With increasing urbanization, more people are exposed to mental health risk factors stemming from the urban social or physical environment. However, research on urbanization and depression is not clear.

This study aimed to explore environmental and social factors with depression symptoms in view of a network theory of mental health disorders.

The study was conducted among a representative sample of 3,296 habitants of Metropolis GZM (63% of women)– the most urbanized region in Poland. The measurements used were PHQ-9, UCLA, Neighbourhood Cohesion (Neighbourhood Belonging and Social Cohesion), REAT 2.0 (Quality of architecture in neighborhood area), distance and frequency use of green public areas, Self-Rated Health, Physical Activity, size of place of residence per person.

The prevalence of depression risk in villages (N=713), towns under 20,000 (N=219), towns (under 99,000; N=823), and cities (under 300,000; N=1541) was 44.2%, 44.7%, 39.2%, and 34.9% respectively.

The depression nodes with the highest centrality degree and expected influence were PHQ9 (suicidal thoughts), PHQ2 (feeling depressed), and neighborhood belonging. Living in a more urbanized area (UA) had a smaller centrality degree in the network. Edges between PHQ9 and environmental factors were mediated by loneliness (UCLA). Poor architectural conditions (REAT) were linked positively with neighborhood belonging and adversely with social cohesion. Living in UA was negatively related to PHQ9, PHQ5 (eating control), and PHQ2, social cohesion, and green area distance, while positively to PHQ7 (problems with being focused), poor physical health, REAT, and neighborhood belonging (Figure 1).

Living in a city is negatively related to the most central depression symptoms. Even though social cohesion is negatively linked to UA, neighborhood belonging is higher in more urbanized areas.

The balance between detrimental environmental factors and those that protect mental health requires a better understanding of the interaction between urban living and depression.

None Declared

Major depressive disorder (MDD) is a prevalent and disabling condition. Approximately 30-50% of patients do not respond to first-line medication or psychotherapy. Therefore, several studies have investigated the predictive potential of pretreatment severity rating or neuroimaging features to guide clinical approaches that can speed optimal treatment selection.

To evaluate the performance of 1) severity ratings (scores of Hamilton Depression/Anxiety Scale, illness duration, and sleep quality, etc.) and demographic characteristic and 2) brain magnetic resonance imaging (MRI) features in predicting treatment outcomes for MDD. Second, to assess performance variations among varied modalities and interventions in MRI studies.

We searched studies in PubMed, Embase, Web of Science, and Science Direct databases before March 22, 2023. We extracted a confusion matrix for prediction in each study. Separate meta-analyses were performed for clinical and MRI studies. The logarithm of diagnostic odds ratio [log(DOR)], sensitivity, and specificity were conducted using Reitsma’s random effect model. The area under curve (AUC) of summary receiver operating characteristic (SROC) curve was calculated.

Subgroup analyses were conducted in MRI studies based on modalities: resting-state functional MRI (rsfMRI), task-based fMRI (tbfMRI), and structural MRI (sMRI), and interventions: antidepressant (including selective serotonin reuptake inhibitors [SSRI]) and electroconvulsive therapy (ECT). Meta-regression was conducted 1) between clinical and MRI studies and 2) among modality or intervention subgroups in MRI studies.

We included ten studies used clinical features covering 6494 patients, yielded a log(DOR) of 1.42, AUC of 0.71, sensitivity of 0.61, and specificity of 0.74. In terms of MRI, 44 studies with 2623 patients were included, revealing an overall log(DOR) of 2.53. The AUC, sensitivity, and specificity were 0.89, 0.78, and 0.75.

Studies using MRI features had a higher sensitivity (0.89 vs. 0.61) in predicting treatment outcomes than clinical features (P < 0.001). RsfMRI had higher specificity (0.79 vs. 0.69) than tbfMRI subgroup (P = 0.01). No significant differences were found between sMRI and other modalities, nor between antidepressants (SSRIs and others) and ECT. Antidepressant studies primarily identified predictive imaging features in limbic and default mode networks, while ECT mainly focused on limbic network.

Our findings suggest a robust promise for pretreatment brain MRI features in predicting treatment outcomes in MDD, offering higher accuracy than clinical studies. While tasks in tbfMRI studies differed, those studies overall had less predictive utility than rsfMRI data. For MRI studies, overlapping but distinct network level measures predicted outcomes for antidepressants and ECT.

None Declared

Current ketamine-based therapies for treatment-resistant depression (TRD) often induce dissociative effects. A novel oral PR ketamine formulation (KET01) results in a low and delayed peak concentration of ketamine, high hydroxynorketamine concentration, and is associated with limited dissociative properties.

To investigate efficacy, safety, and pharmacokinetics of KET01 in TRD.

KET01-02 was a randomized, double-blind phase 2 trial in outpatients with TRD comparing adjunct 120 mg (n=42) or 240 mg (n=40) oral KET01 once-daily for 3 weeks to placebo (PBO, n=40). The primary endpoint was change from baseline in the MADRS mean score on Day 21. KET01-03 was a randomized, double-blind, cross-over phase I trial in 26 healthy volunteers comparing single doses of 240 mg oral KET01 and 84 mg an approved intranasal formulation of eketamine. The primary endpoint was maximum change of Clinician-Administered Dissociative States Scale (CADSS) score from baseline.

