Combatants who are exposed to events which transgress deeply held moral beliefs might face lasting psychopathological outcomes, referred to as Moral Injury (MI). However, knowledge about pre-deployment factors which might moderate the negative consequences of MI is sparse.

In this prospective study, we examined pre-enlistment characteristics and pre-deployment personality factors as possible moderators in the link between exposure to potentially morally injurious events (PMIEs) and psychiatric symptomatology among Israeli active-duty combatants.

A sample of 335 active-duty Israeli combatants participated in a 2.5-year prospective study with three waves of measurements (T1: 12 months before enlistment, T2: 6 months following enlistment- pre deployment, and T3: 18 months following enlistment- post deployment). Participants’ characteristics were assessed via semi-structured interviews (T1) and validated self-report measures of personality factors: emotional regulation, impulsivity, and aggression (T2) and combat exposure, PMIEs, psychiatric symptomology and post traumatic symptoms (T3) between 2019-2021.

Pre-enlistment psychiatric difficulties and negative life events contributed to higher exposure to PMIEs post deployment. Higher levels of pre-deployment aggression and lower levels of emotional regulation and impulsivity moderated the association between betrayal, PMIEs and psychiatric symptomology post deployment, above and beyond pre-enlistment psychiatric difficulties and life events.

Our results highlight that pre-deployment emotional regulation, impulsivity and aggressiveness levels should be assessed, screened, and identified among combatants, as they all facilitate psychiatric symptomology (and PTSS) after combatants are exposed to PMIEs of betrayal. Such pre-assessment will enable identification of at-risk combatants and might provide them with tailor made preparation regarding moral and ethical situations that should be investigated in future researches.

Y. Levi-Belz: None Declared, G. Zerach Shareolder of: no, Grant / Research support from: no, Consultant of: no, Employee of: no, Paid Instructor of: no, Speakers bureau of: no

It remains debated in the scientific literature whether cannabis aggravates psychotic symptoms or is used as a self-medication. Regular cannabis use (RCU) was found associated with the severity of positive symptoms of psychosis i.e., delusion or hallucinations. However, the association with negative symptoms, i.e. blunted affect or social withdrawal, is less straightforward. Confounding variables such as the criteria for other Substance Use Disorders (SUDs), illness duration, or socio-demographic features can interfere with the appraisal of effect of RCU on these symptoms. Studies are rarely adjusted for these variables and no adjustment can be performed in meta-analyses which use aggregated data. For these reasons, we decided to conduct a mega-analysis based on individual patient data (IPD) allowing to control for theses variables and isolate the specific association between RCU and the severity of symptoms.

Investigate the association between RCU on the positive, negative, general, and disorganized symptoms of psychosis as assessed by the Positive and Negative Syndrome Scale (PANSS), accounting for individual-level confounding variables.

IPD were requested by email to corresponding authors of published articles that measured RCU and PANSS scores in subjects with schizophrenia-spectrum disorders, based on a screening process on PubMed, ScienceDirect and PsycINFO databases. A two-stage random effect multivariate IPD meta-analysis was then performed, to isolate the direct association between RCU and the ‘positive’, ‘negative’, and ‘general’ dimensions of schizophrenia-spectrum disorders. Confounding variables were included in the models when available in the original dataset.

65 publications were eligible for inclusion. 18 authors agreed to provide their IPD. A total of 16 datasets were usable, regrouping 3,346 individual participant data, with 2,827 complete cases. Regression coefficients extracted after the first stage were adjusted for at least sex and age across all studies. RCU was found to be significantly associated with heightened positive symptoms severity (MD = 0.41, 95% CI [0.0; 0.82], p = 0.04), whereas it appeared significantly associated with less severe negative symptoms (MD = -0.63, 95% CI [-1.1; -0.17], p = 0.008). No significant association was found between RCU and general symptoms (MD = -0.24, 95% CI [-069; 0.21]; p = 0.29), as well as disorganization (MD = -0.08, 05%CI [-0.47; 0.35], p = 0.63).

Our results allow for a general and subtle overview of the association of RCU with symptoms of psychosis. Our findings suggest a double and paradoxical effect of cannabis, which could both exacerbate positive symptoms and alleviate negative symptoms. This supports both the hypotheses of a disease aggravator and self-medication.

Results change as we receive datasets from collaborating authors and could continue to change as not all authors sent their datasets yet.

None Declared

Immunological mechanisms may contribute to the causation of mental illness. Autoimmunity is most convincingly shown for anti-NMDA-R encephalitis and Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS); disorders that overlap clinically with schizophrenia and OCD. Altered inflammatory cytokine production, glial activation and auto-antibodies have also been associated with schizophrenia and OCD. In these disorders, however, the treatment results with anti-inflammatory or immunomodulating drugs have hitherto been limited and inconsistent. Yet other targets within the immune system may still be effective and new options are warranted for treatment-resistant patients. Rituximab targets B-lymphocytes and is often used in autoimmune disorders such as rheumatoid arthritis, multiple sclerosis and anti-NMDA-R encephalitis.

