Psychobiotics are a group of probiotics that affect the central nervous system related functions and behaviors mediated by the gut-brain-axis via immune, humoral, neural, and metabolic pathways to improve not only the gastrointestinal function but also the antidepressant and anxiolytic capacity.

To assess the efficacy the combination of selective serotonin reuptake inhibitors antidepressants (SSRI) and probiotic supplement containing Lactobacillus Plantarum CECT7485 and Lactobacillus Brevis CECT7480 (PLANTARUM) in patients with mild-to-moderate depression.

Sixty patients with mild-to-moderate depression (according to ICD-10 diagnostic criteria for mixed anxiety and depression disorder, F41.2) were included in an 8-week open label study. Thirty participants received either SSRI antidepressants with PLANTARUM at a dose of 1.0 × 109 CFU once per day. Thirty patients received SSRI antidepressants only without probiotics intake. The severity of depressive symptoms was assessed using Hamilton Depressive Rating Scale (HDRS) and Patient Health Questionnaire (PHQ-9).

After 8 weeks intervention, a clinically significant reduction of HDRS total score (from 45,6±6,1 to 22,5±3,7) was detected in patients with mild-to-moderate depression who received SSRI antidepressants and PLANTARUM (p˂0,001), compared with participants who didn’t receive probiotics (p>0,05). A significant reduction of PHQ-9 total score (from 19,3±2,9 to 9,0±1,9) was identified in patients with mild-to-moderate depression who received SSRI antidepressants and PLANTARUM (p˂0,05). However, the participants received SSRI antidepressant only didn’t meet a clinically significant reduction depressive symptoms (p>0,05) by PHQ-9 scale.

The combination use of SSRI antidepressants and probiotic supplement PLANTARUM significantly reduced the depressive symptoms.

None Declared

The underlying neurobiology of early-life stress (ELS)-induced major depressive disorder (MDD) is not clearly understood. miRNAs, a subclass of noncoding RNAs, are estimated to regulate 20-90% of genes in the genome. Previous studies identify differences in miRNA expression following MDD and ELS, but there is limited research on a direct link between changes in serotonin signaling and miRNAs in response to ELS.

In this study, we used MS and environmental enrichment to study serotonin signaling in the PFC and its regulation by miRNAs. Because women are more likely to develop MDD, but there is no strong evidence of sex differences in the experience of ELS, we were interested to test for sex differences. We hypothesized that genes in the serotonin signaling pathway would be altered by ELS and potentially recovered by enrichment.

We used maternal separation (MS) as a rodent model of ELS and tested whether microRNAs (miRNAs) target serotonin genes to regulate ELS-induced depression-like behavior and whether this effect is sex dependent. We also examined whether environmental enrichment prevents susceptibility to depression- and anxiety-like behavior following MS and whether enrichment effects are mediated through serotonin genes and their corresponding miRNAs.

MS decreased sucrose preference, which was reversed by enrichment. Males also exhibited greater changes in forced swim climbing and escape latency tests only following enrichment. Slc6a4 and Htr1a were upregulated in the frontal cortex following MS. In male MS rats, enrichment slightly reversed Htr1a expression to levels similar to control rats. miR-200a-3p and miR-322-5p, which target SLC6A4, were decreased by MS, but not significantly. An HTR1A-targeting miRNA, miR-320-5p, was also downregulated by MS and showed slight reversal by enrichment in male animals. miR-320-5p targeting of Htr1a was validated in vitro using SHSY neuroblastoma cell lines.

Altogether, this study implicates miRNA interaction with the serotonin pathway in ELS-induced susceptibility to depression-related reward deficits. Furthermore, because of its recovery by enrichment in males, miR-320 may represent a viable sex-specific target for reward-related deficits in major depressive disorder.

None Declared

Resistant to treatment depression (RTD) is a prevalent disease that implies functional impairment and high resources consumption. Theta Burst Transcranial Magnetic Stimulation (TBS) in dorsolateral prefrontal cortex (DLPFC) is a novel therapy that has shown experimental efficacy and as an adjuvant strategy in RTD. The implementation of TBS in the Public National Health Service requires cost-effective protocols that achieve earlier responses and higher rates of effectiveness, and whose design is based on biomarkers of response so as to adequately select candidate patients.