KET01-03 trial; the mean (±SD) maximum change of CADSS score within 24 hours after dosing was 29.6±12.5 for intranasal eketamine and 0.7±1.7 for KET01 (p<0.00000000001). KET01-02 trial; no differences in CADSS score (range: 0.2 to 1.3), and heart rate and blood pressure were observed between the groups on Day 1 and beyond. 10%, 12%, and 15% of patients in the PBO, 120 mg/day, and 240 mg/day KET01 groups, respectively had CADSS score >4 and increase from baseline. At 7 hours post first KET01 dose (240 mg), plasma concentration of ketamine (38.7±27.0 ng/ml) was lower than its metabolites norketamine (267.5±81.6 ng/ml) and hydroxynorketamine (190.2±85.5 ng/ml). 240 mg/day KET01 induced clinically relevant reduction from baseline in MADRS score already within the first 7 hours of treatment (-7.65; Δ vs PBO: -2.22, n.s.), with a statistically significant separation on Day 4 (-10.02; Δ vs PBO: -3.66, p=0.020) and Day 7 (-12.21; Δ vs PBO: -3.95, p=0.042). MADRS score decrease was sustained throughout Day 21 (-13.15; Δ vs PBO: -1.82, n.s.), and during 4-week follow-up (-12.51; Δ vs PBO: -3.35, n.s.). Treatment-emergent adverse events occurred in 47.5%, 50.0%, and 62.5% of patients in the PBO, 120 mg/day, and 240 mg/day KET01 group, respectively.

Oral 240 mg/day KET01 induces a rapid, and clinically relevant reduction of depressive symptoms with only minimal signs of dissociation, potentially due to lower ketamine levels and increased norketamine and hydroxynorketamine levels compared to intravenous administration. Our results suggest that KET01 may be an efficacious and safe take-at-home adjunct treatment for TRD.

C. zu Eulenburg Employee of: HMNC Brain Health, E. Papanastasiou Employee of: HMNC Brain Health, K. Schmid Employee of: Develco Pharma, A. Damyanova Employee of: HMNC Brain Health, A. Glas Employee of: HMNC Brain Health, C. Strote Employee of: HMNC Brain Health, L. Arvastson Employee of: HMNC Brain Health, H. Eriksson Employee of: HMNC Brain Health

Cognitive Behavioral Therapy (CBT) and Acceptance and Commitment Therapy (ACT) seem be similarly effective for the treatment of major depressive disorder (MDD). However, much remains unknown about the differences in underlying psychological mechanisms of change. Assessing dynamic change of depressive symptoms and treatment-specific psychological constructs over time may yield important insights.

The current study will be the first to compare dynamic symptom networks in randomized groups of two psychotherapies by using dynamic time-warp (DTW) analyses.

We reanalyzed data from a randomized controlled trail of 82 patients suffering from MDD. Three depressive symptom subscales (mood, sleep, appetite/weight) and three treatment-related constructs (dysfunctional attitudes, decentering, and experiential avoidance) were collected at 7 time-points before, during, after treatment, and at up to 12 months follow-up. The DTW-analysis modeled the temporal dynamics of depressive symptoms and treatment-related constructs within each individual after which the findings were aggregated on the group-level. Undirected and directed networks were constructed, of which the latter yielded in- and out-strength for each node, that were compared between treatment arms.

Networks based on symptom and construct dynamics markedly differed between treatment arms. Within the CBT-arm a decrease of experiential avoidance was related to a decrease in dysfunctional attitudes (d = 0.059, p = 0.008). Within the ACT-arm a decrease of mood symptoms was related to a decrease of experiential avoidance (d = 0.051, p = 0.04) and an increase of decentering was related to a decrease in sleep symptoms (d = 0.038, p = 0.02) and appetite/weight symptoms (d = 0.049, p = 0.03).

DTW offers a promising alternative approach to study and compare working mechanisms of different treatment interventions. Comparing CBT and ACT revealed a decrease in experiential avoidance within CBT and an increase in the ability to decenter within ACT. However, within both treatments a change in other constructs, suggesting that a first alleviation of mood symptoms is important to activate underlying psychological change.

None Declared

Major depressive disorder (MDD) is a tremendous global disease burden and the leading cause of disability worldwide. Unfortunately, individuals diagnosed with MDD typically experience a delayed response to traditional antidepressants and many do not adequately respond to pharmacotherapy, even after multiple trials. The critical need for novel antidepressant treatments has led to a recent resurgence in the clinical application of psychedelics, and intravenous ketamine, which has been investigated as a rapid-acting treatment for treatment resistant depression (TRD) as well acute suicidal ideation and behavior. However, variations in the type and quality of experimental design as well as a range of treatment outcomes in clinical trials of ketamine make interpretation of this large body of literature challenging.

This umbrella review aims to advance our understanding of the effectiveness of intravenous ketamine as a pharmacotherapy for TRD by providing a systematic, quantitative, large-scale synthesis of the empirical literature.

We performed a comprehensive PubMed search for peer-reviewed meta-analyses of primary studies of intravenous ketamine used in the treatment of TRD. Meta-analysis and primary studies were then screened by two independent coding teams according to pre-established inclusion criteria as well as PRISMA and METRICS guidelines. We then employed metaumbrella, a statistical package developed in R, to perform effect size calculations and conversions as well as statistical tests.

In a large-scale analysis of 1,182 participants across 51 primary studies, repeated-dose administration of intravenous ketamine demonstrated statistically significant effects (p<0.05) compared to placebo-controlled as well as other experimental conditions in patients with TRD, as measured by standardized clinician-administered and self-report depression symptom severity scales.

This study provides large-scale, quantitative support for the effectiveness of intravenous, repeated-dose ketamine as a therapy for TRD and a report of the relative effectiveness of several treatment parameters across a large and rapidly growing literature. Future investigations should use similar analytic tools to examine evidence-stratified conditions and the comparative effectiveness of other routes of administration and treatment schedules as well as the moderating influence of other clinical and demographic variables on the effectiveness of ketamine on TRD and suicidal ideation and behavior.