We aimed to investigate whether rituximab is clinically effective, safe and tolerable as add-on therapy in markedly ill, treatment-resistant adult psychiatric patients with schizophrenia or OCD. We also wanted to identify putative mediating mechanisms in treatment responders, such as cytokine changes and functional connectivity (FC).

In an open pilot study, adults (18-39 years) with treatment-resistant schizophrenia and/or OCD were included. They received an intravenous infusion of rituximab 1000 mg, once at baseline, in addition to their regular psychiatric medication and were followed for 1 year. The main outcome measures were the Positive and Negative Syndrome Scale (PANSS) or Yale-Brown Obsessive Compulsive Scale (Y-BOCS), the Clinical Global Impression-Improvement scale (CGI-I) and the Personal and Social Performance scale (PSP). Treatment response was defined as ≥ 40 % decrease in PANSS or ≥ 35 % decrease in Y-BOCS, and much improved according to CGI-I. Resting-state fMRI was applied at baseline and after 5 months. Plasma cytokines were measured at 0, 3 and 5 months. Cognitive tests and the recently developed PsychoNeuroinflammatory Related Signs and Symptoms Inventory (PNISSI) were used to identify and measure symptoms related to neuro-inflammation and cognitive function.

Nineteen patients were treated with rituximab. 3-5 months after treatment, 6/9 patients with schizophrenia and 1/10 with OCD responded. One schizophrenia patient continues with rituximab every 6 months and has reportedly done well for almost 3 years. No severe side effects were reported apart from recurrent abdominal pain in a schizophrenia patient and one case of post-COVID-19 syndrome. Significant changes of FC were detected in responders only and correlated with PSP changes.

Aberrant B-cell activities may contribute to treatment-resistant schizophrenia and be amenable to treatment with rituximab. However, the results of this pilot study need confirmation in placebo-controlled trials.

None Declared

Intentionally harming oneself with deliberate destruction of body parts without a suicidal purpose is defined as self-mutilative behavior. Genital Self-Mutilation is an extreme form of such action and usually seen as a result of an underlying psychiatric condition. Although schizophrenia spectrum disorders are the leading cause, substance use, personality disorders, and gender dysphoria may also result in GSM. Klingsor Syndrome, a rare clinical entity, was first described as GSM with religious delusions. Later, Schweitzer proposed expanding the term to include all psychotic disorders. (Veeder et al., Gen Hosp Psychiatry 2017;44:43-50)

The aim of this piece is to report our case of a patient with psychosis performing genital self-mutilation in order to promote proper diagnosis and management of patients with similar conditions.

A 24-year-old male was brought to the psychiatric emergency unit after self-harming behavior causing numerous wounds throughout his face, trunk, and genital area. Penile and scrotal lacerations were prominent. The patient stated that he had inflicted these wounds upon command hallucinations. Examination also revealed disorganized speech, dysphoric mood, paranoid delusions. The wounds were healed and the patient was prescribed antibiotic medication. He was then admitted to the psychiatric ward. The patient’s first psychiatric visit was dating back to four years prior to his inpatient admission. However, symptoms of paranoid delusions and auditory hallucinations had been more severe for about a year. Throughout his outpatient appointments during this time, olanzapine and aripiprazole were tried and a partial response was elicited but the patient generally was non-compliant with the treatment. Cannabis use history was also significant. On admission, the patient was put on amisulpride 800 mg daily, gradually increased to 1200 mg. Valproic acid 1000 mg/day was also added to the treatment in order to control impulsive behaviors. Care of the genital wounds was provided as per the recommendations of the urology department. Near total improvement of the psychiatric symptoms were achieved during the hospitalization. The final diagnosis of Klingsor Syndrome was concluded as the patient was discharged.

The patient’s remission sustained during outpatient follow-ups. About a year after discharge, asymptomatic prolactinemia was detected and managed by reducing amisulpride dose and addition of aripiprazole 5 mg/day.

GSM is a dramatic form of self-harm. The severity of psychotic illness of patients often facilitates the conduction of such behaviors. Appropriate antipsychotic treatment and effective care may prevent patients from inflicting severe damage to themselves. Also, In cases of GSM in patients with underlying psychiatric conditions, an interdisciplinary approach is required.

None Declared

The evidence on the course of the intelligence quotient (IQ) at the long term in individuals with schizophrenia spectrums disorders is inconclusive.

We aimed to analyse whether IQ improves, declines, or remains stable over 10 years in a sample of patients with First Episode Psychosis (FEP) and healthy controls (HCs).

The FEP patients participated in a Program of First Episode Psychosis in Spain called PAFIP. At baseline, FEP patients provided demographic and clinical data, and completed a neuropsychological assessment that included an estimation of premorbid IQ trough the WAIS vocabulary subtest. At 10-year follow-up, the participants were invited to complete the same evaluation and 10-year IQ was estimated. The group of HCs underwent the same neuropsychological battery at both moments. Cluster analysis was performed separately in the FEP patients and the HCs to determine their profiles of intellectual change.

