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Introduction According to the two-factor theory of delusional belief (Coltheart. Ann N Y Acad Sci 2010; 1191 16-26), explaining the presence of a delusion requires a combination of two neuropsychological impairments. The first deficit initially prompts the delusional belief and defines its content, whereas the second deficit – aberrant belief evaluation – interrupts the rejection of a delusional belief and is common for different types of delusions. The second deficit is associated with compromised functioning of the right ventral frontal/anterior insular cortex (r-VF/AI; Darby et al. Brain 2017; 140 497-507). However, neural correlates of the first deficit in different types of delusions remain obscure. Objectives The aim of the study was to search for regions whose functional connectivity with r-VF/AI is different between patients with somatic delusions (SD) and persecutory delusions (PD) and to further clarify the results by comparing clinical groups with healthy controls. We hypothesized that each clinical group is characterized by aberrant functional connectivity between a region, associated with poor belief evaluation (r-VF/AI), and a region, presumably associated with a neuropsychological impairment specific to the corresponding type of delusions. Methods Patients with delusional disorder or paranoid schizophrenia (n = 23) and healthy controls (n = 9; 5 females; mean age 36.2 ± 1.3) underwent resting-state fMRI (Philips Ingenia 3T). Nine patients had SD (5 females; mean age 40.3 ± 7.9) and fourteen patients had PD (3 females; mean age 35.6 ± 10.2). The clinical groups were compared in terms of whole-brain functional connectivity of r-VF/AI (ROI-to-voxel analysis in CONN; RRID:SCR_009550; www.nitrc.org/projects/conn). Statistical thresholds were p < .005 voxelwise, p[FDR] < .05 clusterwise. Each clinical group was compared with controls in terms of functional connectivity between r-VF/AI and previously identified regions with between-group differences in connectivity (ROI-to-ROI analysis). Age was a covariate of no interest in all analyses. Results Patients with SD compared to patients with PD and healthy individuals had higher functional connectivity between the r-VF/AI and a cluster in the right precentral and postcentral gyri extending to supramarginal and superior frontal gyri (Figure 1). Image: Conclusions The regions whose functional connectivity with r-VF/AI was aberrant in patients with SD are involved in the processing of tactile, proprioceptive, and visceral information. Our results coincide with a suggestion that the evaluation of beliefs related to bodily sensations is disturbed in patients with SD. Research was supported by RFBR grant project 21-515-12007. Disclosure of Interest None Declared

Introduction Age-related changes of brain functional connectivity, in contrast to brain structure, are understudied in schizophrenia. Importantly, patients with schizophrenia demonstrate an increased difference between the brain-predicted age and chronological age indicating that brain structural aging may be accelerated in this mental disorder (Constantinides et al. Mol Psychiatry 2023; 28 1201-1209). Research on functional connectivity correlates of this process seems to be fruitful. Objectives We aimed to search for the brain regions whose resting-state whole-brain functional connectivity is differently associated with brain-predicted age in schizophrenia patients compared to healthy controls. Methods Eighty-three male patients with schizophrenia (age range 17.3 – 52.3; mean age 32.1 ± 10.5) and eighty-seven male healthy individuals (age range 18.3 – 53.6; mean age 31.7 ± 10.0) underwent structural MRI and resting-state fMRI (Philips Ingenia 3T scanner). Brain-predicted age was individually estimated using a model trained on independent data based on 68 measures of cortical thickness and surface area, 7 subcortical volumes, lateral ventricular volumes, and total intracranial volume, all derived from T1-weighted MRI scans (Han et al. Mol Psychiatry 2021; 26 5124-39). The associations between the brain-predicted age and the whole-brain global correlation (GCOR) were compared between groups; t-contrasts were calculated (one-way ANCOVA covariate interaction via CONN; RRID:SCR_009550; www.nitrc.org/projects/conn). The chronological age was a covariate of no interest. Results Schizophrenia patients had a higher difference between brain-predicted age and chronological age (T(168) = 2.1; p = .036; Cohen’s d = 0.32; 95% CI 0.02-0.63). Greater brain-predicted age in schizophrenia patients, compared to controls, was associated with lower functional connectivity of a region in the right Heschl’s gyrus, planum temporale, as well as central opercular and insular cortex with the rest of the brain (p < .001 voxelwise, p[FDR] < .05 clusterwise; Figure 1). Image: Conclusions Our results coincide with earlier findings on accelerated brain structural aging in schizophrenia. To the best of our knowledge, the present study is the first to indicate that this process is coupled with a decline of the whole-brain functional connectivity of a region located in the right temporal, insular, and parietal cortices, and this effect is not driven by chronological age. Further studies are needed to clarify the clinical and cognitive correlates of this decline of functional connectivity. The study was supported by RSF grant project 22-25-00706. Disclosure of Interest None Declared

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 It is still being discussed whether treatment-resistant schizophrenia (TRS) is a biological subtype which differs from non-treatment-resistant schizophrenia or is it a more severe condition that affects brain worse than non-treatment-resistant schizophrenia. However, there are few and heterogeneous studies and the etiology of TRS remains quite unclear. Objectives This study aimed to explore cortical and subcortical morphometric characteristics in TRS patients and its associations with the clinical features. The pilot stage comprises the comparison to the mentally healthy subjects. Methods 21 right-handed male patients (mean age 28.99 ± 8.08 years) fulfilling TRS criteria and 21 matched healthy controls (mean age 29.35 ± 7.41 years) underwent T1-weighted structural MRI at 3T Philips scanner and clinical examination. Images were processed using FreeSurfer 7.1.1. Cortical thickness and area, volumes of subcortical structures and separately volumes of the amygdala nuclei and hippocampal subregions were compared between groups. The morphometry data, PANSS (Positive and Negative Syndrome Scale), CDSS (Calgary Depression Scale for Schizophrenia) and daily chlorpromazine equivalent doses of antipsychotics were included in correlational analysis. Results were considered significant if they retained significance after correction for multiple comparisons. Results Compared to healthy controls, TRS patients showed decreased gray matter thickness in frontal, temporal, parietal, occipital, cingulate and insular regions (Figure 1). The temporal lobe showed the most prominent thinning of the cortex. The volumes of the amygdala, hippocampus (Figure 2) and nucleus accumbens, a number of amygdala nuclei and hippocampal subregions bilaterally were also decreased in TRS patients. The volume of the right globus pallidus, on the contrary, was increased (Figure 2). No correlations between altered cortical thickness, PANSS (positive, negative, general psychopathology scales and total score), CDSS and chlorpromazine equivalent doses of antipsychotics were found. Image: Image 2: Conclusions The widespread gray matter cortical and subcortical loss in TRS finds confirmation in the literature. The increased globus pallidus volume is an unexpected and intriguing result. Other studies demonstrated conflicting results on that point. Some studies reported possible therapy influence, others suggested possible associations with symptoms. We did not find any correlations with psychometric or therapy characteristics. It is possible that there are non-linear relationships or relationships that exist only at a certain stage of the disease. As for therapy, patients took individual medication, consisting of various antipsychotics and drugs from other pharmacological groups, and such heterogeneity could affect the results of the study. Further research is going to be carried out. Disclosure of Interest None Declared