None Declared

Despite its apparent efficacy in the treatment of a range of psychiatric disorders, electroconvulsive therapy (ECT) is viewed by some as a contentious treatment. Although most clinicians and researchers consider ECT a safe and effective treatment, there are ongoing and significantly publicised concerns about potential side effects.

To explore use of ECT across Scotland in a large naturalistic clinical sample across an 11-year period from 2009 to 2019. To consider the efficacy and side effects of ECT for a range of common psychiatric disorders including, depression, bipolar depression, schizophrenia, and mania.

Using data from the Scottish Electroconvulsive Therapy (ECT) Accreditation Network (SEAN), information was collected for all adults who had received ECT. Variables included age, sex, Scottish Index of Multiple Deprivation (SIMD) quintile, International Classification of Diseases, Tenth Edition (ICD-10) diagnosis, indication for ECT, Mental Health Act status, consent status, entry and exit Montgomery-Asberg Depression Rating Scores (MADRS), entry and exit Clinical Global Index Severity CGI-S) scores and reported side effects. Side effects were recorded as present if the side effect was reported at any point during the episode of treatment.

4826 ECT episodes were recorded. The majority of episodes were in women (68.4%, n=3,301). Average age at treatment onset was 58.52 years. Males were slightly younger (m=58.24 years vs f= 58.65 years, p= 0.20). Mean number of treatments/episode was 9.59 (95% CI 9.32 – 9.85). Mean treatment dose delivered was 277.75mC (95%CI 272.88 – 282.63mC).

2920 episodes of treatment had CGI-S entry and exit recorded. At entry, mean CGI-S indicated marked illness (5.03 95% CI 4.99-5.07). Recipients with schizophrenia had the highest CGI-S score (5.45 95% CI 5.21-5.60), followed by those with post-partum disorders (5.38, 95% CI 4.61-6.14). At exit, mean CGI scores indicated borderline illness (2.07, 95% CI 2.03-2.11), recipients diagnosed with mixed affective state had the lowest CGI-S score (1.72, 95% CI 0.99-2.47) followed by those with schizoaffective disorder (2.01, 95% CI 1.76-2.42).

Anaesthetic complications (n=34) and prolonged seizures (n=38) were rare, occurring in <1% of treatment episodes. Cardiovascular complications were reported in 2.2% (n= 102). Nausea was reported in 7.2% (n= 334) and muscle aches in 12% (n=560). Confusion was reported in 19% (n=879) and cognitive side effects were reported in 26.2% (n=1212). One third of treatment episodes reported confusion or cognitive side effects (33.1%, n=1545).

From this large naturalistic clinical sample, ECT appears to be effective in improving illness severity as measured by CGI-S score. While some side effects (such as prolonged seizures and cardiovascular complications) were rare, others (such as confusion or cognitive side effects) were relatively common.

None Declared

In a 12-week, Phase II (NCT02832037) trial, iclepertin (BI 425809), an inhibitor of glycine transporter-1, was generally well tolerated and significantly improved cognition in 509 patients with schizophrenia.

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

The CONNEX programme includes 3 randomised, double-blind, placebo-controlled parallel group trials in patients with schizophrenia (NCT04846868, NCT04846881, NCT04860830) receiving stable antipsychotic treatment. Each trial aims to recruit ˜586 patients, 18–50 years old, treated with 1–2 antipsychotic medications (≥12 weeks on current drug and ≥35 days on current dose before treatment) who have functional impairment in day-to-day activities and interact ≥1 hour per week with a designated study partner. Patients with cognitive impairment due to developmental, neurological or other disorders, with a current DSM-5 diagnosis other than schizophrenia or receiving cognitive remediation therapy within 12 weeks prior to screening, will be excluded. Patients will be recruited from multiple centres across 41 countries in Asia, North and South America, Europe and the Asia-Pacific Region, and randomised 1:1 to receive either iclepertin 10 mg (oral administration; n=293), or placebo (n=293) once daily for 26 weeks. The primary endpoint is change from baseline in overall composite T-score of the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery. The key secondary endpoints are change from baseline in total score on the Schizophrenia Cognition Rating Scale and change from baseline in the adjusted total time T-score in the Virtual Reality Functional Capacity Assessment Tool.

The CONNEX programme is currently recruiting (Table); the first patients were enrolled in Aug–Sept 2021 and completion is expected in Q1 2025. The presentation will describe the current study status, information relating to screening failures, and the experience of collecting these data as part of a large multi-country, multicentre study.Table.

The number of patients recruited by 31 August 2023

Iclepertin may represent the first efficacious medication for cognitive impairment associated with schizophrenia.

Boehringer Ingelheim

C. Reuteman-Fowler Employee of: Boehringer Ingelheim, Z. Blahova Employee of: Boehringer Ingelheim, S. Ikezawa Consultant of: Boehringer Ingelheim Pharma GmbH, Lundbeck, Takeda Pharma, Sumitomo Dainippon Pharma, Employee of: International University of Health and Welfare, Mita Hospital, Tokyo, Japan, S. Marder Consultant of: Boehringer Ingelheim Pharma GmbH, Merck, Biogen and Sunovion, P. Falkai Consultant of: Boehringer Ingelheim Pharma GmbH, Boehringer Ingelheim Pharma Advisory Board, J. H. Krystal Shareolder of: Freedom Biosciences, Inc., 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.; Biohaven Pharmaceuticals, BioXcel Therapeutics, Cadent Therapeutics, Cerevel Therapeutics, Delix Therapeutics, EpiVario, Eisai, Jazz Pharmaceuticals, Novartis, PsychoGenics, RBNC Therapeutics, Tempero Bio and Terran Biosciences Advisory Boards

Evidence from observational and genetic studies suggests a bidirectional relationship between loneliness and psychosis. To our knowledge, no previous study has assessed the association between loneliness in childhood and first-episode psychosis (FEP).