FEP patients (n=137) were grouped into five clusters (see Figure 1): “Improved low IQ” (9.49% of patients), “Improved average IQ” (14.6%), “Preserved low IQ” (17.52%), “Preserved average IQ” (43.06%), and “Preserved high IQ” (15.33%). Ninety HCs were grouped into three clusters: “Preserved low IQ” (32.22% of the HC), “Preserved average IQ” (44.44%), and “Preserved high IQ” (23.33%). Demographic data of FEP patients are presented in Table 1.Table 1.Sociodemographic data of FEP patients

The FEP patients showed intellectual improvement or stability, but no decline post-onset of psychosis. However, their profiles of intellectual change are more heterogeneous than that of HCs over 10 years. Particularly, there is a subgroup of FEP patients with a significant potential for long-term cognitive enhancement.

None Declared

A wide variety of traits is heritable and has genetic loading, including schizophrenia spectrum disorders (SSDs) and its associated neurocognitive features. The genetic architecture of SSDs is polygenic, with the contribution of thousands of single nucleotide polymorphisms of small effect with an estimated SNP-heritability of 24%. The same occurs with neurocognitive phenotypes such as intelligence or educational attainment. Therefore, the method of polygenic risk scores (PRS) is useful in estimating the genetic burden of such traits. Moreover, the use of PRS in a sample of genetically related individuals would allow analyzing the contribution of genetic and environmental factors involved in the development of the disorder and its candidate endophenotypes.

To estimate PRS for schizophrenia, and polygenic scores for intelligence and educational attainment in patients with First Episode Psychosis (FEP), their first-degree relatives (siblings and parents), and a group of healthy controls.

The sample is comprised of 579 participants of the PAFIP-FAMILIAS project in Santander, Spain (133 FEP patients, their 244 first-degree relatives, and 202 healthy controls). All provided sociodemographic information and completed the same neuropsychological battery. Participants’ DNA was extracted from venous blood samples, and genotyping was performed at the Centro Nacional de Investigaciones Oncológicas (CeGen) by the Global Screening Array v.3.0 panel (Illumina). Data quality control, imputation, calculation of PRS, and genetic association analysis are being performed using PLINK, SHAPEIT, IMPUTE2, SPSS and R.

Data analysis is currently in progress, at the quality analysis stage, in collaboration with the Institute of Psychiatric Phenomics and Genomics (IPPG) in Munich, Germany. We expect to find higher PRS for schizophrenia in FEP patients, while their first-degree relatives will potentially show intermediate risk scores between patients and healthy controls. A similar finding is expected regarding intelligence and educational attainment, as FEP patients may show more genetic burden for low intelligence and education.

The estimation of PRS has demonstrated to be valuable in studying complex traits such as schizophrenia. We believe that by applying this method in a family design can provide interesting insights on the development of SSDs and its potential endophenotypes, and potentially useful in their prevention.

None Declared

Text analysis can significantly enrich ideas about the functioning of the psyche in mental illness.

The purpose of this study was to identify the linguistic features of texts written by people with schizophrenia spectrum disorders and to study the relationship between them and the personality traits and indicators of the standard of living of patients.

Twenty-nine patients with schizophrenia spectrum disorders (F20, F21, F23, F25 according to ICD-10) and 37 without mental disorders participated. All participants wrote a text on a given topic and filled in psychodiagnostic methods: a short version of the Big Five method (TIPI-RU), Q-Les-Q, and MOS SF-36. The text was analyzed using the phpMorphy morphological analysis library.

A comparative analysis showed that in the speech of patients, there are fewer adjectives and more verbs than in the speech of healthy subjects (p<0.05) and that the volume of speech production in patients is significantly reduced (<0.001). The results of correlations of such data with the volume of words were contradictory. A statistically significant inverse relationship was found between the verbality index and the factors of extraversion and openness to experience in the clinical group. As for the indicators of quality of life, expectedly positive correlations between the use of adjectives and negative correlations of the use of verbs with the quality of life were revealed.

Studying the linguistic features of the speech of patients with mental disorders is essential. These indicators can be helpful in the diagnosis and treatment of the disease.

None Declared

Despite the critical role of motivation in psychosocial treatment and rehabilitation, as well as functional outcomes in schizophrenia, service user voices are not always present in setting research agendas on this topic. This is important since the service user’s involvement in the research process helps prioritize research questions (Wykes et al., 2015).

We have begun a consultation process to bridge the gap between research and practice on ‘motivation in schizophrenia.’ The study’s main objective was to produce the means to increase motivation in schizophrenia from the perspective of users.

In the current study, we asked the service users about the priorities for ‘motivation and schizophrenia’ research and also suggested involving service users in research itself as partners. Expert Panels with peer leaders previously involved in psychosocial rehabilitation programs took place. A total of 12 Panels (group meetings) were held during the year with three users (schizophrenia spectrum outpatients) aged 45, 47, and 50, male. The reports were analysed using content analysis to generate main themes and findings (Braun & Clarke, 2006).

The users’ elements of motivation may differ from organizationally defined ones; this may be related to different opinions and ethical standards among clinicians on patients’ autonomy and right to refuse treatment. A discussion of the topics patients have developed to improve the motivation, engagement, and management of patients with schizophrenia in psychosocial treatment and rehabilitation is presented.

