). All participants were males. Functional connectivity between 32 regions of interest (components of default mode, sensorimotor, visual, salience, dorsal attention, frontoparietal, language, and cerebellar networks; CONN functional network atlas www.nitrc.org/projects/conn) and whole-brain local coherence (LCOR; Deshpande et al. HBM 2009; 30(1) 13-23) were compared between 3 groups of participants (one-way ANCOVA) with post hoc analyses. Results CHR and HC demonstrated higher functional connectivity between the occipital cortex (visual network) and right rostral prefrontal cortex (salience network) compared to FEP. CHR also showed higher local coherence in the right calcarine and cuneal cortex than FEP (the following differences did not survive the correction for multiple comparisons: CHR>HC and HC>FEP). Conclusions Our findings on brain functional connectivity and local coherence may be considered as the markers of resilience mechanisms in patients with CHR as these parameters were different between CHR and FEP and were similar in CHR and HC. The research was supported by RFBR grant project 20-013-00748. Disclosure of Interest None Declared

Introduction There is much evidence of grey matter alterations in subjects at clinical-high risk of psychosis (CHR). Although, to the best of our knowledge, no studies have analyzed both cerebral cortex and amygdala nuclei morphometry alterations in CHR individuals. Objectives The aim of the study was to explore cortical thickness and amygdala nuclei morphometric characteristics in CHR patients. Methods Nineteen right-handed male patients (17-24 years, mean age 21.1 ± 2.1) fulfilling CHR criteria and 20 matched healthy controls (18-24 years, mean age 21.1 ± 1.8) underwent T1-weighted structural MRI at 3T Philips scanner. Images were processed via FreeSurfer 7.0. Cortical thickness (according to Desikan atlas) and volumes of 9 separate amygdala nuclei bilaterally were compared between groups. The morphometry data, SOPS, HDRS (Hamilton Depression Rating Scale) scores and chlorpromazine equivalents were included in correlation analysis. Results Compared to healthy controls, patients showed decreased cortical thickness in the left [F(1, 36) = 10.8, p = 0.002; Cohen’s d = −1.1, 95% CI: −1.8 to −0.4] and right [F(1, 36) = 10.5, p = 0.003; Cohen’s d = −1.0, 95% CI: −1.7 to −0.3] postcentral gyri, and increased cortical thickness in the right posterior cingulate [F(1, 36) = 9.9, p = 0.003; Cohen’s d = 1.0, 95% CI: 0.3 to 1.6] and the right rostral anterior cingulate gyri [F(1, 36) = 12.2, p = 0.001; Cohen’s d = 1.1, 95% CI: 0.4 to 1.8]. No changes in any amygdala nuclei were detected. No correlations between altered cortical thickness, HDRS, SOPS or chlorpromazine equivalents were revealed. Image: Conclusions The current findings suggest that volumetric characteristics of amygdalar complex are unaffected in the CHR state. The results have some inconsistency with our previous findings (Tomyshev et al. Psychiatry Res Neuroimaging. 2019; 289 26-36), which revealed only a decrease in cortical thickness in CHR individuals. However, the cross-sectional design of the current study and the lack of correlations between cortical thickness and clinical symptoms do not allow to conclude definitely whether the revealed higher cortical thickness can represents some resilience mechanisms, which will be elucidated via further research. This study was supported by RSFBR 22-15-00437 Disclosure of Interest None Declared