Introduction There is strong evidence that delusions are associated with cortical and subcortical structural alterations. However, whether these abnormalities differ in different types of delusions within schizophrenia spectrum disorders remains unclear. Objectives We aimed at exploring structural neural patterns underlying influence/persecutory delusions across diagnostic categories within the schizophrenia-spectrum disorders. Methods Twenty six right-handed patients with delusional disorder (n=7) and schizophrenia (n=19), presenting with delusions were divided in two clinical subgroups. The first one was presented with persecutory delusions (n=12, 20.2-55.4 years, mean age 36.0±11.6, 2 females) and the second with delusions of influence (n=14, 21.2-47.6 years, mean age 36.7±8.4, 2 females). The control group consist of 26 matched healthy controls (20.2-53.6 years, mean age 36.3±9.9, 4 females). All participants underwent structural MRI at 3T scanner. MRI images were processed via FreeSurfer 6.0 to quantify cortical thickness (CTh) and volumes for subcortical and brainstem (midbrain, pons, superior cerebellar peduncle and medulla) structures. Results Compared to healthy controls, patients with delusions of influence showed decreased gray matter thickness in 17 cortical regions (Figure, A), and decreased volumes of thalamus bilaterally (left: F(1,35)=9.0, p=0.005; Cohen’s d=−0.8; right: F(1,35)=8.0, p=0.008; Cohen’s d=−0.8), left hippocampus (F(1,35)=8.8, p=0.005; Cohen’s d=−0.8), midbrain (F(1,35)=11.0, p=0.002; Cohen’s d=−0.9) and pons (F(1,35)=8.2, p=0.007; Cohen’s d=−0.8). Conversely, patients with delusions of persecution showed decreased thickness only in 4 cortical regions of the right hemisphere (figure, B) and no alterations in subcortical volumes compared to healthy controls. No differences in cortical or subcortical measures between two clinical subgroups survived corrections for multiple comparisons. No correlations between structural alterations and total PANSS or BABS scores were found in either clinical groups. Figure. Clusters of decreased cortical thickness according to atlas of Desikan et al. (2006) in delusions of influence (A) and delusions of persecution (B) subgroups compared to healthy controls. Image: Conclusions The findings suggest that patients with delusions of influence have more pronounced cortical, subcortical and brainstem structural deficit as compared to patients with delusions of persecution. However, the limited sample size and the lack of correlations with clinical scores do not allow to conclude definitely whether the revealed structural abnormalities underlies delusions of influence, which should be elucidated via further research. This study was supported by RFBR grant 21-515-12007 Disclosure of Interest None Declared

Introduction The main finding of a large-scale collaborative study (Rees et al. Nat Neurosci 2020;23(2) 179-184), which focused on de novo mutations in schizophrenia, was the discovery of an enrichment of these mutations in the SLC6A1 gene. This gene encodes the gamma-aminobutyric acid (GABA) transporter GAT1, thereby encouraging further research into novel schizophrenia targets within the GABA pathway. However, the gene was not highlighted in recent schizophrenia genetic studies, while typically pathogenic SLC6A1 mutations result in epilepsy, motor dysfunction, autistic spectrum disorder (ASD) and developmental delay. The absence of genetic replication for SLC6A1’s involvement in schizophrenia and the differing clinical spectrum for SLC6A1 mutations led us to study in depth one of the only three original probands from the Rees et al. 2020 study. Objectives In our comprehensive case study, we delved deep into the relationship between the SLC6A1 mutation and schizophrenia. Methods Our subject, a patient who first presented with acute mania symptoms at age 15 and was later diagnosed with schizophrenia, carried the SLC6A1 Arg211Cys mutation. Over a detailed 25-year follow-up, we conducted an array of assessments and tests, including cognitive testing, personality assessments, EEG, and 1H-MRS. Results Notably, we discovered abnormal GABA levels, potentially indicating a dysfunction in GABA reuptake, adding a new layer of complexity to our understanding. Further analysis revealed a significant correlation between the patient’s clinical picture and a polygenic background, rather than the SLC6A1 mutation. Despite having a high polygenic risk score for bipolar disorder, the dominant features of his condition were more representative of schizophrenia. Interestingly, neither the patient nor his father, who also showed a higher BP PRS, had a diagnosis of bipolar disorder. The pathogenic significance of the mutation warrants investigation in cells of neuronal origin. We generated induced pluripotent stem cells (iPSC) from the patient and his parents. This approach provides us with a platform for future investigations into the pathogenic significance of the mutation in neuronal cells. The Human Pluripotent Stem Cell Registry accession numbers of those cells are MHRCCGi001-A (patient), MHRCCGi005-A (mother) and MHRCCGi004-A (father). Conclusions In the presented case the clinical picture is rather explained by the polygenic background than by the SLC6A1 Arg211Cys mutation. The study is supported by Russian Science Foundation, grant 21-15-00124 (https://rscf.ru/project/21-15-00124) 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 Patients with amnestic mild cognitive impairment (aMCI) have a high risk of transition to Alzheimer’s disease. Analysis of potential biomarkers of conversion to dementia in this clinical group is crucial for prognosis and early intervention. Objectives The aim of the pilot study was to compare whole-brain functioning characteristics (fMRI, spontaneous activity and local coherence) in aMCI converters and non-converters to dementia. Methods Nine aMCI converters to dementia of the Alzheimer’s type (mean age 69.2 ± 8.2; 9 females) and ten aMCI non-converters (mean age 65.9 ± 6.1; 8 females) underwent resting-state fMRI (3T). All patients were followed up for three years. Baseline whole-brain amplitude of low-frequency fluctuations (ALFF) and local coherence (LCOR) were compared between groups (CONN-fMRI toolbox 19.с, https://web.conn-toolbox.org/; p < .001 voxelwise, p(FDR) < .05 clusterwise). Age was included in the analyses as a second-level covariate. Results As compared to non-converters, aMCI converters were characterized by higher ALFF and LCOR values in the cluster located in the frontal medial cortex and frontal pole bilaterally. Conclusions Frontal medial cortex and frontal pole are involved in a wide range of cognitive functions, including episodic memory and “hot” (motivational) executive control (Rolls. ProgNeurobiol 2022; 217; Friedman, Robbins. Neuropsychopharmacology 2022; 47(1) 72-89). Both increased and decreased LCOR/ALFF values in aMCI converters compared to non-converters were found, although in the other regions (Mondragón et al. Dement Geriatr Cogn Dis Extra 2021; 11(3) 235–249; Khatri, Kwon. Front Aging Neurosci. 2022; 14). It seems reasonable to clarify if the brain functional features revealed in our study are the markers of conversion to dementia in aMCI. Disclosure of Interest None Declared