We aimed to assess the association between loneliness in childhood and the odds of FEP and clinical variables of interest (i.e., diagnosis and clinical and functional severity) in FEP and to explore gender differences in this association.

This was an observational, case-control study, based on the AGES-CM cohort, a longitudinal prospective study including patients with FEP ages 7-40, their first-degree relatives, and an age- and sex-matched sample of controls in seven university hospitals in the region of Madrid. We assessed loneliness in childhood with the question “Have you ever felt lonely for more than 6 months before the age of 12” and objetive social isolation with the peer relationships item from the childhood subscale of the Premorbid Adjustment Scale. We conducted logistic and linear regression analyses to assess the association between childhood loneliness and i) the odds of presenting a FEP and ii) clinical variables of interest (diagnosis and scores on positive, negative, general, depressive, and manic symptoms and functioning), while adjusting for demographic variables.

The study sample comprised 285 patients with FEP (32.6% female, age 24.50 ± 6.2 years) and 546 controls (48.7% female, age 25.93 ± 5.5 years). Loneliness in childhood was associated with increased odds of FEP (adjusted odds ratio; aOR: 2.17, 95% CI [1.40-3.51], p=.002). This association remained significant after controlling for objective social isolation in childhood (aOR:2.70, IC 95% [1.58-4.62], p<.001).

The effect of the association was stronger in females (aOR:4.74, 95% CI [2.23-10.05], p<.001) than in males (aOR:1.17, IC 95% [0.63-2.19], p=.623). In females with FEP, loneliness in childhood was significantly associated with increased odds of receiving a diagnosis of other psychosis (aOR:0.155, 95% CI [0.048-0.506], p=.002) relative to an SSD diagnosis. In the FEP sample, loneliness in childhood was associated with greater severity of positive and affective symptoms and worse functioning.

Loneliness in childhood is associated with increased odds of FEP and clinical variables of interest. This suggests the potential role of this phenotype as an early risk marker for psychosis that could help guide targeted interventions.

C. Díaz-Caneja Grant / Research support from: Instituto de Salud Carlos III (PI17/00481, PI20/00721, JR19/00024), European Union, Consultant of: Angelini, L. Donaire: None Declared, V. Cavone: None Declared, Á. Andreu-Bernabeu: None Declared, J. González-Peñas: None Declared, M. Díaz-Marsá: None Declared, R. Rodríguez-Jiménez: None Declared, Á. Ibáñez: None Declared, E. Baca-García: None Declared, J. C. Leza: None Declared, M. F. Bravo-Ortiz: None Declared, J. L. Ayuso-Mateos: None Declared, C. Arango Grant / Research support from: Madrid Regional Government (R&D activities in Biomedicine S2022/BMD-7216 AGES 3-CM), Instituto de Salud Carlos III, European Union, Consultant of: Acadia, Angelini, Biogen, Boehringer, Gedeon Richter, Janssen Cilag, Lundbeck, Medscape, Menarini, Minerva, Otsuka, Pfizer, Roche, Sage, Servier, Shire, Schering Plough, Sumitomo Dainippon Pharma, Sunovion and Takeda

Verbal fluency, a cognitive function that reflects executive functions and the rapid retrieval of pertinent information from memory, has yielded inconsistent findings in previous research on autism spectrum disorder (ASD), however in schizophrenia (SCH) semantic fluency exhibits a more pronounced impairment compared to letter fluency.

In this study we aim to comprehensively investigate verbal fluency in ASD, SCH, and neurotypical healthy control individuals (NTP). The primary objective is to investigate disparities in novel response generation, specifically between the ASD, SCH and NTP groups, using phonemic and semantic fluency tasks. Three central inquiries guide our research: (1) whether differences between groups (ASD, SCH, and NTP) can be identified in word productivity, clustering, errors, and perseverations; (2) whether participants with ASD and SCH exhibit different word production with elevated imageability and concreteness values; and (3) if individuals with ASD and schizophrenia demonstrate reduced productivity during the earlier phases of fluency tasks.

Forty participants with ASD (12 female, 24 male, 4 other, mean age: 30.5), 39 with SCH (10 female, 28 male, 1 other, mean age: 34.7) and 41 NTP (13 female, 28 male, mean age: 31.0) were recruited from the outpatient units of the Department of Psychiatry and Psychotherapy, Semmelweis University. Participants were requested to list as many words as they could on two phonemic and two semantic category conditions. Audio recordings were later transcribed. To assess concreteness and imageability, we employed a seven-point scale and recruited independent external raters to evaluate a total of 1481 words.

Preliminary results indicate that the three study groups did not differ significantly in phonemic fluency (F(2, 119)= 0.983, p=0.377), during either time period. However, a significant difference was observed in semantic fluency (F(2, 119)= 6.531, p=0.002). Post-hoc tests (Tukey corrected) revealed that this difference stemmed from impaired performance in the SCH group. Participants with schizophrenia (SCH) exhibited reduced semantic word productivity compared to both neurotypical (NTP) individuals and participants with ASD (Figure 1). However, there were no significant differences between participants with ASD and NTP individuals.

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In conclusion, our study investigated the characteristics of verbal fluency in a transdiagnostic approach. While phonemic fluency did not reveal significant differences among the three groups, our analysis of semantic fluency unveiled a distinction. Specifically, individuals with schizophrenia exhibited impaired semantic word productivity. Our study highlights the complex nature of verbal fluency impairments in different conditions and the importance of considering more nuanced methods when assessing cognitive functions.