Introduction One of the methods for early diagnosis in individuals at clinical high-risk state for psychosis could be the identifying specific symptoms, such as thought disorders. Thought disorders may be a separate symptom, unrelated to attenuated positive symptoms (APS) with an independent predictive value. Objectives Correlation analysis of thought disorders and APS in patients at clinical high-risk state for psychosis. Methods The study included 30 young men (mean age 19.2±2.1 years) hospitalized at the clinic of the FSBSI “Mental Health Research Centre” with the APS in the first depressive episode (F32.1, F32.2, F32.28, F32.8) which is considered as clinical high-risk state for psychosis. The severity of thought impairment was assessed using the Thought, Language and Communication Scale (TLC). Subsequently was performed the search for correlations of scores on the TLC and the severity of “prodromal” symptoms, according to The Scale of Prodromal Symptoms (SOPS). Results The median value of the total score on the TLC was 20 [17.25;23.5]. The most important finding is the discovery of only minor correlations of thought disorder with “prodromal” symptoms. Indeed, the total score on the TLC correlated only with the total score on the SOPS at admission (r=0.370, p<0.05). Such symptoms of the TLC scale as «Derailment», «Incoherence», «Perseveration» did not find any correlation with prodromal symptoms (p>0.05). Conclusions The obtained data indicates the independent nature of thought disorder in patients at clinical high-risk state for schizophrenia, which leads the need to determine its own prognostic value. Disclosure of Interest None Declared

IntroductionAn impairment of anticipation processes is considered as a common deficiency in schizophrenia (Kveraga et al., 2007), however its neural mechanisms remain poorly understood.ObjectivesThe aim of the study was to analyze CNV-like slow negative waves during the pre-target stimuli waiting period in patients with the first episode of the disease.Methods32-channels EEGs during “Go / No go delay” saccadic paradigm have been recorded in 16 young male patients with illness duration less than 2 years and 18 age and sex matched healthy subjects. The delay period between fixation and target (“Go” or “No go”) visual stimulus was 2800-3000 ms. The early and late components of CNV - like slow negative waves (PMN1 and 2) have been studied in 1 sec pre-stimulus interval of delay period.ResultsAs compared to norm, the patients showed significantly increased latencies of saccades to correctly discriminated stimuli and higher percent of “errors saccades”. The amplitudes of No go-PMN1 and Go-PMN2 waves were also increased in patients. The amplitude foci of these waves were diffusely distributed in patients and mostly localized in frontal leads in norm.ConclusionsThe findings assume some violation of anticipation for action (motor or inhibitory response) processes as well as an increase of presumably cortical activation during stimulus anticipation in the “Go/No go delay” saccadic paradigm in the early stage of schizophrenia.DisclosureNo significant relationships.

Introduction The clinical high-risk for psychosis (CHR) is mainly established by the presence of attenuated positive symptoms (APS), but there is evidence of the role of attenuated negative symptoms (ANS) in the development of psychotic spectrum disorders. It is important to establish a link between APS and ANS in patients at CHR in order to improve early detection of psychosis. Objectives Establish the relationship between APS and ANS in depressive patients at CHR. Methods 130 depressive young in-patients at CHR with APS (average age 19.5) and 71 ones with ANS (average age 19.5) were examined. The HDRS scale was used to assess depressive symptoms, the SOPS scale was used to assess APS and ANS, and the SANS scale was used to assess ANS. The results are presented in median values. Results No differences were found between two groups in the severity of depressive symptoms on the HDRS scale and CHR symptoms on the SOPS scale (22 vs 23.5 and 45 vs 43 respectively). Statistically valid differences have been established between the groups in the APS severity on the sub-scale of positive symptoms SOPS: 11 and 7 (p 0.001). No differences in the ANS severity on the sub-scale of negative symptoms were detected (17 and 18.5, p=0.207). There were also no differences in the ANS severity on the SANS scale (40 and 47, p=0.163). Conclusions It has been established that patients at CHR with APS also have ANS, which may have clinical significance for early detection of psychosis. Disclosure No significant relationships.