The approach successfully generated items for questionnaires that usesr participants declared with a sence of pride in and ownership of. It is, therefore, possible to create measures of motivation that users feel reflect their understanding and experiences. The outcome of this research is that other Russian researchers will be inspired to follow the same patrnership path and encourage service users to participate rather than be subjected to research.

None Declared

Antipsychotic drugs are widely prescribed for schizophrenia and other mental disorders. They are critical in the pharmacological management of severe psychotic disorder.

The adverse effects of antipsychotics are common, with a potential negative impact on adherence and engagement. Despite this, the scientific study of the prevalence of adverse antipsychotic effects is a neglected area.

We aim to identify the prevalence of nine clinically important categories of antipsychotic adverse effects, namely: extrapyramidal symptoms; sedation; weight gain; type II diabetes; hyperprolactinaemia; metabolic syndrome, dyslipidaemia; sexual dysfunction; and cardiovascular effects

This is a prospective, observational, cross-sectional study, carried out in Ar-razi hospital in Salé evaluating side effects in patients hospitalized and treated with antipsychotics within 3 months.

In total, antipsychotic polypharmacy was associated with increased frequency of adverse effects, and a longer duration of treatment is associated with greater severity; clozapine was more strongly associated with metabolic disturbance than other antipsychotics in three studies and olanzapine was associated with the most weight gain in three studies; hyperprolactinemia was more common in women than men, but more men noted sexual dysfunction than women;

Antipsychotic adverse effects are diverse and frequently experienced, but are not often systematically assessed. There is a need for further scientific study concerning the management of these side effects.

None Declared

Developmental predisposition to schizophrenia can be a consequence of early experienced traumas. Transgenerational trauma is process in which traumatic experience of one generation is passed on to the next generation.

To show connection between transgenerational transmission of trauma and development of schizophrenia.

Psychiatric interview, psychological testing.

Patient G.E. age 29, admitted to Psychiatry Clinic due to altered behavior, aggressiveness and presence of delusions and hallucinations. First mental problems in form of a catatonic stupor appeared 6 years ago. Patient has history of earlier abuse of psychoactive substances. A drug test performed at admission was negative. Patient was born in Srebrenica in 1993, he escaped to Tuzla with his mother in July 1995, while father survived escaping on foot. Patient is a first child from his father’s second marriage. The father’s first wife and two minor children were shot by Bosnian Serbs in early 1992. Patient was born a year and a half after death of his siblings and was named after his half-sister. Patient’s father consumed alcohol after the war and was aggressive towards children. In the last two years, patient had frequent hallucinations, he told his parents that voices were telling him to kill his mother and told his father that his children were still alive. Diagnostic processing was performed and diagnosis of schizophrenia was stated. During hospitalization, patient was treated with olanzapine and low doses of haloperidol, along with haloperidol decanoate, which resulted in significant reduction of productive psychotic symptoms. A partial remission is achieved, negative schizophrenic symptoms and cognitive impairments verified by psychological instruments remain.

Case report emphasize transgenerational transmission of trauma: father‘s untreated trauma, alcohol dependency and abuse of the patient in childhood. These findings are important for treatment and therapeutic considerations. Mentalizing is a possible mediator between childhood abuse and negative symptoms. Parental bonding was explored within high expressed emotions theory as a risk factor for relapse to psychosis, especially the “affectionless control” in the parental (mainly father‘s) bonding style. Studies also stated that psychotic patients often show insecure attachment representations. Possible pathway for further analysis could be discussed: a cold parental bonding style leading to experienced emotional neglect and attachment avoidance might be reflected in lower capacity to mentalize. To improve the mentalization capacity, it would be essential to establish a sustainable therapeutic treatment frame.

None Declared

The goal of psychotic disorders has led researchers to focus on early identification of individuals at clinical high risk (CHR) for psychosis and treatment of CHR symptoms. CHR symptoms typically occur in adolescence and young adulthood. This is a very sensitive developmental period, and CHR-state is associated with increased functional impairment. Age-appropriate treatment approaches that address youth-specific interests, complex symptomatology, associated distress, and functional impairment are needed. However, there is a lack of research on treatment strategies for this vulnerable age group. To address this gap, we developed the combined treatment program “Robin” (standardized manual and smartphone app). The treatment program targets CHR symptoms, comorbid symptoms, and improvement of quality of life and daily functioning. The smartphone app “Robin Z” is an add-on treatment tool to support patients between their sessions. While a number of studies using smartphone apps in therapy have shown promising effects with adult psychosis patients, little is known about their use in therapy with minor patients. “Robin Z” is one of the first smartphone apps targeting adolescent patients with CHR or full-blown psychotic symptoms.

The investigation of efficacy of this specific intervention versus treatment as usual

Our study was designed as a naturalistic clinical intervention study with a matched controlled design (treatment as usual). A total of 40 help-seeking adolescents (67% female) with CHR symptoms aged 13-18 years (mean age 15.86) were recruited to the intervention condition between September 2017 and May 2022. For the control group, data from 62 patients from a previous study are available and will be matched for age and gender. CHR symptoms, comorbid symptoms, functioning, self-efficacy, and quality of life will be monitored at six time points (baseline, during the treatment phase, immediately after the intervention, and 6, 12, and 24 months later).