To assess the efficacy and safety of novel bilateral and unilateral intensive/spaced protocols of TBS in outpatients with unipolar/bipolar RTD compared with sham stimulation. Specific objectives: I) Comparison of mood change at the end of TBS protocol in the groups and maintenance of its effect at 3 months; II) Characterization of cerebral connectivity and metabolism patterns related to the effects of TBS; III) Analysis of the interaction between clinical and neuroimaging predictors so as to determine a RTD profile of patient that can benefit from TBS.

A two-year randomized double-blind clinical trial with 96 outpatients with TRD will be carried out. Participants will be randomized in three groups (active bilateral, active left and sham right and sham bilateral) to receive 22 active/sham sessions of continuous TBS (right DLPFC) and intermittent TBS (left DLPFC) during 6 weeks (w 1-2: 5 sessions/w, w 3-6: 3 sessions/w). Assessments of mood and side-effects will be carried out weekly. Functional neuroimaging will be a a simultaneous PET/MR acquisition previous and at the end of TBS treatment. Between-group comparisons of efficacy in terms of Hamilton Depression Rating Scale (HDRS-17) from basal to 6th week will be performed using controlled mixed regression models. Between-group comparisons will be made at baseline and after treatment, studying the imaging biomarkers obtained. Clinical and neuroimaging predictors of response will be integrated in machine learning models.

The expected results of the project are summarized in the following hypotheses: 1) The intensive and spaced protocols of TBS as an adjuvant antidepressant treatment will have greater efficacy than sham stimulation in patients with TRD. 2) Both protocols will be safe, with mild side effects. 3) Unilateral and bilateral TBS protocols will involve changes in connectivity and cerebral metabolic consumption mainly in regions of the fronto-cingulo-temporal circuitry. 4) PET/MR imaging biomarkers will allow us to differentiate whether patients have responded to treatment with TBS.

This project may help to improve resistant to treatment depression management by personalizing TMS treatment with the use of neuroimaging biomarkers.

None Declared

Depression is the disease with the greatest burden of disability. Despite pharmacological options, up to 30% of depressions are considered resistant to treatment (RTD). Theta burst transcranial magnetic stimulation (TBS) on the dorsolateral prefrontal cortex allows the application of shorter protocols and with longer-lasting effects than conventional TMS. Its implementation in the Public Health System requires the design of efficient, cost-effective and accessible protocols for patients.

The objective of this project is to assess the efficacy and safety of two intensive and spaced protocols (unilateral and bilateral) of 1800 pulses TBS compared to sham stimulation in outpatients with unipolar and bipolar TRD in a public hospital.

This project is the 1st double-blind placebo-controlled RCT with TBS in Spain. It is now in the recruitment phase. Patients receive a total of 22 sessions of 1800 pulses in 6 weeks: 5 days/week the 1st and 2nd weeks (10 sessions) and 3 sessions/week the following weeks (12 sessions). Patients are randomized into three groups: i) bilateral, ii) left unilateral, and iii) sham. The main variable is the change in the HDRS-17 score at the end of treatment compared to baseline. The results were analyzed with a general linear model of HDRS, using time as the intrasubject factor and randomization group as the intersubject factor, using resistance to treatment (Maudsley Score) and diagnosis (bipolar, unipolar) as covariates.

Preliminary results from 13 participants (nbil=4, nuni=4, nsham=5) reveal a significant effect of (group x time) on HDRS change (p= 0.020) with no influence of Maudsley Score or diagnosis. The bilateral group presented a greater decrease in the HDRS with a mean difference of 4,38 points [CI95% 0,17-8,58), (p=0.043)] with respect to the unilateral group and a difference of 8.23 [CI95% 4,24-12,21)(p =0.001)] compared to the sham group.Table 1:Sample description. Data shown are means and standar deviations. In bold significant diferences p<0,05.

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The results demonstrate the preliminary efficacy of intensive TBS protocols relative to sham.

None Declared

Mental health disorder is common among working population worldwide and among health care-workers (HCWs) in particular. Depression is a major public health problem, with an economic impact because of lost days of work. Its prevention is essential and requires the identification of risk factors.