Introduction Schizotypy refers to a continuum of symptoms from subclinical manifestations in the general population to severe symptoms in schizophrenia spectrum disorders. Neuroimaging studies revealed significant relationships between schizotypy and cortical anatomy in the general population. However, it remains unclear whether these structural associations has a gender specificity. Objectives The present study used structural MRI data to investigate the relationship between subclinical schizotypy symptoms and cortical and subcortical morphometric measures in male and female samples of healthy individuals. Methods 164 right-handed healthy unmedicated individuals (18.0-34.9 years, 57% females) underwent structural MRI at 3T Philips scanner. T1-weighted images were processed via FreeSurfer 6.0 to quantify cortical thickness for 34 regions-of-interest (ROIs) according to Desikan atlas and volumes for 7 subcortical structures at each hemisphere. Schizotypy levels were assessed using self-report Schizotypal Personality Questionnaire, total schizotypy score and 4 factors scores (Cognitive-perceptual, negative, disorganized and paranoid factors as per Stefanis et al. Schizophr Bull. 2004; 30 335-350) were calculated. Partial correlation analysis (ppcor version 1.1, R version 4.2.1) was used to assess the associations between ROIs cortical thickness and total schizotypy or 4 factors scores including age and sex as covariates. The same analysis was performed for subcortical volumes including intracranial volume as additional covariate. Results In male group we revealed a positive correlation between greater thickness of the left caudal middle frontal gyrus and higher total schizotypy (r=0.42, punc=0.0003, 95% CI [0.21–0.60]) and negative factor of schizotypy (r=0.49, punc

Introduction The corpus callosum (CC) is one of the important structures responsible for communication between the brain hemispheres. Its role is particularly important in cognitive tasks performance, information processing, concentration of attention, in mnestic processes. The corresponding dysfunctions are the major symptoms of schizophrenia, and hence, structural characteristics of CC in schizophrenics are in the focus of attention. Objectives The aim of the study was to analyze the microstructural and metabolic features of the corpus callosum in recently onset schizophrenia. Methods The study was carried out in 13 men with juvenile endogenous paroxysmal psychosis (disease standing ≤ 5 years after first manifestation) aged 17-27 years (median 22.0±3.1 years). The studies were carried out during unfolding remission or in remission. Control group consisted of 15 mentally healthy young men (18-28 years). MRI and 1H-MRS studies were carried out on Achieva 3T MRI scanner device (Phillips). Diffuse tensor images were obtained in the axial plane using echo-planar pulse sequence. Diffuse gradients were applied in 32 noncolinear vectors. The spectra were recorded by single voxel 1H-MRS. The spectroscopic voxel (2×1×1 cm) was placed in the CC genu region. The PRESS sequence was used (TR/TE=1500/40 msec). Results Statistical analysis showed no abnormal diffusion values in the CC splenium in the patients. Significant changes in the parameters were found in the CC genu. The values of ADC and RD increased, while FA coefficient decreased in the CC genu of patients with the initial stage of schizophrenia; PD values were normal. The increase of RD in the presence of unchanged PD indicated a decrease of water diffusion velocity and anisotropy in the direction perpendicular to the axon orientation. A typical 1H-MRS of the CC genu was presented in Figure 1. The results of statistical analysis of metabolite signal intensities in the CC genu of patients and normal subjects were presented in Figure 2. NAA level was reduced significantly in the patients. No appreciable changes in Cho values in the CC genu were detected in the patients vs. normal subjects. Image: Image 2: Conclusions The increase of RD could be caused by several factors: impairment of myelin membranes, axon damage because of impairment of axon cytoskeleton, and changed organization of fibrils. Our results showed that RD increase in patients with early schizophrenia did not conform to active demyelination, which was proven by the normal level of Cho, while axon damage, shown by low level of NAA, did not lead to PD reduction. The decrease of NAA level detected in our study indicated axonal damage in the CC genu of patients in the early stage of schizophrenia. The increase of RD in the presence of normal Cho level seemed to indicate disorders in the axon cytoskeleton damage, but not active demyelination. Disclosure of Interest None Declared

Introduction Endogenous psychoses, e.g. schizophrenia, are a pressing problem of modern medicine and biology. Among various neurobiological models of schizophrenia,much attention is paid to disturbances in the brain neural activity and metabolism. Objectives The aim of this study was to analyze dynamics of motor cortex metabolites in the norm and in early stage of schizophrenia in period of BOLD response to event related single stimulus using MRI methods (fMRI and NMR). Methods Study was performed on clinical Phillips Achieva 3.0 T MRI scanner. Volume of interest in motor cortex was localized on the base of fMRI study (EPI FFE, TR = 3000 ms, TE = 30 ms) as the zone of activation (Fig 1) caused by bottom push with the forefinger in response to single auditory stimuli transmitted with the 18 s periodicity. The BOLD signal was measured each 3 sec. 1Н МR spectra (PRESS, TE = 30 ms TR = 3000 ms) were run; FID signals for time points t = 0, 3, 6, 9, 12, 15, 18 s after stimulus were summarized (Fig 2). Thus, the synchronization of BOLD and metabolic responses to single stimulus was achieved. The same method was applied for spectra accumulation in resting state. For FID processing custom made software was used (with apodization filtering (LB = 20, GB = -5), FT and manual phase correction). NAA, Cho, Cr signal intensities for each time point were normalized to their values at t = 0 and to the volume of activated cells containing in the voxel (segmented manually). Intergroup difference and time points differences were estimated using Mann-Whitney criterion with the level of significance p