All participants have now completed the intervention phase. In Paris, the first results on treatment effects will be presented at the symposium. This will include baseline data for the intervention group and their intraindividual changes in symptomatology, well-being, and level of functioning during and immediately after treatment. In addition, the results of the first follow up examinations compared to the control group will be presented.

To our knowledge, this is the first controlled trial to evaluate the effectiveness of a specific treatment for adolescents with early psychosis combined with a smartphone app. The results of our evaluation are of clinical importance and should provide essential information for both the field of eMental Health and the topic of early intervention in psychosis.

None Declared

Plasma zonulin is acknowledged to be a biomarker for intestinal permeability. Previous studies have demonstrated significant relationships regarding potential effects of zonulin in several major psychiatric conditions including attention deficit and hyperactivity disorder, autism spectrum disorder and depression, however its role in schizophrenia still remains unclear.

We aimed to identify the alterations of plasma zonulin levels between the different periods of the illness and we strive to reveal the associations between plasma zonulin levels and symptoms in patients with chronic schizophrenia.

30 patients with schizophrenia and 29 healthy controls participated in the study. Sociodemographic data form and Positive and Negative Syndrome Scale (PANSS) were administered. Blood sampling was performed for patients who are in exacerbation and following treatment response periods along with the healthy controls. ELISA method was utilized to measure plasma zonulin levels.

The groups did not differ in plasma zonulin level comparisons. Plasma zonulin did not fluctuate between the symptom exacerbation and treatment response periods of the patients. Besides, plasma zonulin level was found to be associated with passive/apathetic social withdrawal, active social avoidance, and somatic concern items of the PANSS in a negative direction.

This is the first follow-up study in the literature that assesses plasma zonulin in patients with schizophrenia. The measurement of plasma zonulin may not be a convenient parameter in distinguishing symptom exacerbation and treatment response periods in chronic schizophrenia, nevertheless it may have implications on reduced social interaction and somatic symptoms. Our study can provide better insight for future studies to be more cautious while interpreting the associations of plasma zonulin levels with psychiatric disorders.

None Declared

The presence of perceptual disturbances and psychotic symptoms associated with substance abuse are widely known. While the abuse of substances is becoming more widespread, there is a general perception that their use entails fewer risks. 25I-NBOMe is a recently introduced hallucinogenic drug producing visual hallucinations and euphoria. Although people consume it like LSD, its chemical structure is different to LSD. 25I-NBOMe is related to other phenylethylamine derivatives (amphetamines and mescaline).

Present a clinical case of psychosis triggered after the consumption of new emerging drugs and highlight that the extension of their consumption in the general population, especially in the most vulnerable, can trigger prolonged psychotic symptoms.

We present a clinical case report of a subject who developed perceptual disturbances and paranoid symptoms. These lasted for months.

We describe the case of a 30-year-old man who required psychiatric admission after a single NBOMe intake five months earlier. He began with self-referential experiences and delusional ideas of prejudice, persecution and control in social networks. For months, intrusive images appeared in the form of flashbacks. He remains isolated, hardly sleeps and is easily irritated. He previously worked and had a well social network. Since adolescence, he had occasionally used alcohol, cannabis and cocaine. An uncle was diagnosed with schizophrenia. Treatment with long-term injectable aripiprazole started, reducing the symptoms and managing to recover work activity in a year.

25I-NBOMe has its main activity as 5HT2 receptor agonism, which is associated with increased dopaminergic activity in the brain. Hallucinations, delusions, anxiety symptoms and depersonalization appear during acute consumption. However, some patients have developed a persistent hallucinatory chronic syndrome after consumption. As its use is expanding, it probably could increase the number of patients with induced chronic psychoses, especially those with greater susceptibility. One of the possible causes would be its analogous structure to other derivatives of phenylethylamine, which increase the risk of psychosis, and another would be the erroneous perception of being a less dangerous drug.

None Declared

Schizophrenia is a severe mental disorder characterized by negative (e.g., social withdrawal, apathy, anhedonia) and positive (e.g., hallucinations, delusions, disorganized behaviour) symptoms. Schizophrenia prodromal symptoms typically emerge during the adolescence. These symptoms consist of attenuated and/or intermittent psychotic symptoms and define the ultra-high risk (UHR) states of schizophrenia. Approximately, 30% of UHR individuals develop schizophrenia. It is important to find biomarkers associated with the conversion of schizophrenia in UHR individuals in order to develop preventive and therapeutic strategies, as well as to gain knowledge in the ethiopathology of the disorder. In this regard, epigenetic variations have been identified as potential biomarkers associated with the conversion to schizophrenia, but the lack of research prevent to draw final conclusions.

The objective of this communication is to report the study protocol of the research project named “Epigenetic variations associated with the conversion of schizophrenia in ultra-high risk adolescents”. Its aim is to analyze the epigenetic marks that predict the development of schizophrenia in UHR youths.