IntroductionEarly detection of psychosis is a promising area in preventive psychiatry. The use of early intervention can prevent the first episode psychosis and improve outcomes.ObjectivesIdentification of premorbid features of depressive patients at clinical high risk for psychosis (CHR) comparing with depressive patients without CHR in order to improve early recognition of the psychotic process.Methods219 young depressive in-patients with CHR criteria for SOPS with attenuated positive and attenuated negative symptoms and 52 young depressive in-patients without CHR were examined. Presence of obstetric complications, neurodevelopmental deviance, neurological and psychiatric signs at the premorbid stage, and the level of premorbid functioning on the PAS were examined.ResultsIt has been established that depressive patients at CHR and without CHR had some obstetric complications (57.5% and 40.4%, respectively). Neurodevelopmental deviance in the first year of live was in 57.5% patients with CHR. At the age of 3-5 sleep disorders, ADHD and phobias were more common in patients at CHR than without it (58.8% and 32.7%, p=0.014). In pubertal, patients at CHR were more likely to show depression symptoms, obsessions, and aggression - 90.4% versus 76.9% (p=0.029). On the PAS scale, a decrease of the level of premorbid functioning has been observed in two groups of patients with and without CHR from the age of 12: from 12 to 15 years, 0.4 and 0.3 (p=0.004), from 16 to 18 years, 0.47 and 0.37 (p 0.001).ConclusionsPremorbid functioning were worst in patients with CHR, which indicates the possibility of early clinical detection of psychosis.DisclosureNo significant relationships.

Introduction In addition to the psychosis onset, patients at clinical high-risk (CHR) show a decrease of functioning. This may not be related to the degree and persistence of the attenuated positive symptom (APS). Other clinical factors also predict the level of remission.ObjectivesRevealing the predictors of the functioning in the 5-year follow-up in patients at CHR.Methods124 young depressive patients at CHR were examined. Depression symptoms were assessed on the HDRS scale, and the CHR symptoms were assessed on the SOPS scale. The follow-up examination was conducted after 5 years with the determination of functioning on the PSP scale. A correlative analysis of the predictors of the level of remission was conducted.ResultsThe functioning level was inversely related to the length of a depressive episode with the CHR symptoms (r=-0,432, p˂0.05), to the negative sub-scale SOPS score (r=0.312, p˂0.05) and to the symptoms of disorganization sub-scale SOPS score (r=0.246, p˂0.05) in the primary assessment. Insufficient reduction of the positive, negative symptoms and symptoms of disorganization on the SOPS during in-patient treatment was also a predictor of the worst outcome at the 5-year follow-up (r=-0,206, p˂0,05; r=-0,309, p˂0,05; r=-0,355, p˂0,05, and r=-0,349, p˂0,05, respectively).ConclusionsThere are some factors, except the severity of APS, that may be considered as the predictors of functioning level in patients at CHR.DisclosureNo significant relationships.

Introduction At present, there is no universally approach to treating patients at clinical high-risk for psychosis (CHR) without comorbid mental disorders. However, if there are revealed depressive symptoms, proper treatment becomes necessary. Objectives Establish pharmacological classes and doses of drugs that have proved effective in treating depressive patients at CHR. Methods A comparative study of pharmacological classes and doses of drugs was carried out, showing the effectiveness in treatment of 219 depressive patients at CHR and 52 depressive patients without CHR. The treatment effectiveness was carried out on the reduction of depression symptoms on the HDRS scale, and the CHR symptoms on the SOPS scale. Results A significant reduction of depression symptoms was achieved in the group of depressive patients with and without CHR on the HDRS scale (67.9% and 76.6% respectively). The reductions of the CHR symptoms were 46.1% and 53.3% respectively. There were differences between the severity of depression symptoms and CHR symptoms before and after the treatment. Both groups used antidepressants followed by the prescription of antipsychotics to increase the effectiveness of the therapy. No difference was found in the doses of antidepressants for the fluoxetine equivalent (46.0 vs 42.6 mg per day, p 0.05) and some differences were found for the average effective doses of antipsychotics for the chlorpromazine equivalent (385.4 vs 230.8 mg per day, p 0.05). Conclusions The same pharmacological classes are used for the treatment of young depressive patients with and without CHR, but the former have significantly higher doses of antipsychotics. Disclosure No significant relationships.