Introduction There is growing evidence to suggest that delusions in schizophrenia-spectrum disorders are associated with altered brain connectivity. Disruptions in long association fibers, such as the superior longitudinal fasciculus, are among the most consistent findings in psychosis. However, functional connectivity (FC) correlates of such structural alterations and their implications in delusional symptoms remains unclear. Objectives The study used a hypothesis-driven approach and aimed at exploring structural connectivity (SC) disruptions of the left superior longitudinal fasciculus (part with parietal terminations, SLFP) and their FC correlates in a group of psychotic patients with persistent delusions across diagnostic categories within the schizophrenia-spectrum. Methods Sixteen right-handed patients (23.1-53.8 years, mean age 39.6±8.5, 44% females) with delusional disorder (DD, n=10) and schizophrenia (SCZ, n=6), presenting with persistent delusions, and 16 matched healthy controls (23.0-56.4 years, mean age 38.9±11.1, 44%females) underwent diffusion-weighted 3T MRI (DW-MRI), while patients additionally underwent resting-state 3T fMRI (rsfMRI). DW-MRI data were processed via FreeSurfer6.0 and TRACULA to derive axial (AD), radial (RD) diffusivities and fractional anisotropy (FA) for left SLFP. rsfMRI data were processed with SPM12 and Conn v19c to calculate ROI-to-ROI FC between lateral prefrontal and inferior parietal components of the frontoparietal network (FPCN) according to Yeo atlas (Yeo et al. J Neurophysiol. 2011; 106(3) 1125-65), which is sought to represent cortical projections of the SLFP (Image). Partial rank-based correlation analysis (with age and sex as covariates, ppcor v1.1, R v4.2.1) was used to explore the associations between SC and FC measures involving the SLFP, PANSS and BABS scores. Results Compared to healthy controls, patients showed decreased AD in left SLFP [F(1, 28)=14.9, p=0.0006; Cohen’s d = −1.3, 95% CI: −2.1 to −0.5]. No RD or FA alterations were found. We revealed a correlation between AD in left SLFP and fronto-parietal FC within the FPN (r = 0.58, p = 0.031) in patients. Correlation between FC and PANSS total score (r = −0.54, p = 0.045) did not survived correction for multiple comparisons. No other correlations between SC or FC, chlorpromazine equivalents and clinical scores were revealed. Image: Conclusions The findings suggest that the structural connectivity disruptions of the SLFP may mediate FC strength within the FPN in patients with persistent delusions. However the limited sample size and the lack of correlations between connectivity measures and clinical scores do not allow to conclude definitely whether the revealed structural-functional connectivity pattern underlies delusional symptoms, which should be elucidated via further research. This study was supported by RFBR grant 21-515-12007 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 Mothers of terminally ill children experience chronic stress that can lead to physical and emotional exhaustion. A better understanding of their experiences, resources, and vulnerabilities can help plan psychological interventions. Objectives The research is aimed to study mothers’ appraisals of their life situation related to the child’s terminal illness and their coping strategies. Methods Participants: 21 women (aged 26-49) whose children were patients at the hospice. Women answered a set of open-ended questions and completed questionnaires: “Appraisal Criteria of the Difficulty of a Life Situation”, “Types of Orientations in Difficult Situation”, “Ways of Coping Checklist”. Data were analyzed with Pearson’s r. Results Planned coping was associated with evaluations of opportunity (r=0.78) and threat to the future (r=0.61). Despite the deteriorating health status of most of the children, women reported a high degree of subjective control. This might be related to outside help. Participants stated that helping by the family, doctors, and psychologists was essential. Unexpectedly, the “need for a quick and active response” score correlates with that for the coping strategy “fantasizing” (r=0.62). This can be explained by the depletion of resources; deprivation of sleep and active rest is often observed. An important feature is that half of the participants report high self-blame. Conclusions We suggest that self-blame, an analysis of opportunities, and probable future scenarios are important psychotherapy targets for mothers of terminally ill children. The consequences of threat appraisal are twofold: admitting the threat can be painful, but it also mobilizes one’s energy. Funding: The study was funded by RFBR, project number 20-013-00838. Disclosure No significant relationships.

Introduction Women with reproductive difficulties often feel stigmatized and isolated. Information concerning their specific experience can help plan psychosocial interventions. Objectives The study aims to analyze reproductive difficulties representations in women with different coping orientations. Methods Participants: 48 women (aged 24-43) from support groups arranged by the “You Are Not Alone” non-profit organization for women with reproductive issues. Based on the questionnaire “Types of Orientations in Difficult Situation”, participants were divided into three groups: approach coping (N=16), avoidance coping (N=9), ambivalent coping (N=23). Content analysis was conducted based on stories about reproduction difficulties experiences. Results Table 1 Groups Categories Approach coping Ambivalent coping Avoidance coping 1.Emotions Negative emotions 31% 43% Hope 31% Mobilization to solve the problem 48% Severe emotional state 9% 67% No emotion 38% 33% 2.Goals Birth of a child 81% 61% 44% Acceptance/inner harmony 13% 26% Understanding the cause of difficulties 7% 13% Maintaining the integrity of the body 56% 3.Worst-case scenario No child 56% 70% 33% Illness/depression/insanity 13% 44% Own death 13% 4% 22% Denial of the possibility of the worst-case scenario 19% 9% 4.Best-case scenario Having a child 100% 91% 67% Accepting infertility 6% Improving own health 33% Objective indicator: perinatal losses 6% 27% 14% Conclusions We identified three types of representation of reproductive difficulties in women: approaching the goal of having a child; avoidance (fear of own death/illness/insanity or not having a child); ambivalent coping (alternating approach/avoidance). Funding: The study was funded by RFBR, project number 20-013-00838. Disclosure No significant relationships.

Introduction Maladaptive defense mechanisms can play a role in maintaining the inadequate social and psychological adaptation of patients. Objectives This study aims to establish if denial is one of the central psychological defense mechanisms in patients with somatoform disorder. Methods 10 female patients at Moscow Clinical hospital №33 with somatoform disorder and panic attacks (aged 20 to 43) and 20 female participants of the control group (aged 19 to 35) were presented with 10 pictures of the Thematic Apperception Test. Pictures were previously annotated into 4 groups: neutral stimuli (2, 6GF), provoking self-blame / depression ideation stimuli (3GF,14, 15, 17GF), provoking aggression ideation stimuli (8ВМ, 18 GF, 9GF), provoking aggression/self-blame ideation stimuli (13 MF). We conducted content analyses of stories. Mann-Whitney U-test was used. Results Table 1 presents analyses categories, examples of stories, and group differences. Table 1 Category Example Patients,% of stories Control group,% of stories Mann-Whitney U-test Denial of interpersonal/internal conflict «It is a beautiful day. The girl is enjoying the sunlight. Her life is going well» (17GF). 90% 47%* р