A 4-year observational follow-up study will be conducted, assessing three groups of adolescents who have sought clinical hep: 1) UHR group composed of individuals who have developed schizophrenia at the end of the follow-up; 2) UHR group composed of individuals who did not develop schizophrenia at the end of the follow-up; 3) a group composed of non-UHR individuals. Epigenetic marks will be analyzed in the peripheral blood of all the participants each 6 months. Clinical (i.e., positive and negative symptoms, depressive symptoms, anxiety symptoms, global functioning, traumatic events, alcohol and other toxics consumption) and sociodemographic data (i.e., age, sex, migration status, ethnicity, socio-cultural status, academic achievements) will be also assessed through standardized questionnaires.

We hypothesize that specific epigenetic marks will predict the conversion of schizophrenia in the UHR group. Moreover, interactions between epigenetic variations and sociodemographic data will differentiate the three groups after the follow-up.

The findings of this project will help to develop preventive and therapeutic strategies, as well as to gain knowledge in the etiopathological pathways of schizophrenia.

None Declared

Schizophrenia is a chronic psychiatric illness with symptoms in positive, negative and cognitive domain.The interplay of dietary folic acid intake with common genetic variants that influence folate metabolism, has potential implications for Schizophrenia pathogenesis and treatment.Therefore, it’s deficiency has been identified as a risk factor for Schizophrenia through epidemiologic, biochemical and gene association studies.

1-To assess the efficacy of folic acid supplementation on severity of symptoms and overall functional status of patients

2-To assess the correlation of serum folate levels with symptom severity and overall functional status of patients

A randomized control trial study was carried out in the inpatient department of a psychiatric tertiary care centre on 40 participants (29 males and 11 females)who were between the ages of 18 – 55 years,met diagnostic criteria for Schizophrenia (ICD 10) and had at least 2 years of illness duration while those with a co-morbid psychiatric illness, medical illness and substance abuse were excluded. The participants were then randomly allocated into two groups (experimental Group A which received 5mg folic/day along with anti psychotic drugs and control Group B which received only anti psychotic drugs) and followed up for 3 months. Blood sample for measuring serum folate level was obtained from the experimental group at the beginning and at the end of the study period. Scales applied were Positive and Negative Syndrome Scale(PANSS) for symptom severity and Global Assessment of Functioning scale(GAF) for overall functional status.

A significant difference (p value< 0.05) was observed in PANSS scores at the end of the study between experimental group and control group( table 1) and also in GAF scores between both the groups after 3 months(table 2). At the end of the study period,a strong negative correlation(r= -0.9) was found between serum folate level and total PANSS score in the experimental group (figure 1) while the correlation between GAF score and serum folate level was strongly positive (r= 0.8) (figure 2).Table 1

Image:

Image 2:

Our study is among the few to use a randomized controlled study design for assessing the effect of folic acid supplementation on severity of symptoms and global functioning in Schizophrenia,strongly suggesting the use of folic acid as an adjuvant treatment for Schizophrenia.

None Declared

Psychotic disorders carry several economical, psychological and social consequences, both at individual and community levels. Early intervention programs after first-episode psychosis which combine pharmacological and psychosocial strategies are aimed at reducing symptoms, lowering costs in the use of health and non-health care resources and improving overall functioning. AGES-Mind study is based on manualized psychotherapeutic interventions for people with first-psychosis episodes.

The aim of the study was to evaluate the effect of a group psychotherapeutic intervention on the clinical status and use of clinical resources in a sample of patients with first-episode psychosis at 12 and 24 months after the beginning of the intervention. This cohort will be compared to patients with first-psychosis episodes without group psychotherapeutic intervention.

Longitudinal, observational, retrospective study on a cohort of N=46 patients with first-episode psychosis within the last 5 years. Two groups of 23 patients each were formed. The participants of one of those groups received group psychotherapy in the context of the AGES-Mind study and the other group received treatment as usual without group intervention. Non-exposed patients were matched by age, gender and time elapsed since first-episode psychosis with those exposed to the intervention. Sociodemographic data, clinical status and use of clinical resources outcome variables were assessed.

No significant differences were found in clinical status and use of resources between participants and non-participants in the psychotherapeutic group intervention after 12 and 24 months.

After controlling for potentially confounding variables as sociodemographic, age and time since first-episode, participating in a group psychotherapeutic program does not seem to improve clinical variables or use of resources. Further studies with larger samples would be necessary to explore other variables, such as symptoms, satisfaction with the intervention or social functioning.

None Declared

Cycloid psychosis is a clinical entity with defining traits which emerged from the Wernicke-Kleist-Leonhard school of psychiatry and has a long history in Europe. Leonhard distinguished three clinical forms: anxiety-happiness, confusion and motility psychosis. It is a condition with high clinical heterogeneity and favorable prognosis.

To describe a case of cycloid psychosis and review in literature the heterogeneity of this phenomena and its clinical management.

Clinical case report and brief review of literature.