The objectives of this work were to determine the epidemiological characteristics of depressive disorders in health care workers and identify their main risk factors.

A descriptive retrospective study was conducted on health care workers of Sousse in Tunisia who have had a long-term sick leave for depressive disorders from January 2010 to December 2021. data was collected from the medical records of the patients and completed with a telephone questionnaire

The total number of cases was 650 with a prevalence of 12.8% and an incidence of 2 cases per 100 HCW. The median age was 50 years and the female workers represented 81% of cases. The majority of the sample were married (81%). Most of cases were nurses (43%) and health technician (19%). The median seniority of HCW in their jobs was 23 years with the first quartile at 12 and the third quartile at 31.

Around 48% of cases had severe depression. The severity of depression was significantly associated with working in surgical and emergency services, number of night shifts of 2 or more per week, the history of a psychiatric disorder other than depression, habits such as smoking and drinking, anxiety specificity and melancholy specificity of depression.

This study showed the importance of social and occupational factors of depression among HCW. Action policies focusing on workplace interventions appear to be relevant.

None Declared

There is evidence that the concentrations of the main inhibitory neurotransmitter (GABA) may be altered in schizophrenia. The purpose of this study is to find the changes in the GABA concentration in the area of anterior and posterior cingulate cortex of patients with early-stage schizophrenia using the spectral-edited magnetic resonance spectroscopy.

To measure the cerebral concentrations of the gamma-aminobutyric acid in schizophrenia patients at early stage.

Thirty-one subject, 18 controls (11m+7f, 29.6±5.7 y.o.) and 13 schizophrenia patients (F20.0, 8m+5f, 27.5±3.1 y.o.). Philips Achieva dStream 3T MRI scanner, standard head coil. The 3D T1w head images and MEGA-PRESS GABA spectra in ACC and PCC areas were acquired with the following parameters: 50x25x25 mm, TR = 2 s, TE = 64 ms, 180-editing pulses applied at 1.9 ppm and 7.6 ppm, NSA = 288 (acq.time ~10 min). GABA spectra were processed in Gannet program. The intensities of the GABA, Glutamate+glutamine (Glx), creatine (Cr) and unsuppressed water signals were acquired. T-test was used in search for between-group differences.

In ACC region, significant reduction of the GABA/Water was observed (by ~15%, p=0.02) as well as a trend to a decrease in GABA/Cr (by ~10%, p=0.07) in schizophrenia. In PCC, no significant GABA/Water or GABA/Cr differences were observed. Glx/Water and Glx/Cr in both areas were also unchanged.

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This study provides insight into neurotransmitter alterations at early-stage schizophrenia. The results demonstrate the region-specific changes in the balance of the main neurotransmitters. Since this balance is crucial for the normal cerebral functioning, the results may facilitate better understanding of the dynamics of the pathological process and provide additional information for understanding the biological mechanisms of the schizophrenia development.

None Declared

Despite the significant scientific progress in the study of the mechanisms underlying mental disorders, stable biomarkers facilitating their diagnosis and differential diagnosis are lacking. Therefore, we attempted to explore possible functional connectivity (FC) differences across some of the more prevalent mental disorders, namely mood disorders.

The current study aimed at investigating the alterations of the functional connectivity of major seeds of the Salience Network (SN) (the Anterior Cingulate Cortex (ACC), and Anterior Insula (AI) in patients with unipolar (Major Depressive Disorder-MDD) or bipolar (Bipolar Disorder-BD) depression as compared to healthy controls (HC).

For this study 103 adult subjects underwent resting-state Magnetic Resonance Imaging of whom 60 were patients with a depressive episode (MDD: n=35; BD: n=25), and 43 were healthy controls (HC). The individuals in both groups were matched for age and gender. Each participant has provided written informed consent (Ethics Committee: P186/22.01.2021). Seed-to-voxel analysis was performed via the CONN toolbox running on MATLAB. Random Field Theory parametric statistics was used with a cluster-level FWE correction p<0.05.