Introduction The 8-item Stress Mindset Measure-General (SMM-G) is an instrument designed to assess stress-is-enhancing and stress-is-debilitating mindsets. The stress-is-enhancing stress mindset positively correlates with well-being indices and work productivity and negatively correlates with depression and anxiety scores. Mindset could be changed after a psychological, psychoeducational, or psychotherapeutic intervention. Objectives We aim to adapt the SMM-G for adolescents and to explore its factor structure and psychometric properties in a sample of Russian students. Methods A total of 564 Russian students (337 men, 229 women) from 9 universities aged 17 to 23 years (М=19,9) participated in the study. We computed reliability indicators, conducted exploratory factor analysis (EFA) and confirmatory factor analysis (CFA). Results Psychometric indicators are shown in Table 1. As a result of EFA (maximum likelihood, varimax rotation), two factors (eigenvalues 3,430 and 1,645) were extracted, accounting for 42,9% and 20,6% explained variance. Then, we tested the proposed model via CFA (Table 2).Table 1. Psychometric indicators Mean value ± std Cronbach`s alpha Test-retest reliability (n=179, one month between assessments) 1,175±0,165 0,805 0,563 The first factor includes all odd-numbered questions, while the second factor contains all even-numbered questions. This is consistent with the questionnaire’s structure, leading to a natural interpretation of factors as the stress-is-enhancing and stress-is-debilitating mindsets.Table 2. CFA results Fit indices Acceptable values One-Factor Model Two-Factor Model CMIN/DF ≤5 7,516 4,298 GFI ≥0,9 0,895 0,959 AGFI ≥0,9 0,828 0,902 CFI ≥0,9 0,680 0,890 RMSEA ≤0,08 0,107 0,076 Conclusions Russian adaptation of SMM-G has shown good psychometric characteristics and constitutes a useful assessment instrument. Disclosure No significant relationships.

Introduction Patients with schizophrenia spectrum disorders (SP) demonstrate heterogeneity in executive functions (EF) associated with the quality of outcome. However, neurobiological mechanisms of this heterogeneity are understudied. Objectives We aimed to identify features of resting-state functional connectivity (FC) within the frontoparietal network (FPN) that discriminate between SP and healthy individuals (HI) with better and worse EF. Methods Twenty-five SP (mean age 20.8±3.23, illness duration 1.3±2.1 years, all males) and twenty-six HI (mean age 25.17±3.46, all males) underwent EF assessment (4 verbal fluency tests and a modified Stroop task) as well as resting-state fMRI (3T). Results We used k-means clustering based on EF scores to divide all participants into groups with worse (15 SP, 6 HI) and better EF (10 SP, 20 HI). These groups differed in productivity of all verbal fluency tasks and performance time of the Stroop task. Differences between four subgroups (HI/SP with worse/better EF) were revealed in FC between the cingulate and lateral prefrontal cortex in the left hemisphere (ANCOVA, p-uncorrected

Introduction An impairment of anticipation processes is considered as a common deficiency in schizophrenia (Kveraga et al., 2007), however its neural mechanisms remain poorly understood. Objectives The 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. Methods 32-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. Results As 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. Conclusions The 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. Disclosure No significant relationships.

Introduction Depressive symptoms in schizophrenia have a high prevalence – up to 20-60 %, at the different illness stages. Non-pharmacological treatment, namely rTMS, seems like a promising approach that lacks side-effects typical for antidepressants. RTMS is widely applied in the treatment of depression, however the studies within schizophrenia domain are still rather few Objectives The aim was to examine a potential of neurophysiological data for prediction of the effects of rTMS in the treatment of patients with schizophrenia with depressive symptoms Methods 20 male patients with schizophrenia (F20.004, F20.014, F20.414, ICD–10) were examined at the stage of incomplete remission with predominance of prolonged (more than 6 months) treatment resistant depressive symptoms. An examination (clinical and neurophysiological (oddball ERP and EEG) fragments)) was repeated twice - before and after a course of 10 Hz rTMS (left DLPC, 2000 pulses per session, 15 sessions). Results Poor outcome was associated with initially higher coherence in alpha and lower - in beta1 EEG bands. The amplitudes of non-target N100 and mismatch negativity didn’t differ the groups of responders and nonresponders Conclusions The disturbances within brain networks of beta1 and alpha generators merit attention as potential neurophysiological markers with predictive value in rTMS treatment of patients with schizophrenia with depressive symptoms. Disclosure No significant relationships.

Introduction Schizophrenia is heterogeneous in terms of symptoms and outcome, but neurobiology of this heterogeneity is not well-studied. Local correlation analysis of fMRI data provides a measure of local coherence, i.e., average correlation between BOLD-signal in a voxel and its neighbours. Local correlation is a promising approach, and it seems important to find links between local brain coherence and schizophrenia outcome. Objectives We aimed to compare brain local coherence between schizophrenia patients with varied long-term outcomes and healthy controls (HC). Methods Patients with chronic schizophrenia spectrum disorders (37 males, mean age 41.5±5.5) and HC (17 males, mean age 38±7.7) underwent resting-state fMRI (3T). Cluster analysis based on PANSS and PSP allowed us to allocate patients into two subgroups (N = 13/24). The second subgroup had significantly more marked negative and general psychopathology symptoms and worse functioning than the first subgroup. Local coherence in the brain was compared between clinical subgroups and HC (ANOVA, p

Introduction Schizotypy is associated with increased vulnerability to schizophrenia spectrum disorders. Therefore, investigation of its brain correlates seems prominent for better understanding of schizophrenia-spectrum continuum as well as for development of biological treatments for schizotypal personality disorder. Functional alterations of prefrontal cortex (PFC) and their associations with clinical symptoms are well-known to exist in schizophrenia. However, their relevance to schizotypy remains unclear. Objectives The aim of the study was to check for associations between schizotypal traits in a non-clinical sample and whole-brain functional connectivity (FC) of lateral as well as medial PFC (lPFC and mPFC, respectively). Methods Eighty-two healthy individuals (52 females, mean age 24.8±5.48) filled out the Schizotypal Personality Questionnaire (SPQ-74) and underwent resting-state fMRI (3T). Seeds in lPFC and mPFC were taken from frontoparietal and default mode networks (atlas by Yeo et al., 2011). We analyzed correlations between four schizotypal factors (cognitive/perceptual, paranoid, negative, and disorganization; Stefanis et al., 2004) and whole-brain FC of the seeds (statistical threshold: p