None Declared

Schizophrenia is a major mental disorder with a high risk of suicide, which is one of the leading causes of early death in schizophrenia patients. It is known that suicidal behavior is 20-50 times higher in schizophrenia patients compared to the general population. Clinical features makes it difficult to determine the risk of suicide in this patient group. Since genetic studies on suicides of patients with schizophrenia are limited, this area was deemed worthy of research.

CircRNAs can potentially serve as minimally invasive biomarkers because they can freely cross the blood-brain barrier. It is aimed to define the effect of circRNA molecules on suicidal behavior in patients diagnosed with schizophrenia and other schizophrenia spectrum psychotic disorders, and to increase protective and preventive approaches by predicting possible consequences of suicidal behavior.

104 patients followed up with the diagnosis of schizophrenia and and other schizophrenia spectrum psychotic disorders were included in the study. RNA was isolated from the blood taken into a hemogram tube, and three cirRNA molecules were identified using a number of RNA sequencing techniques. In addition, sociodemographic characteristics of the participants, clinical features of the disease, suicidal behavior history, current treatment status were questioned in detail. Simultaneously, the current clinical status was evaluated with clinical evaluation scales as Positive and Negative Syndrome Scale (PANSS), Calgary depression scale for schizophrenia (CDSS), Suicide Probability Scale (SPS), Beck Suicidal Intend Scale (BSIS).

Three circRNA molecules were identified, chr3_196488683, chr5_69175537 and hsa_circ_0084021. No significant difference was found between these molecules and past suicide attempts. It was found that chr5_69175537 was negatively associated with the age of onset of psychotic disorder negative symptoms, and hsa_circ_0084021 was negatively associated with the age of onset of both negative and positive symptoms. When the relationship between the clinical assessment scales and suicidal behavior was evaluated, the PANSS general symptoms subscale score was significantly higher in the group with suicidal behavior (p<0.05). CDSS mean scores and BSIS scores were also found to be significantly higher in the group with previous suicide attempts (p<0.01).

Although our findings do not allow definitive conclusions due to the complex interaction between epidemiological and clinical factors and limited literature, it has shown that schizophrenia contains many risks that increase suicidal behavior. To predict suicide, circRNA molecules need to be supported by prospective studies with large sample groups and comparison with control groups.

None Declared

D-serine and the DAO enzyme may impact the NMDA receptor and contribute to schizophrenia, but the exact role and outcomes are not fully understood due to the complexity of the disorder.

We analyzed serum levels of d-serine and DAO in untreated individuals with schizophrenia during acute psychotic episodes. We correlated these factors with clinical characteristics and compared results to a healthy control group. We also examined any differences after six months of treatment.

The study involved 89 patients with schizophrenia or related psychotic disorders who were hospitalized due to psychotic episodes. Also, the study had 81 healthy participants matched in terms of gender, age, and smoking status with the patient group. PANSS, CGI, GAS, CDSS, and MoCA were applied to determine the severity of the disease. Serum d-serine and DAO levels were measured by ELISA kits.

During an acute psychotic episode, patients had significantly lower levels of D-serine, DAO, and D-serine/DAO ratio compared to healthy individuals (Z=6.52, p<0.001; Z=4.54, p<0.001; Z=2.90, p=0.004). Although DAO and D-serine levels increased with symptom regression after six months of treatment, the D-serine and D-serine/DAO ratios were significantly lower in patients than in healthy individuals(Z=3.52, p<0.001; Z=3.44, p<0,001). There was no correlation between the change in D-serine level and the change in scale scores. However, there was a negative correlation between the change in DAO level and the change in PANSS total (r=-0.681, p=0.000), anxiety scores (r=-0.336, p=0.032), and Calgary depression score (r=-0.547, p=0.000). There was a positive correlation between the change in D-serine/DAO ratio and the change in the Calgary depression scale score (r=0.353, p=0.024) in addition to PANSS positive (r=0.395, p=0.011) and total scores (r=0.585, p=0.000). Antipsychotic doses negatively correlated with the changes in DAO level (r=0.421, p=0.01). It was found that the female patients had significantly lower levels of DAO than the female healthy subjects (Z=-5.061, p<0.001). No correlation was found between serum D-serine level, DAO level, and the D-serine/DAO ratio with cognitive function. D-serine level negatively correlated with age(r=-0.265, p=0.012) and age at onset of the disease (r=-0.227, p=0.032).

The findings support the view that D-serine and DAO may play a role in the pathophysiology of schizophrenia and related psychotic disorders. To better understand the relationship between D-serine metabolism and symptom clusters in psychosis and the effects of antipsychotic drugs on NMDAR dysfunction, further studies that directly measure DAO enzyme activity and examine cognitive symptoms in more detail are needed.

None Declared

Mental health legislation allows for involuntary care of patients with severe mental disorders, assuming it improves health and reduces risk. Professionals have warned against potentially adverse effects of recent initiatives to heighten involuntary care threshold, such as CRPD and national coercion-reduction strategies. We have not found that the impact of high thresholds for involuntary care have been studied.

Our aim was to use national data from Norway to test implications of the hypothesis that areas with lower levels of involuntary care show higher levels of morbidity and mortality in their severe mental disorder populations compared to areas with higher levels. We pre-specified five models of how such adverse effects could manifest in national register data.