Both the ACC and the right AI demonstrated a statistically significant increase in the FC to the somatosensory cortex and the motor cortex in patients as opposed to HC. In addition, there was hyperconnectivity between ACC and the right Superior Frontal Gyrus, Precuneus, and the Superior Parietal Lobule bilaterally in patients as well. A reduced FC between the ACC and the hippocampus and parahippocampus was observed in depression in comparison to HC. The analysis of the left AI seed yielded no statistically significant between-group differences.

Our results demonstrate aberrant connectivity between nodes of the SN, the Default Mode Network, and the Limbic Network which might provide clarification on the mechanisms of impaired balance between internally and externally oriented attention, affective and cognitive control in depression. In addition, the alterations of the FC between SN and the somatosensory and motor cortices may be suggested as a possible explanation of the disturbances in the psychomotor activity in mood disorders.

A. Todeva-Radneva Grant / Research support from: This work has been funded by the Bulgarian National Program “European Scientific Networks” - Project DIP Neuroscience, R. Paunova Grant / Research support from: This work has been funded by the Bulgarian National Program “European Scientific Networks” - Project DIP Neuroscience, D. Stoyanov Grant / Research support from: This work has been funded by the Bulgarian National Program “European Scientific Networks” - Project DIP Neuroscience, T. Zdravkova Grant / Research support from: This work has been funded by the Bulgarian National Program “European Scientific Networks” - Project DIP Neuroscience, S. Kandilarova Grant / Research support from: This work has been funded by the Bulgarian National Program “European Scientific Networks” - Project DIP Neuroscience

Prior mechanistic studies in rodents showed decreased levels of the pivotal mitochondrial metabolite acetyl-L-carnitine (LAC) in relation to cognitive deficits and depressive-like behavior (Neuron 2017, 10.1016/j.neuron.2017.09.020, PNAS 2013, 10.1073/pnas.1216100110), providing the basis for the current translational study.

The main objective of this work was to ascertain the role of this specific mitochondrial signaling pathway in subjects with cognitive impairments (CI), and potential sex differences in these mechanisms.

We used computational approaches, ultraperformance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS) and available plasma samples from a well-characterized cohort of 71 subjects, including subjects with CI and age- and sex-matched cognitively healthy controls (HC).

Our newest findings showed decreased levels of LAC in subjects with CI as compared to age- and sex-matched HC. We also found important sex differences in carnitine levels in relation to cognitive function as assessed by using the Mini Mental Status Exam (MMSE). Specifically, the degree of carnitine deficiency reflected the severity of cognitive dysfunction in a sex-specific manner. Using computational approaches, we found that the integration of these mitochondrial measures with canonical biomarkers improves diagnostic accuracy.

The current findings of sex differences in carnitine deficiency in subjects with CI suggest a possible sex-specific mitochondrial phenotype of vulnerability to cognitive dysfunction, and point to LAC-related mitochondrial metabolism as a new signaling pathway of cognitive regulation.

None Declared

Autism is neurodevelopmental disorder with a heterogeneous presentation of symptoms, which include disturbances in sensory, motor and cognitive processes, among which social cognitive impairments and social interaction difficulties play prominent role. Despite the fact that these impairments can lead to lifelong disability and difficulties in everyday functioning, their neurobiological basis remains largely unknown. Neural oscillations in the gamma band have been shown to be an important candidate neurobiological marker of higher order cognitive processes and social interactions. Yet, alterations of gamma oscillations in ASD have received little attention in the literature.

The aim of the current study was to investigate resting state gamma oscillations in the EEG in order to delineate alterations in ASD as compared to typically developing (TD) subjects in the intrinsic activity of the neural networks that have been linked to social cognitive functioning.

Resting-state EEGs were obtained in an ongoing study investigating ASD (N=19) and TD subjects (N=15), based on eyes closed condition. EEGs were recorded using a 128-channel BioSemi system. EEG absolute power was investigated in the gamma 30-48Hz frequency band.

Gamma activity was significantly (p<0.05) diminished in multiple brain regions in ASD as compared TD subjects. The diminished gamma activity had a distinctive topographical distribution, which included the left and right inferior temporal gyrus, the right superior temporal gyrus, the TPJ and the right extrastriate areas. Additionally, we found a hemispheric asymmetry in the occipital brain areas with a decrease of gamma activity on the right and an increase in the left hemisphere as compared to TD.