Introduction Schizophrenia is associated with disturbances in neurophysiological processes. However, the relation of EEG and ERP parameters to structural supragranular cortical abnormalities, observed in schizophrenia, remains unclear. Objectives The purpose was to characterize EEG and ERP disturbances and their relationship to changes occurring in supragranular cortical layers in subjects with schizophrenia. Methods 43 first-episode schizophrenia (FES) male patients and 43 matched healthy controls (HC) underwent background EEG and standard two-tones oddball ERP recording and structural MRI at 3T Philips scanner. MRI 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) (github.com/kwagstyl/schizophrenia_gyral_sulcal). Results Theta rhythm spectral power was increased in FES while P300 amplitudes and latencies, N100 (to non-targets) amplitudes, alpha rhythm spectral power were not altered compared to HC. GSCD measures were increased in temporal, parietal and occipital cortices, whereas both GSTD and GSCD were increased in the right frontal cortex in FES. No correlations between altered EEG and supragranular thickness markers survived correction for multiple comparisons. Conclusions Presumably, theta rhythm has a widespread circuit of generators, including the cortical ones. However, we have not found correlations between EEG and supragranular markers in FES. Considering an absence of correlations between theta and hippocampal volumes (Lebedeva et al., 2020), a speculative interpretation is that the neurophysiological disturbances may be associated with a more complex patterns of more localized structural and functional impairments. Disclosure The work was supported by RFBR grant 20-013-00748.

Introduction Studies show that coping skills are factors in successful rehabilitation. Objectives The research is aimed to study the drug users` perception of the current life situation and their coping strategies. Methods Patients at the Free Narcological Clinic in Azerbaijan (n=46; 37 men, 9 women, aged 18 to 59) participated in our study after 10-12 days (stage 1) of a rehabilitation program. We used a structured interview, projective drawings (“The image of change”, “My difficult life situation”), and a questionnaire, “Appraisal Criteria of the Difficulty of a Life Situation”. The control group consisted of 35 non-drug users. Content analysis and t-test were used. Results While the majority of patients (77%) failed to describe any coping strategy they use in difficult life situations, all of them assessed their difficult life situation as under control—an outlook that was significantly more optimistic than the evaluation of the control group (р=0.009). The most frequently mentioned life goals were avoiding the problem (39%) and regaining health (37%). However, analysis of obstacles to achieving life goals shows that 49% of drug users mentioned no obstacles or indicated that “there are no obstacles”. Drug addiction as an obstacle is mentioned in only 4% of the responses; “environment of drug addicts” occurs as the main obstacle in 20%. Conclusions Drug users in stage 1 of the rehabilitation program have an unrealistic sense of control, few coping strategies, and do not perceive drug addiction as posing а serious obstacle to achieving their life goals. Funding: The study was funded by RFBR, project number 20-013-00838. Disclosure No significant relationships.

Introduction Machine learning has increasingly been applied to classification of psychosis spectrum in neuroimaging research. However, a number of multimodal studies using MRI and electroencephalography (EEG) is quite limited. Objectives To assess the power of multimodal structural MRI (sMRI) and EEG data to provide pairwise discrimination between first-episode schizophrenia (FES) patients, individuals at ultra-high-risk of psychosis (UHR), and healthy controls (HC) using machine learning algorithms. Methods 46 FES male patients, 39 UHR individuals, and 54 matched HC underwent sMRI (3T Philips scanner) and electroencephalography. T1-weighted images were processed via FreeSurfer to obtain cortical and subcortical measures. L2 regularized logistic regression was used to evaluate the efficacy of diagnostic prediction. Results The accuracies of pairwise discriminations were: 87% for FES vs HC (specificity 83%, sensitivity 91%); 77% for FES vs UHR (specificity 76%, sensitivity 79%); 75% for UHR vs HC (specificity 77%, sensitivity 73%). Conclusions Current findings suggest that the patterns of anatomical and functional variability have potential as biomarkers for discrimination between schizophrenia, UHR, and healthy subjects. Furthermore, results show that the selection and multimodality of feature types are important. Specifically, adding EEG data to morphometric measures improved accuracy rates in FES vs HC and FES vs UHR contrasts, whereas standalone EEG data provided higher accuracy compared with morphometric or multimodal data in UHR vs HC discrimination. Expectedly, predictive power for the UHR was smaller than for the FES due to its intermediate anatomical features, located between those observed in healthy controls and those found in patients. The work was supported by RFBR grant 20-013-00748

Introduction Future firefighters are trained and selected for a job requiring the ability to perform well under high stress and time pressure. Objectives The research is focused on the experimental study of fire cadets’ cognitive performance indicators (speed/accuracy) under stress. Methods The study follows Solomon Four Group Design with two variables: stress stimuli (exposure/non-exposure) and participants’ background (50 male fire cadets; 50 male civilian students). Stress stimuli consisted of emergencies’ photos, audio, videos. ECG, EMG, systolic wave amplitude, pulse transit time were measured during the experiment to determine the respondents’ stress levels. The cognitive reflection test (CRT) was performed. Mann-Whitney U-test, Spearman’s rank correlation coefficient were used. Results There were no differences between students and fire cadets in CRT time (p=0.515, students: 118.1±38.6 sec, cadets: 143.5±78.1 sec) and accuracy (p=0.246, students: 1.2±0.9, cadets: 1.4±0.9). Fire cadets in the stress exposure group (mean time=122, mean accuracy=1.22) performed CRT significantly faster (p=0.039) than non-exposed cadets (mean time=166, mean accuracy=1.56). The accuracy difference was insignificant (p=0.206). Fire cadets with prior emergency work experience (n=30, mean time=159.7, mean accuracy=1.6) were no different from other cadets (n=20, mean time=159.7, mean accuracy=1.1) both in time (p=0.289) and accuracy(p=0.07). The performance difference between civilian student groups was insignificant (exposure: mean time=123, mean accuracy=1.32; non-exposure: mean time=113, mean accuracy=1.06). Conclusions Stress exposure enhances fire cadets’ CRT performance (in speed, but not in accuracy). Emergency work experience did not contribute to this effect, which could be explained by the self-selection effect (since only people inclined to emergency work choose to become a firefighter). Disclosure No significant relationships.