Introduction The course of affective disorders varies significantly in clinical practice. There are many symptoms that are not related to affective disorders that cannot be described in other nosologies. In the present study such pathopsychological phenomena similar to psychotic symptoms and related to symptoms of “schizophrenia risk” were designated as positive thought disorders (PTD). These symptoms are understood as manifestations of delusional and hallucinatory register. Objectives Aim of the study is to identify and validate the differences of neurocognitive functions among patients with positive thought disorders and at high risk of schizophrenia and patients without thought disorders. Methods In the research there were 17 patients with high risk of schizophrenia dominated by PTD (affective disorders, personality disorders, schizophrenic spectrum disorders) and 18 patients without thought disorders (affective disorders, personality disorders) in the research. Patients aged 17-25 years. Results According to the results of the The Complex Figure test, the group with a high risk of schizophrenia had significantly low results on the “simultaneity” scale and points for copying the figure (p-value 0.04 and p-value 0.03). According to the results of the Verbal fluency test, the main group had significantly lower indices on the “loss of instruction” scale and on the number of repetitions (p-value 0.021 and p-value 0.009). Conclusions In the group of patients with a high risk of schizophrenia with positive thought disorders there are neurocognitive features in the form of reduced inhibitory control and a lack of simultaneity. The most sensitive methods are the Complex figure test and Verbal fluency Test. Conflict of interest The reported study was funded by RFBR, project number 20-013-00772

IntroductionNegative thought disorders are found in various diagnoses in clinical practice. These symptoms may show a possible psychosis continuum and may be taken into account when assessing schizophrenic risk. Neurocognitive functioning of patients with negative thought disorders need to be clarified.ObjectivesAim of the study is to identify and validate the differences of executive functions between patients with negative thought disorders and patients without thought disorders.MethodsUsed a standardized neuropsychological test battery. There were 15 patients with negative thought disorders (affective disorders, personality disorders, schizophrenic spectrum disorders) and 18 patients with depressive episode without thought disorders in the research. Patients aged 17-25 years. The Mann–Whitney U test and ANOVA were used for statistical analysis.ResultsSignificant results were obtained from The Verbal Fluency Test, The Design Fluency Test, The Digit span, The Rey-Osterrieth Complex Figure and Bidstrup’s drawings (All tests have p-values less than 0.05). In the methods listed above, the results in the group of patients with negative thought disorders are significantly lower than in the group of patients without thought disorders.ConclusionsThe data indicate a violation of Executive functions among patients with negative thought disorders: inhibitory control, planning and regulation, working memory, difficulty switching, which related to left frontal lobe dysfunction. A lack of simultaneity and understanding figurative language, which is associated with right hemisphere dysfunction.DisclosureThe reported study was funded by RFBR, project number 20-013-00772

Introduction Conventional structural neuroimaging methods can identify changes in cortical thickness but cannot relate these changes to specific cortical layers due to a lack of sensitivity. However, several indirect measures sensitive to changes specifically occurring in supragranular cortical layers were developed recently (github.com/kwagstyl/schizophrenia_gyral_sulcal). Objectives The aim was to assess the ability of these novel measures to detect cortical layers thickness characteristics potentially associated with risk or resilience to developing schizophrenia. Methods 43 first-episode schizophrenia (FES) male patients, 29 non-converted individuals at ultra-high risk of psychosis (ncUHR, mean follow-up period – 6.5 years), and 43 matched healthy controls (HC) underwent structural MRI at 3T Philips scanner. Images were processed via FreeSurfer and MATLAB to derive two markers specific to supragranular thickness change: gyral-sulcal thickness differences (GSTD) and gyral-sulcal intrinsic curvature differences on pial surface (GSCD). Results GSCD measures were increased in temporal, parietal and occipital cortices, whereas both GSTD and GSCD were increased in the right frontal cortex in FES compared to HC. No GSTD or GSCD were changed in ncUHR compared to HC, and GSCD was decreased in the frontal cortex compared to FES. Conclusions Our findings from the indirect measures indicate a potential predominance of supragranular thinning in FES and suggest that a supragranular thinning in the right frontal lobe might be associated with precipitating risk and/or illness effects of schizophrenia. At the same time, no clear supragranular markers directly associated with resilience or risk mechanisms were identified. The work was supported by RFBR grant 20-013-00748.