Diminished gamma activity in the above brain areas may represent a cortical dysfunction which can be present due to a reduced capacity to process socially relevant information and a decreased capacity to omit irrelevant stimuli.

Funding: Hungarian Brain Research program,#NAP2022-I-4/2022

None Declared

Bipolar patients (BP) frequently have cognitive deficits, that impact on prognosis and quality of life. Finding biomarkers for this condition is essential to improve patients’ healthcare. Given the association between cognitive dysfunctions and structural brain abnormalities, we used a machine learning approach to identify patients with cognitive deficits.

The aim of this study was to assess if structural neuroimaging data could identify patients with cognitive impairments in several domains using a machine learning framework.

Diffusion tensor imaging and T1-weighted images of 150 BP were acquired and both grey matter voxel-based morphometry (VBM) and tract-based white matter fractional anisotropy (FA) measures were extracted. Support vector machine (SVM) models were trained through a 10-fold nested cross-validation with subsampling. VBM and FA maps were entered separately and in combination as input features to discriminate BP with and without deficits in six cognitive domains, assessed through the Brief Assessment of Cognition in Schizophrenia.

The best classification performance for each cognitive domain is illustrated in Table 1. FA was the most relevant neuroimaging modality for the prediction of verbal memory, verbal fluency, and executive functions deficits, whereas VBM was more predictive for working memory and motor speed domains.Table 1.Performance of best classification models.

Overall, the tested SVM models showed a good predictive performance. Although only partially, our results suggest that different structural neuroimaging data can predict cognitive deficits in BP with accuracy higher than chance level. Unexpectedly, only for the attention and processing speed domain the best model was obtained combining the structural features. Future research may promote data fusion methods to develop better predictive models.

None Declared

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.

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.

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.

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).

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.

None Declared

N-Methyl-D-aspartate (NMDA) receptors are involved in learning and memory. It is known that ventral hippocampus is a crucial structure involved in emotional memory formation mainly for fear and anxiety situations. The aim of this research is to identify the effect of the stimulation of ventral hipocampal NMDA receptors on the reextinction of an aversive emotional memory task. NMDA (0.2 ug/μl; 0.2 μl) or saline (0.9 %; 0.2 μl) was bilateral and locally administered in the ventral hippocampus of male Wistar rats, before the re-instatement trial.

The experimental group consisted of 10 animals and the control group by 9 subjects. The results suggest that the activation of ventral hipocampal NMDA receptors induces an increase in the time needed to re-extinguish the conditioned fear, suggesting a possible potentiating effect on re-installation.

To evaluate the effect of NMDA at the intrahippocampal level, on the reinstatement and re extinction of a conditioned fear response in male Wistar rats.

This study is experimental, where two groups of adult male Wistar rats were used. The bilateral cannulas was implanted, the animals were injected intraperitoneally with a mixture of ketamine (Rotexmédica) and xylacin (Bayer; 75 mg/Kg and 5 mg/Kg), respectively, then the animals were placed in a stereotaxic apparatus (Narishige) and injected with veterinary antibiotic.The (21G) caliber cannulas were bilaterally implanted in HPv at the following coordinates: AP = -5.2 mm relative to Bregma; ML = ± 5 mm in relation to the midline and DV = 5.1 mm in relation to the skull and according to the atlas (Paxinos & Watson, 1985).

It was observed that in the first phase of extinction there were no statistically significant differences between the two groups, experimental and control, as in the second phase of extinction. The results obtained for the re-extinction phase 1 and 2 showed that there were significant statistical differences between the groups. This difference was only evident in the first three minutes in the two phases of re-extinction.

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Statistically significant differences were observed between the two groups, in the phases of re-extinction, seeing a longer time of the freezing response in the experimental group, as an effect of the application of NMDA in the ventral hippocampus (HPv), which suggests that this substance has a memory-enhancing effect, and therefore contributes to increasing the permanence of the fear response. It should be noted that this difference was only evident in the first three minutes in the two re-extinction phases. These results may be related to other studies where it has been shown that LTP is dependent on the N-methyl-D-aspartate receptor in the CA1 region in vivo (Zhong, Cherry, Bies, Florence, & Gerges, 2009)

None Declared

One of the main obstacles in providing effective treatments for major depressive disorder (MDD) is clinical heterogeneity, whose neurobiological correlates are not clearly defined. A biologically meaningful stratification of depressed patients is needed to promote tailored diagnostic procedures.