Introduction Schizophrenia patients with auditory verbal hallucinations (AVH) demonstrate impaired functional connectivity (FC) between brain regions, involved in executive functions and language. However, as most studies compare patients to healthy controls, the specificity of these findings either for schizophrenia in general or for AVH is unclear. Objectives We aimed to compare whole-brain resting-state FC of main language brain regions between schizophrenia patients with and without history of AVH and healthy controls. Methods Schizophrenia male patients with (n=31; mean age 29,8±11,6) or without history of AVH (n=16; 29±12,4) and 39 healthy male controls (30±8,9) underwent resting-state fMRI on 3T Philips scanner. No between-group differences in age, illness duration, and severity of clinical symptoms except AVH were revealed. Regions of interest (ROIs) were taken from the independent fMRI study with conventional language localizer and included left inferior frontal gyrus (l_IFG) and superior temporal gyri (STG) bilaterally. Whole-brain FC of each ROI was compared between groups (ANCOVA; p

Introduction The COVID-19 pandemic situation is seen as an intense stressor. However, people process it differently. Objectives This study aims to examine the connection between life situation perception and the desirability of life changes the pandemic caused. Methods Adult participants (n=144; 01.04.2020–01.06.2020) answered open-ended questions about their current life situation experience and rated the desirability of life changes on a 10-point scale (see table 1). Content analysis and Pearson’s χ2 criterion were used. Table 1 Changes’ desirability -5 -4 -3 -2 -1 +1 +2 +3 +4 +5 Group 1 Group 2 Group 3 Group 4 Rejecting changes Accepting changes Results We annotated the participants’ responses. The content of life situations was categorized into restrictions, losses, difficulties (negative responses), acquisitions (positive responses), neutral, and ambivalent responses. Life goals were categorized into an approach to the desired outcome, avoidance of hassles, preservation of status quo, self-development, and return to prepandemic life. χ2 analysis confirms the differences between content-types and goal-types categories in 4 groups of participants: χ2(15)=43.62; p=0.002 (content); χ2(12)=27.23; p=0.01 (goals). The desirability of changes was positively linked with the ambivalent responses and responses containing self-development goals or approach-to-desired-outcome goals; and was negatively linked with the responses containing restriction-type situations and avoidance goals. Only the respondents accepting changes reported acquisitions; only the respondents rejecting changes reported a return to prepandemic life goals. Conclusions Perceived characteristics of life situations are closely connected with the desirability of life changes during the pandemic. Funding: The reported study was funded by RFBR, project number 20-013-00838. Disclosure No significant relationships.

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 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.

Introduction Anorexia nervosa (AN) is a complex condition with high comorbidity. Objectives This study aims to verify whether patients with AN are more aggressive towards themselves than towards others; namely, we measure the levels of autoaggressive/aggressive ideation, negative emotions regarding self/others, as well as self-harm behavior. Methods 10 female patients with AN (2 of them also had bulimia nervosa) and 20 female participants of the control group were presented with Structured Interview, Rosenzweig Picture-Frustration Test (P‐F), Thomas-Kilmann Conflict Mode Instrument, Buss-Durkee Hostility Inventory, I-structural Test of Ammon, Boyko Communication Aggression Inventory, Boyko Self-directed Emotion Accumulation Inventory (BSEAI). Mann-Whitney U-test and Pearson’s correlation coefficient were used. Results Table 1 Structured interview indicator Control group AN patients Suicide attempts 10% 60% Self-harm behavior 35% 60% Piercing/tattoos 20% 50% Depression (self-report) 40% 90% There were no significant differences in aggression levels between groups. However, patients with AN showed less extrapunitive reactions: blaming others, requiring others to resolve the situation (P-F, р=0.013) and more intropunitive reactions: self-blame, feeling responsible/guilty for the situation (P-F, р=0.031). AN patients had more self-directed negative emotions and impulses (BSEAI, р=0.01), more self-harm behavior (see table 1). There were no correlations between autoaggression and aggression scales in the control group, but there were 9 correlations between them in the AN group (p0.76). Conclusions Patients with AN are more inclined to self-blame, negative ideas about themselves, self-harm behavior, but have the same aggression level as the control group. The interconnection of aggression and autoaggression is different in patients with anorexia nervosa compared to the control group. Disclosure No significant relationships.

Introduction Future firefighters are selected and trained to perform well under pressure and stress. Objectives The research is focused on the experimental study of fire cadets’ memory capacity under stress. Methods The study follows Solomon Four Group Design with two variables: stress stimuli (exposure/non-exposure), fire cadets (n=50)/civilian students (n=40). Two series of The Digit Span Test measurements (DST) were performed. Heart rate, EMG, systolic wave amplitude, pulse transit time were measured during the experiment to determine the respondents’ stress levels. Results Memory capacity in fire cadets under stress (n=30) significantly increased (Wilcoxon match-pairs rank test, р = 0.001; 1st DST series, neutral stimuli: M=6.53, SE=0.17, SD=0.96; 2st DST series, stressful stimuli: M=7.3, SE=0.21, SD=1.16), the obtained effect size was medium (Cohen’s d = 0.7232). There was no significant change in memory capacity in civilian students under stress (n=20, Wilcoxon test, р=0.452; 1st DST series, neutral stimuli: M=6.78, SE=0.23, SD=1.02; 2st DST series, stressful stimuli: M=6.7, SE=0.23, SD=1.04). Moreover, there was no significant change in memory capacity in fire cadets that were not under stress (n=20, Wilcoxon test, р = 0.628; 1st DST series, neutral stimuli: M=6.88, SE=0.16, SD=0.70; 2st DST series, neutral stimuli: M=6.78, SE=0.16, SD=0.73). Systolic wave amplitude in the stress-exposed groups changed more pronouncedly in students (Mann–Whitney test, z=-2.131; p = 0.033) compared to cadets. Conclusions In most of the fire cadets, moderate stress exposure resulted in a memory capacity increase. Disclosure No significant relationships.