Introduction The internet is now widely used by people with mental disorders, and it is important to understand whether the internet use can affect the mental state of such people. Objectives The aim of the study was to assess the relation between the internet usage for communication and the quality of the social adaptation in men with mental disorders. Methods 82 male patients with schizophrenia spectrum disorder (F20) were involved into the study (mean age 22±4.3). Methods: SCL-90R, “social circle” inventory (Susan L., Phillips), semi-structured interview of “internet usage” (“communicative internet usage” consists of communication in on-line games, use of the internet social networks for communication, use the internet to find new friends, maintaining relationships with relatives, friends, colleagues. Results Two groups of patients were considered: those who use internet for communicative purposes (N=61) and those who do not (N=21).According to the analysis (Mann-Witney U-test, hereinafter significance level *p<0.05), those who use the internet for communication have lower levels of psychotic symptoms (PSY) (U=446*), lower levels of “depression” (U=453*). Those who use the internet for communication have more people in social circle to spend free time (U=910,5*), having the same occupation (U=860*), having the same interests (U=867,5*) and sharing the same values (U=873*).They have more friends (U=804*), peers (U=814*), more women among friends (U=793*), more people to provide instrumental support (U=761,5*). Conclusions Patients, who use the internet for communications, have a lower levels of psychopathological symptoms and higher quality of social adaptation. This indicates a possible potential of the internet for mental health rehabilitation. Disclosure No significant relationships.

Introduction Studies examining gamma-aminobutyric acid (GABA) or glutamate in ultra-high risk for psychosis (UHR) have shown conflicting results, and a number of multimodal studies examining associations between metabolite and structural characteristics is very limited. Objectives We aimed to investigate potential associations between GABA and glutamate levels and cortical thickness in the frontal lobe in UHR individuals and healthy controls (HC). Methods 20 male UHR individuals and 19 healthy controls (HC) underwent structural MRI and MR spectroscopy at 3T Philips scanner. T1-weighted images were processed via FreeSurfer 6.0 to quantify cortical thickness for selected frontal regions labeled according to Desikan atlas. MEGA-PRESS acquisitions were analyzed with jMRUi (ver. 5.1 Alpha), levels of GABA and glutamate were calculated as ratios to creatine + phosphocreatine. Results The study revealed: 1) GABA/Cr ratios reduction in the left frontal lobe (p=0.001) which was not attributable to antipsychotic medication; 2) cortical thickness reductions in the left pars orbitalis (p=0.005) (the anterior part of the inferior frontal gyrus) in the UHR individuals compared to HC. No significant correlations between GABA/Cr ratios and cortical thickness were identified in both groups. Conclusions The findings indicate that the UHR state is associated with altered GABA levels and cortical thickness reductions in the prefrontal cortex. The results also show that GABA levels are not directly related to cortical abnormalities, suggesting that altered metabolite levels may be associated with a complex system of structural and functional impairments, rather than directly correlating with structural changes in separate cortical regions. The work was supported by RFBR grant 19-29-10040. Disclosure No significant relationships.