Using structural data, we performed an unsupervised clustering to define clinically meaningful clusters of depressed patients.

T1-weighted and diffusion tensor images were obtained from 102 MDD patients. In 64 patients, clinical symptoms, number of stressful life events, severity and exposure to adverse childhood experiences were evaluated using the Beck Depression Inventory (BDI), Schedule of Recent Experiences (SRE), Risky Family Questionnaire (RFQ), and Childhood Trauma Questionnaire (CTQ). Clustering analyses were performed with extracted tract-based fractional anisotropy (TBSS, FSL), cortical thickness, surface area, and regional measures of grey matter volumes (CAT12). Gaussian mixture model was implemented for clustering, considering Support Vector Machine (SVM) as classifier. A 10x2 repeated cross-validation with grid search was performed for hyperparameters tuning and clusters’ stability. The optimal number of clusters was determined by normalized stability, Akaike and Bayesian information criterion. Analyses were adjusted for total intracranial volume, age, and sex. The clinical relevance of the identified clusters was assessed through MANOVA, considering domains of clinical scales as dependent variables and clusters’ labels as fixed factors. Discriminant analysis was subsequently performed to assess the discriminative power of these variables.

Cross-validated clustering approach identified 2 highly stable clusters (normalized stability=0.316, AIC=-80292.48, BIC=351329.16). MANOVA showed a significant between-clusters difference in clinical scales scores (p=0.038). Discriminant analysis distinguished the two clusters with an accuracy of 78.1%, with BDI behavioural and CTQ minimisation/denial domains showing the highest discriminant values (0.325 and 0.313).

Our results defined two biologically informed clusters of MDD patients associated with childhood trauma and specific clinical profiles, which may assist in targeting effective interventions and treatments.

None Declared

Depression is the predominant mood alteration in bipolar disorder (BD), leading to overlapping symptomatology with major depressive disorder (MDD). Consequently, in clinical assessment, almost 60% of BD patients are misdiagnosed as affected by MDD. This calls for the creation of a framework for the differentiation of BD and MDD patients based on reliable biomarkers. Since machine learning (ML) enables to make predictions at the single-subject level, it appears to be particularly suitable for this task.

We implemented a ML pipeline for the differentiation between depressed BD and MDD patients based on structural neuroimaging features.

Diffusion tensor imaging (DTI) and T1-weighted magnetic resonance imaging (MRI) data were acquired for 282 depressed BD (n=180) and MDD (n=102) patients. Axial (AD), radial (RD), mean (MD) diffusivity, and fractional anisotropy (FA) maps were extracted from DTI images, and voxel-based morphometry (VBM) measures were obtained from T1-weighted images. Each feature was entered separately into a 5-fold nested cross-validated ML pipeline differentiating between BD and MDD patients, comprising: confound regression for nuisance variables removal (i.e., age and sex), feature standardization, principal component analysis, and an elastic-net penalized regression. The models underwent 5000 random permutations as a test for significance, and the McNemar’s test was used to assess whether there was any significant difference between the models (significance threshold was set to p<0.05).

The performance of the models and the results of the permutation tests are summarized in Table 1. McNemar’s test showed that the AD-, RD-, MD-, and FA-based models did not differ between each other and were significantly different from the VBM.Table 1.Models’ performance and p-value at 5000 permutation test.

In conclusion, our models differentiated between BD and MDD patients at the single-subject level with good accuracy using structural MRI data. Notably, the models based on white matter integrity measures relying on true information, rather than chance.

None Declared

Inhibition is a core component of executive functions but is not a unitary construct. Instead, different inhibitory processes have specific behavioral effects and neural bases. Three important inhibitory functions explored by the literature are 1) interference control (i.e., inhibition of distractive information); 2) inhibition of prepotent responses and 3) inhibition of ongoing responses. These functions were described in the self-regulation theory as the possible main impairment in attention-deficit hyperactivity disorder (ADHD) and since then they have shown an association with several psychiatric disorders.