Using national register data, we calculated standardized (by age, sex, and urbanicity) involuntary care ratios across Community Mental Health Center areas in Norway. For patients diagnosed with severe mental disorders (ICD10 F20-31), we tested whether lower area ratios in 2015 interacted with 1) case fatality over four years, 2) an increase in inpatient days, and 3) time to first episode of involuntary care over the following two years. We also assessed 4) whether area ratios in 2015 predicted an increase in the number of patients diagnosed with F20-31 in the subsequent two years and whether 5) standardized involuntary care area ratios in 2014–2017 predicted an increase in the standardized suicide ratios in 2014–2018.

We included 21481 patients with either an F20-31 diagnosis, an episode of involuntary care in 2015, or both. The standardization variables age, sex, and urbanicity explained 70.5% of the variance in raw rates of involuntary care, and the remaining extremal quotient was 2.5. Age and sex predicted case-fatality, but involuntary care-rate was insignificant. Patients with F20-31 and no involuntary care episode in 2015 showed a steady reduction in inpatient days the following years, but not significantly related to the area’s involuntary care rates. For the same sample, these rates did not predict the time to an episode of involuntary care. The area’s involuntary care rate in 2015 did not predict changes in the number of patients in treatment for a diagnosis of F20-31 from 2015-2017. Finally, the area’s involuntary care rate from 2014-2018 explained 1.2% of the variance in suicides in 2014-2019 in the area.

In the models, we found no significant associations between low standardized catchment area rates of involuntary care and the pre-specified outcomes. This raises questions about some assumptions in mental health legislation and merits further research.

None Declared

Cognitive impairment associated with schizophrenia (CIAS) is an important unmet need as there are no effective treatments available. Iclepertin (BI 425809), a glycine transporter-1 inhibitor, has been shown to improve CIAS in Phase II trials, and Phase III trials are underway.

The ongoing CONNEX-X extension study aims to collect additional safety data relating to iclepertin treatment in patients with CIAS.

CONNEX-X (NCT05211947/1346-0014) is a multinational, multicentre, open-label, single-arm extension study in patients with CIAS who completed 26 weeks of treatment (iclepertin 10 mg or placebo) in one of 3 Phase III CONNEX parent trials (NCT04846868/1346-0011, NCT04846881/1346-0012, NCT04860830/1346-0013). An estimated 1400 clinically stable outpatients will be treated (iclepertin 10 mg daily) for 1 year, irrespective of previous treatment (iclepertin/placebo). Patients are excluded if any of the following circumstances occur during the parent study and up to Visit 1 of CONNEX-X: suicidal behaviour or ideation (type 5 on the Columbia-Suicide Severity Rating Scale), diagnosis with moderate/severe substance use disorder, diagnosis other than schizophrenia (according to Diagnostic and Statistical Manual of Mental Disorders – Fifth Edition), development of any condition preventing participation, a haemoglobin level decrease (>25% or <100g/L from baseline in parent trial) or haemoglobinopathies. The primary endpoint is the occurrence of treatment-emergent adverse events. The secondary endpoints include change from baseline (CfB) in Clinical Global Impressions-Severity (CGI-S) and CfB in haemoglobin. Further efficacy endpoints include CfB in MATRICS Consensus Cognitive Battery (MCCB) overall composite T-score, CfB in Schizophrenia Cognition Rating Scale total score and CfB in Virtual Reality Functional Capacity Assessment Tool (VRFCAT) total times.

Currently, 460 patients have been enrolled and randomised from the parent trials with 0% screening failures (-80% roll-over rate, 30 August 2023). Current study status, including recruitment, screening failures and data collection experiences, are presented.

Patient enrolment rates from the CONNEX trials to the CONNEX-X open-label extension study are stable. CONNEX-X will allow the exploration of long-term safety, as well as descriptive analyses of cognitive and functional endpoints of iclepertin in the treatment of CIAS.

Boehringer Ingelheim

C. Reuteman-Fowler Employee of: Boehringer Ingelheim Pharmaceuticals, Inc., Z. Blahova Employee of: Boehringer Ingelheim RCV GmbH & Co. KG, S. Marder Consultant of: Boehringer Ingelheim Pharma GmbH, Merck, Biogen and Sunovion, S. Ikezawa Consultant of: Boehringer Ingelheim Pharma GmbH, Lundbeck, Takeda Pharma, Sumitomo Dainippon Pharma, Employee of: International University of Health and Welfare, Mita Hospital, Tokyo, Japan, P. Falkai Consultant of: Boehringer Ingelheim Pharma GmbH, Boehringer Ingelheim Pharma advisory board

Systematic monitoring and evaluation of innovative healthcare programs are essential to develop sustainable solutions to health needs in the population (Porter & Teisberg, 2006). Development of Psychiatric High and Intensive Care Units (HIC’s) in Belgium, following the Dutch Model (van Mierlo et al., 2013), is an innovative model for patients with acute and severe psychiatric illness, resulting in potential danger. HIC aims to provide intensive, need-adapted care with interventions that reduce (perceived) coercion, focusing on participative processes and continuity of care.

(1) What are the clinical characteristics of admitted patients? (2) How does clinical symptomatology evolve during admission? (3) How do patients, relatives and caregivers experience the process of care and recovery? (4) What is the role of HIC’s in the reformed mental health care?

This is an explorative, hypothesis-generating study, using a mixed-method approach, consisting of qualitative and quantitative methods against a value-based framework. Data collection lasted 18 months in the first 9 HIC’s in Belgium. Results are based on validated questionnaires completed by adult patients and their HIC caregivers at admission and discharge (N=472).