IntroductionInflammation is now known to be a key factor in the development of schizophrenia. In this regard, the study of the pathogenic role of inflammation in the early stages of schizophrenic process is of particular importance, making it possible to assess its activity and to predict the development of the disease.ObjectivesTo compare the dynamics of inflammatory markers in blood of first-episode psychosis (FEP) patients and people at risk signs for schizophrenia in the course of the treatment. Juvenile depression (JD) with attenuated symptoms of schizophrenic spectrum (ASSS) was investigated as a risk group.MethodsThe patients aged 17-25 years (20 people, of which 10 FEP patients (F20) and 10 JD with ASSS ones (F32.1-2, F32.38, F32.8)) were examined at admission to the hospital and at discharge. The controls consisted of 10 healthy volunteers. Symptom severity was collected using PANSS, SOPS, SANS, HDRS. The inflammation markers (TNF-α, IL-6, IL-10, leukocyte elastase (LE), CRP, α1-proteinase inhibitor (α1-PI), anti-S100-beta antibodies) were determined in blood.ResultsAn increase of inflammatory markers in both groups compared to controls was found (p<0,05). The highest values of IL-6, LE, CRP, α1-PI and anti-S100-beta antibodies in FEP patients were revealed (p=0,03). After the treatment, the positive trend of inflammatory markers in FEP patients (p<0,05), but not in JD with ASSS patients was detected (except LE activity, p<0,05).ConclusionsThe results confirm the pathogenic role of inflammation in the development of endogenous mental disorders. The inflammatory markers studied reflect the activity of the pathological process in the early stages of schizophrenia.DisclosureNo significant relationships.

Abstract Growing evidence supports role transforming growth factor-β (TGF-β) as a mediator of the myxomatous changes in the mitral valve prolapse. Recently, angiotensin II receptor blockers (ARB) emerged as a potentially effective inhibitor of TGF-β signaling. Treatment of valvular interstitial cells (VICs) with ARB resulted in effective inhibition of TGF-β-induced ECM expression. Our aim was to evaluate the effect of preoperative ARB therapy in modulation of transforming growth factor-β effects on mitral valve myxomatous degeneration. Methods A total of 233 asymptomatic patients (mean age: 53.8±12.9) undergoing mitral valve surgery for severe mitral regurgitation due to mitral valve prolapse were enrolled in our retrospective, non-randomized, single-center study. Resected abnormal segments of the mitral leaflets (segment of the posterior leaflet or the entire valve) were obtained during mitral valve repair/replacement surgery and examined by experienced pathologists. Immunohistochemical characterization of mitral valve sections was performed with the primary antibodies. Quantification was performed by counting TGF-β1 and TGF-β2 positive cells within 10 random high-power fields divided by the total number of cells in specimens. Quantification of immunohistochemical staining for collagen III was performed by measurement of staining area divided by the total area of the specimens. Results Two hundred thirty-three consecutive patients (66% males, mean age 53.8±12.9 years, range 19–80) with severe MR were enrolled in the study. According to the case reports, 43 patients (18.5%) received losartan or telmisartan before surgery and were included in study group. 190 patients (81.5%) did not receive any ARB and were enrolled in the control group. Histological examination showed disorganized collagen and elastin fibers, expansion of the spongiosa layer in both groups. However, MV specimens' immunohistochemistry revealed a lower expression of type III collagen in ARB group as compared to controls (31.3% ± 10.8% vs. 43.8% ± 15.3%; p<0.001). MV leaflets in control group showed the increased VICs density (95.3±39.9 vs. 70.0±21.7/high-power field, p=0.0001). TGF-β1 and TGF-β2 positive cells were significantly rare in the ARB than in control MV specimens (18% vs. 33%, p=0.012 and 16% vs. 38%, p<0.ehab724.15541, respectively). Expression of type III collagen and TGF-β2 positive cells count showed a weak, but significant correlation (r=0.28; p=0.ehab724.155414). The multivariate Cox analysis showed a decrease in the relative risk of valvular thickening (myxomatous degeneration) with ARB therapy (0.85; 95% CI: 0.61 – 1.17; p=0.01). Conclusions We indicate a beneficial effect of ARB treatment through the inhibition of TGF-β pathway on valvular myxomatous degeneration in patients with MVP. Modulation of the progression of MVP with such therapeutic agents may have great clinical significance. Funding Acknowledgement Type of funding sources: None.