The current study investigated the neural bases of interference control, inhibition of prepotent responses, and inhibition of ongoing responses as they were assessed by a Stroop-matching/stop-signal task developed by our group.

The Stroop-matching/stop-signal employs different conditions to create the demands for each inhibition which allows the assessment of these functions using a single protocol. Brain activations were acquired using fNRIS in a block-design method. The concentration of oxygenated hemoglobin (HbO). The first level analysis of HbO signals used a general linear model (GLM) to estimate individual brain activations. The second level analysis was performed using a linear mixed model to generate brain activations at the group level. Alpha level = 0.05 and the false discovery rate was applied when necessary. The sample was composed of 25 young adults (mean age = 21.8, SD = 4.39).

task Interference control showed activation in the left and right temporoparietal junction (TPJ), the right dorsolateral prefrontal cortex (DPLFC), and inferior frontal gyrus (IFG); inhibition of prepotent responses showed increased activity in the right IFG and left DLPFC; the suppression of ongoing responses showed a deactivation of the IFG and DLPFC bilaterally.

These results indicate that the three inhibitory functions assessed present distinct brain patterns of function. The lateralization role was evident in DLPFC and IFG activities and recruitment of parietal areas seems to be limited to interference control in this protocol. Also, the stop-signal demand led to the deactivation of areas associated with the resolution of the primary Stroop-matching task. This study elucidates the role of brain mechanisms associated with specific inhibitory processes that are impaired in psychiatric disorders such as ADHD.

Financial support: FAPESP [grant 2019/20757-5, 2019/21773-4, 2020/14800-2]; CAPES Proex [grant 0426/2021, 23038.006837/2021-73]; Mackpesquisa; CNPq [grant 307443/2019-1]

None Declared

Schizophrenia (SCZ) is one of the most severe mental disorders. Several elements involved in pathogenesis have been characterized recently. However, tools for diagnosis and risk prediction are limited. Elucidation of the underlying genomic and molecular mechanisms of SCA remains a challenge.

In this study, we aimed to identify plasma biomarkers for SCZ using targeted metabolomics.

All enrolled patients were drug-free for at least 3 months prior to admission. Plasma from 31 SCZ patients and 70 matched controls were analyzed using the LC/MS- Api 4000 QTrap Sciex. A total of 188 targeted metabolites, including 21 amino acids, 21 biogenic amines and 145 lipids or lipid-related metabolites were analyzed. All data modeling and analysis is done using MetaboAnalyst 5.0

There was no significant difference in the studied groups regarding BMI. Plasma Triglycerides, LDL-C, total proteins levels were significantly decreased in SCZ compared to controls. Heatmap identified 2 clusters with 25 significantly differentially expressed metabolites (FDR <0.05) between the drug-naïve group and the matched controls. The OPLS-DA score plot showed that the groups are clearly separated according to plasma phospholipids concentrations. Among these differential metabolites, the expression level of very long chain Phosphatidylcholines (PC 36 – PC p42) and acylcarnitines were significantly decreased in SCZ compared to controls, whereas sphingomyelin (SM) and lysoPC were significantly lower in drug-naive patients.

In this study, we found that plasma phospholipids were significantly dysregulated in the SCZ patients and could be a promising pathway to explore SCZ.

None Declared

Postictal psychosis is the most frequent psychosis in epileptic patients, appearing between 3-8% of them. As temporary criteria, it must appear in less than a week after the epileptic crisis, with a duration of between 15 hours and 3 months.

We present the case of an 82-year-old patient admitted to the ED due to an epileptic seizure. Request evaluation for agitation and disorientation.

This is an 82-year-old patient diagnosed with epilepsy for 5 years, with unwitnessed seizures, under treatment with levetirazetam. In the last consultation with neurology, the differential diagnosis was raised with anxiety crises due to normal intercritical EEG.The patient went to the emergency room after a partial crisis, presenting a post-critical state and beginning hours later with disorientation in time and place, manifesting delusions of religious content, as well as visual hallucinations of the same type, presenting agitation that required pharmacological and mechanical restraint.