Introduction: The main finding of a large-scale collaborative study (Rees et al. Nat Neurosci 2020;23(2) 179-184), which focused on  de novo  mutations in schizophrenia, was the discovery of an enrichment of these mutations in the  SLC6A1  gene. This gene encodes the gamma-aminobutyric acid (GABA) transporter GAT1, thereby encouraging further research into novel schizophrenia targets within the GABA pathway. However, the gene was not highlighted in recent schizophrenia genetic studies, while typically pathogenic  SLC6A1  mutations result in epilepsy, motor dysfunction, autistic spectrum disorder (ASD) and developmental delay. The absence of genetic replication for  SLC6A1 's involvement in schizophrenia and the differing clinical spectrum for  SLC6A1  mutations led us to study in depth one of the only three original probands from the Rees et al. 2020 study. Objectives: In our comprehensive case study, we delved deep into the relationship between the SLC6A1 mutation and schizophrenia. Methods: Our subject, a patient who first presented with acute mania symptoms at age 15 and was later diagnosed with schizophrenia, carried the SLC6A1 Arg211Cys mutation. Over a detailed 25-year follow-up, we conducted an array of assessments and tests, including cognitive testing, personality assessments, EEG, and 1H-MRS. Results: Notably, we discovered abnormal GABA levels, potentially indicating a dysfunction in GABA reuptake, adding a new layer of complexity to our understanding. Further analysis revealed a significant correlation between the patient's clinical picture and a polygenic background, rather than the SLC6A1 mutation. Despite having a high polygenic risk score for bipolar disorder, the dominant features of his condition were more representative of schizophrenia. Interestingly, neither the patient nor his father, who also showed a higher BP PRS, had a diagnosis of bipolar disorder. The pathogenic significance of the mutation warrants investigation in cells of neuronal origin. We generated induced pluripotent stem cells (iPSC) from the patient and his parents. This approach provides us with a platform for future investigations into the pathogenic significance of the mutation in neuronal cells. The Human Pluripotent Stem Cell Registry accession numbers of those cells are MHRCCGi001-A (patient), MHRCCGi005-A (mother) and MHRCCGi004-A (father). Conclusions: In the presented case the clinical picture is rather explained by the polygenic background than by the SLC6A1 Arg211Cys mutation. The study is supported by Russian Science Foundation, grant 21-15-00124 (https://rscf.ru/project/21-15-00124) Disclosure of Interest: None Declared [ABSTRACT FROM AUTHOR]

Introduction: According to the two-factor theory of delusional belief (Coltheart. Ann N Y Acad Sci 2010; 1191 16-26), explaining the presence of a delusion requires a combination of two neuropsychological impairments. The first deficit initially prompts the delusional belief and defines its content, whereas the second deficit – aberrant belief evaluation – interrupts the rejection of a delusional belief and is common for different types of delusions. The second deficit is associated with compromised functioning of the right ventral frontal/anterior insular cortex (r-VF/AI; Darby et al. Brain 2017; 140 497-507). However, neural correlates of the first deficit in different types of delusions remain obscure. Objectives: The aim of the study was to search for regions whose functional connectivity with r-VF/AI is different between patients with somatic delusions (SD) and persecutory delusions (PD) and to further clarify the results by comparing clinical groups with healthy controls. We hypothesized that each clinical group is characterized by aberrant functional connectivity between a region, associated with poor belief evaluation (r-VF/AI), and a region, presumably associated with a neuropsychological impairment specific to the corresponding type of delusions. Methods: Patients with delusional disorder or paranoid schizophrenia (n = 23) and healthy controls (n = 9; 5 females; mean age 36.2 ± 1.3) underwent resting-state fMRI (Philips Ingenia 3T). Nine patients had SD (5 females; mean age 40.3 ± 7.9) and fourteen patients had PD (3 females; mean age 35.6 ± 10.2). The clinical groups were compared in terms of whole-brain functional connectivity of r-VF/AI (ROI-to-voxel analysis in CONN; RRID:SCR_009550; www.nitrc.org/projects/conn). Statistical thresholds were p <.005 voxelwise, p [FDR] <.05 clusterwise. Each clinical group was compared with controls in terms of functional connectivity between r-VF/AI and previously identified regions with between-group differences in connectivity (ROI-to-ROI analysis). Age was a covariate of no interest in all analyses. Results: Patients with SD compared to patients with PD and healthy individuals had higher functional connectivity between the r-VF/AI and a cluster in the right precentral and postcentral gyri extending to supramarginal and superior frontal gyri (Figure 1). Image: Conclusions: The regions whose functional connectivity with r-VF/AI was aberrant in patients with SD are involved in the processing of tactile, proprioceptive, and visceral information. Our results coincide with a suggestion that the evaluation of beliefs related to bodily sensations is disturbed in patients with SD. Research was supported by RFBR grant project 21-515-12007. Disclosure of Interest: None Declared [ABSTRACT FROM AUTHOR]

Introduction: It is still being discussed whether treatment-resistant schizophrenia (TRS) is a biological subtype which differs from non-treatment-resistant schizophrenia or is it a more severe condition that affects brain worse than non-treatment-resistant schizophrenia. However, there are few and heterogeneous studies and the etiology of TRS remains quite unclear. Objectives: This study aimed to explore cortical and subcortical morphometric characteristics in TRS patients and its associations with the clinical features. The pilot stage comprises the comparison to the mentally healthy subjects. Methods: 21 right-handed male patients (mean age 28.99 ± 8.08 years) fulfilling TRS criteria and 21 matched healthy controls (mean age 29.35 ± 7.41 years) underwent T1-weighted structural MRI at 3T Philips scanner and clinical examination. Images were processed using FreeSurfer 7.1.1. Cortical thickness and area, volumes of subcortical structures and separately volumes of the amygdala nuclei and hippocampal subregions were compared between groups. The morphometry data, PANSS (Positive and Negative Syndrome Scale), CDSS (Calgary Depression Scale for Schizophrenia) and daily chlorpromazine equivalent doses of antipsychotics were included in correlational analysis. Results were considered significant if they retained significance after correction for multiple comparisons. Results: Compared to healthy controls, TRS patients showed decreased gray matter thickness in frontal, temporal, parietal, occipital, cingulate and insular regions (Figure 1). The temporal lobe showed the most prominent thinning of the cortex. The volumes of the amygdala, hippocampus (Figure 2) and nucleus accumbens, a number of amygdala nuclei and hippocampal subregions bilaterally were also decreased in TRS patients. The volume of the right globus pallidus, on the contrary, was increased (Figure 2). No correlations between altered cortical thickness, PANSS (positive, negative, general psychopathology scales and total score), CDSS and chlorpromazine equivalent doses of antipsychotics were found. Image: Image 2: Conclusions: The widespread gray matter cortical and subcortical loss in TRS finds confirmation in the literature. The increased globus pallidus volume is an unexpected and intriguing result. Other studies demonstrated conflicting results on that point. Some studies reported possible therapy influence, others suggested possible associations with symptoms. We did not find any correlations with psychometric or therapy characteristics. It is possible that there are non-linear relationships or relationships that exist only at a certain stage of the disease. As for therapy, patients took individual medication, consisting of various antipsychotics and drugs from other pharmacological groups, and such heterogeneity could affect the results of the study. Further research is going to be carried out. Disclosure of Interest: None Declared [ABSTRACT FROM AUTHOR]