57-year old male with previous diagnosis of paranoid schizophrenia and severe congenital hearing loss. Preserved autonomy and adequate real-life and interpersonal functioning. Along the past few years the patient has presented episodes of a significant clinical global worsening in context of mainly somatic symptoms (intestinal obstruction and volvulus) and minor stressful life events. On this occasion he appears in the emergency room with a new episode of abdominal pain and is admitted to Internal Medicine with presumptive diagnosis of intestinal volvulus. The patient gathered heterogeneous symptoms including disorientation, confusion, generalized tremor, gait disorder, profuse sweating, regressive and oppositional behaviors (refusal to eat or drink liquids) and sudden behavioral oscillations (from agitation to prostration). From the psychic point of view he showed thought blocking, mutism, significant anxiety, fear of death, delusional prejudice ideas and sensoperceptive disturbance which seemed otherwise related to previous sensorial problems. We introduced treatment with Olanzapine 30 mg and after 4 weeks, the patient suddenly showed a significant clinical improvement until the complete remission of the symptoms and restitution of his previous state. In coordination with his regular psychiatrist was proposed the controversial diagnosis of cycloid psychosis. Cycloid psychosis gather a few clinical features which differentiate it from other entities: acute onset, polymorphic symptomatology, global disturbance of psychic life, remitting and recurrent course and favorable prognosis. Regarding its clinical management no controlled studies have been conducted to this date of the treatment of this phenomena. According to literature ECT seems to be an effective treatment as well as low-doses of atypical antipsychotics. Some authors propose pharmacological maintenance treatment with mood stabilizers.

The diagnosis of cycloid psychosis can be useful as well as necessary to describe certain patients with similar clinical features, recurrent course and favorable prognosis. Future studies on pharmacological approach would be useful to ensure the appropriate clinical management of these patients.

None Declared

Schizophrenia (SCH) and bipolar disorder (BD) are severe mental disordes, which have high incidence (Whiteford et al. Lancet 2013; 381 1575-86) and are the main causes of diasibility in young people (WHO 2022; https://www.who.int/news-room/fact-sheets/detail/mental-disorders).

Psycological stress appears in different mental disorders, and this is directly related to oxidative stress (Moller et al. Chem Biol Interact. 1996; 102 17-36)(Pupic-Bakrac et al. 2020; Psychiatr Danub. 32 412-9). Oxidative stress causes reticulum edoplasmic stress (ER stress) and this produces high levels of misfolded proteins. Defective proteins are degraded by the proteasome, but but when the density of misfolded proteins exceeds the capacity of the proteosome, the Unfolded and Misfolded Protein Response (UPR) is triggered through three main pathways: Inositol-requiring enzyme 1α (IRE1α); transcription factor 6 alpha (ATF6α) and protein kinase RNA-Like ER kinase (PERK), trying to recover normal protein synthesis capacity (Bermejo-Millo et al. 2018; Mol Neurobiol. 55 7973-86) (González-Blanco et al. 2022; J Cachexia Sarcopenia Muscle 13 919-31).

Characterizing ER stress and UPR in SCH and BD.

We studied ER stress and UPR in peripheral blood mononuclear cells (PBMC) from 50 patients with SCH and an equal number of patients with BD compared to their corresponding controls in order to achieve our objectives.

Western Blot assay were performed following classical procedure () and the results was normalized to Ponceau as loanding control (Nie et al. 2017; BiochemByophys Resp 12 10-13) (Sander et al. 2019; Anal Biochem 575 44-53). Proteasome activity was assessed using Proteasome Activity Assay Kit (ab107921, Abcam, Cambridge, UK).

ER stress was evaluated with BiP/GRP78. Our results showed significantly increased expression in SCH (p<0,01) and BD (p<0,05), being more increased in SCH. Proteasome activity was increased in SCH and BD, being only statistically significant in SQZ (p<0,05). UPR study showed IRE1a cascade significantly activated in SCH (p<0,001) and only slight increased in BD showed without statistical differences. ATF6a pathway is measured by cleavage to active protein (50-kDa). Results showed higher expression in SCH than in BD and controls (p<0,001). In addition, PERK pathway showed higher statistical levels of p-eIF2a/eiF2a ratio in SCH than in BD and control respectively (p<0,05 and p<0,01).

Our results showed a greater alteration in SCH than in BD at the level of protein synthesis, which implies a greater toxicity at the cellular level and, therefore, a clear risk for the survival of cells in this pathology.

None Declared

Cognitive impairment (CI) is a major determinant of poor functional outcome in schizophrenia and there are currently no available pharmacotherapies. Deficits in glutamatergic signalling play a key role in the neuropathology of cognitive symptoms. Iclepertin (BI 425809), an inhibitor of glycine transporter-1, enhances glutamatergic signalling by increasing synaptic levels of the N-methyl-D-aspartate receptor co-agonist, glycine. A 12-wk, Phase II trial (NCT02832037) in 509 patients (pts) with schizophrenia demonstrated that iclepertin was well tolerated and significantly improved cognition.

The Phase III CONNEX programme aims to confirm the efficacy, safety and tolerability of iclepertin in improving cognition and functioning in a larger cohort of pts.