Admission to the Neurology Service was decided, with a good response to treatment with a typical intramuscular antipsychotic, with complete remission of the condition in 48 hours. Small areas of ischemia compatible with the patient’s age are observed in the cranial CT and the EEG shows slowed global activity.

Postictal psychosis is a phenomenon of low prevalence, however, it is important to take it into account. It is important to recognize the postictal “lucid” period in patients with a family or personal history of psychiatric illness and seizures with compromised consciousness.

None Declared

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.

The aim of the study was to analyze the microstructural and metabolic features of the corpus callosum in recently onset schizophrenia.

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).

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.

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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.

None Declared

Social pain is a phenomenon where you feel pain in response to a social stimulus such as feelings of loss, exclusion, and injustice. In today’s world, people often experience unfair treatment. A special case is a situation in which the individual has aroused commitment, but there is no consequence in the form of the expected gratification.

The study aims to determine the impact of losing and unjust losing on the perception of pain.

The study involved 80 people who were randomly assigned to one of the following groups: win, lose, unfairly lose and control. The first three groups participated in a “paper-scissor-stone” game that was created in which they played against a false opponent. The game was constructed in such a way as to obtain the result provided for each group. The “unfairly lose” group received negative points for both a loss and a draw. The control group was only watching the play of two other players. Pre- and post-game pain thresholds and pain tolerance were tested in each group. Pain severity was also assessed. The pain was generated by a thermal stimulus using the TSA-II neuroanalyzer. Pain severity and involvement in the game were analyzed with the VAS scale.

The level of involvement in the game was identical in all three experimental groups. The lowest pain nuisance was observed after the game in the “win” group. The pain was the most strenuous in the group that was unjustly lost. In the group of “unfairly lose”, the pain tolerance threshold decreased after the game.

Feelings of injustice can increase pain and pain sensitivity in people who, after inducing commitment, do not receive fair gratification.

E. Wojtyna Grant / Research support from: National Science Centre, A. Mucha: None Declared

Psilocybin is a naturally occurring psychedelic compound whose effects have been seen in studies for treatment of depression, anxiety and pain management. Given its structural similarities to 5-hydroxytryptamine, a monoamine controlling brain modulation of pain input, preliminary studies sought to test serotonergic interactions of psilocybin with headaches.

Explore efficacy of psilocybin as treatment for individuals with headaches, including migraines, essential headaches, cluster headaches and unclassified head pains.

Studies were found from six major databases, with inclusion criteria consisting of participants with any type of headache using psilocybin as a treatment. Each study was independently screened by two reviewers at two stages, with inconsistencies reviewed by a third, senior reviewer.

The systematic review evaluated eight articles. Benefits of macrodosing were explored in one study which reported higher levels of pain relief in comparison to microdosing and conventional pain medications. Top benefits of microdosing as reported by participants included convenience, perceived safety and reduced side effects when compared to hallucinogenic doses of psilocybin. Participants across five studies reported improvements to their headaches as characterized by changes in frequency, intensity, duration and remission period. Reported improvements were clinically significant in the six studies and statistically significant in three papers. With psilocybin intervention, two studies reported a decrease in headache attack frequency, three studies reported a decrease in intensity, and one study indicated a decrease in duration. The greatest benefit reported was for psilocybin taken during a remission period, with the average length of that remission period between headaches extending for 91% of participants. One study focused on the dosages of psilocybin in relation to its efficacy, indicating that there was more headache pain relief amongst macrodosers, with a difference of 12.3% of participants experiencing pain reduction 3 days after dosage in comparison to microdosers. 18% of participants who experienced essential headaches also experienced hallucinations as a result of ingested psilocybin. Others showed a temporary increase in symptoms of anxiety and pain - 5.3% with microdosing and 14.1% macrodosing. One study observed an increase in average arterial pressure after ingestion.

Six of eight screened papers showed that psilocybin was clinically significant in the treatment of headaches as captured through self-reports. While the first controlled study for psilocybin use for headaches was detailed in this study, psilocybin remains illegal in many countries, presenting a need for further regulated research.

None Declared