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Improvement in malignant ventricular arrhythmias (VA) has been reported after mitral valve surgery in some mitral valve prolapse patients (MVP) with severe degenerative mitral regurgitation. Mitral annular disjunction, posterior systolic curling, and mitral annular abnormal contractility are associated with arrhythmic MVP and underwent correction during the mitral valve repair. However, mitral valve disease progression and ventricular arrhythmic substrates (left ventricular fibrosis of papillary muscles and basal posterior wall) could be potential substrates for persistent malignant arrhythmias even after surgical correction. Our aim was to evaluate the risk factors of persistent VA after mitral valve repair in Barlow’s disease patients in six-year follow-up. Methods 30 consecutive patients (mean age 53.1 ± 9.4, 47% male) who underwent mitral valve repair for severe mitral regurgitation (MR) due to mitral valve prolapse were enrolled in our observational, prospective, single-center study. Resected abnormal segments of the mitral leaflets were examined by experienced pathologists for signs of myxomatous degeneration. Transthoracic echocardiography and 24-hour Holter monitoring were performed pre- and postoperatively annually. PVCs and nonsustained ventricular tachycardia (VT) runs were reviewed. Results All patients survived the operation. There was only one sudden cardiac death on sixth year of follow-up. During 173 person-years of follow-up 3 patients (10%) had developed recurrent moderate to severe (≥2) MR. The total number of PVCs and non-sustained ventricular tachycardia runs dropped significantly in 1st (p=.04, Wilcoxon matched pairs test) and 2nd (p=.03), years of postoperative follow-up. Postoperative incidence of PVCs and VT correlated strongly with postoperative end-diastolic LV diameter (EDD rs=.69; p=.005), moderate negatively with LV ejection fraction (EF rs=-.55; p=.001). Advanced myxomatous degeneration assessed by pathologists and MV posterior leaflet’s thickness ≥5 mm after repair assessed by echocardiographer associated with postoperative PVCs and VT (rτ=.58; p=.045 and rs=.62; p=.002, respectively). Recurrent MR also strongly associated with postoperative PVCs and VT (rs=.76; p=.0018). In univariate analysis, advanced myxomatous degeneration (p=.008), postoperative end-diastolic LV diameter (p=.001), and low EF (p=.003) were identified as risk factors of persistent PVCs/VT after surgery. Conclusions Advanced myxomatous degeneration assessed by pathologists or echocardiographer and postoperative left ventricular remodeling are associated with persistent malignant ventricular arrhythmias. Further investigation in larger cohorts to evaluate the association between degenerative mitral valve disease and ventricular arrhythmias is needed.

IntroductionThe identification of the psychosis high-risk state in help-seeking patients with depressive symptoms offers the possibility of detection and intervention at the early stages of schizophrenia.ObjectivesEstimating the 5-year follow-up rate of the manifestation of psychosis and levels of functioning in patients with the clinical high-risk state and depressive symptoms.Methods81 inpatients (average age 19.6 years) with depressive symptoms and attenuated psychosis (60 patients with APS and 21 patients with BLIPS). Average duration of inpatient treatment was 56.3 days, antidepressant therapy (mean dosage equivalent to fluoxetine 43.1 mg/day) and antipsychotic therapy (mean dosage equivalent to chlorpromazine 408.9 mg/day) were conducted. All patients were followed up after discharge at least during 5 years (average follow-up 7.1 years). Levels of functioning were assessed on the PSP scale.ResultsThe manifestation of psychosis was identified in 21.0% (17 patients) (on average in the third year of follow-up), complete symptomatic and functional remission was established in 11.1% (9 patients) (PSP 100-81), complete symptomatic and incomplete functional remission was established in 27.2% (22 patients) (PSP 80-61). Incomplete symptomatic and incomplete functional remission – in 24.7% (20 patients) (PSP 60-41) and 13.5% (11 patients) (PSP<40).ConclusionsThe combination of antidepressants and antipsychotics therapy in patients with the clinical high-risk state for psychosis reduced the risk of psychosis manifestation but did not significantly affect the level of outcome compared to other studies.DisclosureNo significant relationships.