We provide the first, preliminary results. Suicidality, psychotic and substance-related symptoms are the most important primary symptoms. Almost 70% have 2 or more symptoms, with psychiatric comorbidity of 50%. Substance-related- and psychotic disorders are the two most common diagnoses, followed by personality disorder cluster B and depressive disorder. 83% have been in residential care in the past, of whom 87% twice or more. The median age is 36 years, but the median age of onset of mental disorders is 21 years, which equals to 15 years in mental disorder progress and comorbidity development. Over 50% meet the criteria for Severe Mental Illness and 56% are involuntary admitted. There is a high degree of unmet needs: no outpatient care is provided for one out of five prior to admission and there is a low follow-up by mobile teams prior to and after admission (around 12% each). We found significant improvements after an average stay of 22 days for aggression, suicidality and crisis (respectively decrease of 68%, 25% and 9%); readiness to change and motivation for treatment (respectively increase of 5% and 14%) The Client Satisfaction Questionnaire scores range from 1 to 4, with an average score 3.15 out of 4.

Based on these preliminary results we can conclude that aggression, suicidality, crisis, readiness to change and motivation for treatment all improve significantly after a short stay of 3 weeks. Despite a vulnerable, severely distressed population, patients are generally satisfied with received care. There is a high degree of unmet needs: insufficient provided outpatient care and low follow up by mobile teams.

None Declared

Involuntary treatments in forensic psychiatry represents a complex intersection of mental health, legal systems and ethics. Judicial authorities may compulsorily refer children to inpatient clinics for receiving necessarily treatment. Despite its importance, there is limited research on the reasons behind and effectiveness of such interventions in minors.

The objectives of this study were to describe the clinical characteristics of minors who have risks of harming themselves and/or others so receiving involuntary treatment due to a court order. It is aimed to assess the effectiveness of involuntary treatment.

A follow-up case series was conducted on 9 minors who hospitalized by court orders in a secure inpatient child and adolescent psychiatry clinic, in the year of 2023. Data collected from medical records, including demographic information, clinical presentation, diagnosis and discharge treatment. After one, three and six month of the discharge, interviews made with the patients and their families. Current data collected on treatment regimen, compliance, behavioral outcomes and reoffending rates. All data were anonymized to maintain patient confidentiality.

The case series consisted of 3 males and 6 females, with a mean age of 16.5 years at the time of admission. The most common reason to hospitalization was homicide risk 88%, followed by substance use 66%. Conduct Disorder was the most common diagnosis with the rate of 88%, followed by Substance Use Disorder(66%) and Attention Deficit and Hiperactivity Disorder(50%). 44% of minors had a history of juvenile delinquency. School dropout rates were 100%. Treatment consisted of a combination of individual and group therapy and medication. Treatment refusal rates were 88% so in terms of treatment, 88% of the minors in this sample treated with depot form antipsychotic medications, with the most common medication being risperidone. Overall all of the sample showed a significant reduction in disruptive behaviors during their hospital stay. Follow-up data collecting is still continue and preliminary statistics show us that relapse rates are low and treatment compliance is relatively high of the sample.

The findings suggest that involuntary hospitalization can be effective in reducing disruptive behaviors and increasing treatment compliance in minors with conduct disorders, substance abuse disorders and a history of juvenile delinquency. These results underscore the need for comprehensive, multidisciplinary approaches that integrate psychiatric treatment, psychoeducation and social support. Given the relatively small sample size and short-term follow-up, further research is needed to determine the long-term effects of involuntary treatment and to identify factors that predict treatment response.

None Declared

In the UK there are 3500 individuals detained in medium secure forensic psychiatry units. Service users in such settings have complex and serious mental illness (SMI), often with co-morbid physical health problems and a life expectancy of at least 10 years shorter than the general population. They often have low levels of physical activity. There is little evidence about physical activity interventions for medium secure service users in the United Kingdom.

Our objective is to co-produce, with medium secure service users, the content and delivery of an intervention to increase physical activity. We shall assess feasibility, acceptability, and pilot data collection methods for outcomes relevant for a future randomised controlled trial.

This is a 30-month mixed-methods project that will follow the Medical Research Council (MRC) framework Developing and Evaluating Complex Interventions. The study has 4 phases. Phases 1-2 will gather information required to co-develop an evidence-based intervention in Phase 3. Phase 4 will assess the intervention in a feasibility study, evaluating and testing the intervention for a future pilot study.

Study settings: Two NHS Medium Secure In-Patient Psychiatric Hospitals in the UK.

This paper presents the preliminary findings from Phase 4 and also offers a highlight into the results from the Women’s Services from both study sites. A total of thirty-three service users from both study sites participated in Phase 4 of the study and twenty-six completed the physical activity intervention, known as the IMPACT Intervention. Between both study sites, there were two Women’s Standard Medium Secure Services and one Women’s Enhanced Medium Secure Service, involved in this study. A total of nine female service users participated in Phase 4.

The preliminary findings of Phases 4 are allowing the team to move forward and evaluate the effect of the IMPACT Intervention.

None Declared

Czech health care workers recently experienced serious challenges to their mental health. After the COVID-19 pandemic that was extremely stressful, a war in Ukraine caused a flood of refugees that needed health care. Although the Czech Republic does not have borders with Ukraine, it welcomed more than 400,000 refugees in 2022.

The aim of this study was to investigate the association between depression and working with Ukrainian refugees among health care workers and the nature of emotional burden connected with this situation.

We use data from an online survey of the Czech COVID-19 HEalth caRe wOrkErS (HEROES) Study collected in September - November 2022 (n=1,076). We combined quantitative binary logistic regression and qualitative content analysis of answers to an open-ended question (“How does the current situation of war in Ukraine affect your mental well-being and working conditions?”). Logistic regression estimated odds ratio (OR) of at least moderate depression, defined as => 10 points on the Patient Health Questionnaire.