CONNEX consists of three replicate randomised, double-blind, placebo-controlled parallel-group trials in pts with schizophrenia (NCT04846868, NCT04846881, NCT04860830) currently stable on antipsychotic treatment. Each trial aims to recruit ~586 pts, 18–50 years old, treated with 1–2 antipsychotic medications (≥12 wks on current drug; ≥35 days on current dose prior to treatment), who have functional impairment in day-to-day activities and interact ≥1 hr per wk with a designated study partner. Pts with CI due to developmental, neurological or other disorders, or receiving cognitive remediation therapy within 12 wks prior to screening, will be excluded. Pts will be recruited from 39 countries in Asia, Australia, New Zealand, North and South America and Europe, and randomised 1:1 to receive either oral iclepertin 10 mg (n=293) or placebo (n=293) once daily over 26 wks. The primary efficacy endpoint is change from baseline (CfB) in the MATRICS Consensus Cognitive Battery overall composite T-score. Key secondary efficacy endpoints are CfB in Schizophrenia Cognition Rating Scale total score and CfB in the adjusted total time in the Virtual Reality Functional Capacity Assessment Tool. Long-term safety and tolerability data will be collected in an open-label safety extension study (CONNEX-X).

The studies are currently recruiting (first pts enrolled Aug–Sept 2021), with completion expected in Q2 2024. Here we present an overview of the current study status, including any information relating to screening failures and the experience of collecting these data as part of a large multicountry, multicentre study.

To date, most large, industry-sponsored studies testing various compounds to address cognitive function have failed to show proof-of-clinical concept. Demonstration of efficacy of iclepertin in improving cognition in this Phase III programme would provide important insight into the role of glutamate in cognitive symptoms, that may also have relevance for other cognitive disorders. Iclepertin may represent the first efficacious medication for CI associated with schizophrenia.

P. Falkai Consultant of: Advistory board Boehringer Ingelheim Pharma GmBH & Co. KG, C. Reuteman-Fowler Employee of: Boehringer Ingelheim Pharma GmBH & Co. KG, Z. Blahova Employee of: Boehringer Ingelheim Pharma GmBH & Co. KG, S. Ikezawa Consultant of: Financial agreements with Boehringer Ingelheim Pharma GmbH, Merck, Biogen and Sunovion, S. Marder Grant / Research support from: Boehringer Ingelheim, GW Pharma, Consultant of: Boehringer Ingelheim, Merck, Sunovion, J. Krystal Shareolder of: Co-founder of Freedom Biosciences, Inc Investments in Biohaven Pharmaceuticals, Sage Pharmaceuticals, Spring Care, Biohaven Pharmaceuticals Medical Sciences, EpiVario, RBNC Therapeutics, Terran Biosciences and Tempero Bio., Consultant of: Aptinyx, Atai Life Sciences, AstraZeneca Pharmaceuticals, Biogen, Biomedisyn Corporation, Bionomics, Boehringer Ingelheim International, Cadent Therapeutics, Clexio Bioscience, COMPASS Pathways, Concert Pharmaceuticals, Epiodyne, EpiVario, Greenwich Biosciences, Heptares Therapeutics, Janssen, Jazz Pharmaceuticals, Otsuka America Pharmaceutical, Perception Neuroscience Holdings, Spring Care, Sunovion Pharmaceuticals, Takeda Industries, Taisho Pharmaceutical Co Advistory board: Biohaven Pharmaceuticals, BioXcel Therapeutics, Cadent Therapeutics, Cerevel Therapeutics, Delix Therapeutics, EpiVario, Eisai, Jazz Pharmaceuticals, Novartis, PsychoGenics, RBNC Therapeutics, Tempero Bio and Terran Biosciences;

Treatment resistant schizophrenia (TRS) affects at least 15-20% of newly diagnosed patients with schizophrenia. Clozapine treatment for this sub-group of patients should be considered immediately after the failure in response to two antipsychotics (usually risperidone and olanzapine) received in adequate doses and time. Immune changes have been reported in first episode patients with psychosis, although results from various studies remain inconclusive. Very few studies have investigated so far cytokine and adipokine changes in TRS.

To measure Interleukin-4 (IL-4), Tumor Growth Factor-β2 (TGF-β2), adiponectin and resistin in a sample of forty first-episode patients with psychosis (FEP) who proved to be treatment resistant (TRS),after treatment with two atypical antipsychotics ( olanzapine and risperidone) and after clozapine treatment.

Serum levels of adiponectin, resistin, IL-4 and TGF-β2 were measured by enzyme linked immunosorbent assay (ELISA) before and after clozapine treatment. Psychopathology was assessed with the Positive and Negative Syndrome Scale (PANSS) before and after clozapine treatment, BMI was calculated in the days of blood sample collection.

We observed a significant decrease of adiponectin levels after switching from olanzapine/risperidone to clozapine (p<0.0001, Wilcoxon signed rank test W=820.0) and a statistically significant increase of resistin levels after switching to clozapine (p<0.0001, Wicoxon signed rank test W=-658.0). Similarly, a significant increase of TGF-β2 and of IL-4 levels was found after clozapine treatment (p=0.039, Wilcoxon signed rank test test W=-454.0 and p=0.029, Wilcoxon signed rank test W=-386.0, respectively).

Resistin, IL-4 and TGF-β levels increase after clozapine treatment while adiponectin levels significantly decrease. The findings may of importance, since they may reflect specific immune changes to clozapine responders.

None Declared