Among our participants (75.1% women, mean age 46 (SD 11.0)), 62.1% had experience of working with Ukrainian refugees, and 13.8% reported moderate to severe depression. Logistic regression model (adjusted for potential confounders) indicated that health care workers who worked with Ukrainian refugees had slightly greater chance of having depression, but the association was not statistically reliable (OR 1.05; 95% CI 0.59-1.86). Out of all survey respondents, 867 replied to an open-ended question. As follows from qualitative analysis, three categories of psychological strain were described by the health care workers: 1) specificity of work with the refugee patients (e.g. language barrier, increased workload, opinion conflicts), 2) insecurity, threat of war and fears about future (regarding global and nuclear war, security, future of kids, economic burden, etc.), 3) grief and compassion for the suffering of refugees. It was also frequently mentioned in the responses that war is a greater threat to health care workers than the COVID-19 pandemic.

There is a slight association between working with refugees and depression. However, health care workers are also endangered by general fears of war and insecurity in a nearby country. In this changing world, it is of the greatest importance to pay attention to resilience building and stress prevention programs. Further, health care workers should be offered psychological support and practical resources to deal with the varying workload.

None Declared

Differences in psychiatry training vary substantially across Europe. Such organisations as the European Federation of Psychiatry Trainees (EFPT), the European College of Neuropsychopharmacology, and the European Psychiatry Association, have committed to offer international experiences based on the premise that it could foster international collaboration, aid early career professionals to progress professionally and spark discussion regarding different practices across Europe. To date, there are no studies that focus exclusively on the exchange experience in mental health professionals

I present the synthesis of the ten years answers from 2012 to 2022 to the post-exchange online evaluation form, which trainees had to fill in in order to receive an attendance certificate.

The present study analysed the answers of 202 psychiatry trainees or recent graduates who took part in the EFPT exchange program during 2012 and 2022 and filled in the internet-based evaluation form. The inclusion criteria were currently in training or recently finished training as a psychiatrist in Europe and filling in the questionnaire. The exclusion criterion was participation in the EFPT exchange program for the second or subsequent time.

All trainees were systemically asked to complete the online evaluation form after the exchange period. The form includes sociodemographic, training in host country-related, and exchange experience-related questions. Experience measures were evaluated using the 4-point Likert scale. Data was anonymized before the analysis. The study followed the principles of the Declaration of Helsinki.

The majority of participants were females in the second half of their training. The average age was 29 years. The largest number of applicants were from Turkey, whereas the United Kingdom hosted the most participants. One-third of the participants had previous international exchange experience. Most trainees were exposed to both outpatient and inpatient treatment settings and were involved in educational or research activities. 96.7% of participants indicated that they were satisfied or very satisfied with the experience, 95.6% said that the exchange was useful or very useful, and 98.9% were likely or very likely to recommend exchange to colleagues.

To my knowledge, this study is the first to assess the experience of psychiatry trainees who went on exchange during their professional training. Vast majority of trainees were satisfied with their exchange, thought it would be useful for their clinical practice and would recommend it to their colleagues. These findings are in line with other studies that examined medical exchange experiences .

None Declared

Beaumont Hospital is the National Neurosurgical Centre in Ireland. Due to the high numbers of referrals from Neurology and Neurosurgery, The Department of Psychiatry established a specialist Neuropsychiatry inpatient Liaison service and a weekly Neuropsychiatry outpatient clinic. Many of the referrals that the service receive involve the management of delirium. Delirium is a common medical complication, particularly in neurosurgical settings. Delirium causes significant symptom burden which can lead to distress to all involved and impacts quality of life.

The aim was to improve the rates of referrals for delirium presentations and referral rates overall from Neurology and Neurosurgery. The neuropsychiatry service have implemented a delirium protocol for all medical and surgical teams in Beaumont Hospital. This protocol can be accessed through the Beaumont hospital phone app, or on site on each ward. For this reason, delirium can be managed by medical teams in the first instance. If this is not successful, neuropsychiatry can be contacted for further advice or review of patients with more complicated presentations.

The neuropsychiatry service receives referrals through the Patient Information Profile Explorer system which is accessed through the Beaumont Hospital online portal. In the event of an urgent referral, neurology or neurosurgery teams can contact the neuropsychiatry service directly by phone. Referrals are logged on the team referral log book, and details of the referral are recorded along with diagnosis and management. Data was collected retrospectively from the PIPE and log book to measure the rates and reasons for referrals over a one year period. Rates and details of referrals were initially recorded between July-December 2022. An educational intervention was provided where psychoeducation was provided to junior hospital doctors during protected teaching times and further education was provided over the phone when referrals were discussed between team members. Rates and details of referrals were then recorded between January-July 2023.

There was a reduction in referrals when comparing the two six month periods. There were 115 neuropsychiatry referrals from July to December 2022 and 78 referrals from January to July 2023. Rates of delirium referrals also reduced from 31% to 25% after psychoeducation was provided to junior doctors.

This audit highlights the importance of communication and education for medical and surgical trainees in the management of delirium. There is a high rate of turnover of junior doctors throughout the year in Beaumont Hospital. For this reason, it is imperative that continued education is provided to allow them to follow the delirium protocol independently before seeking tertiary service assistance. Ultimately, early and rapid intervention of delirium can have a positive impact on patient care and prognosis

None Declared

Hyponatremia (hypoNa) is a potentially serious adverse event of treatment with antidepressants. Previous research suggests that risk of drug-induced hyponatremia differs between antidepressants.

This meta-analysis sought to determine the risk of antidepressant-induced hypoNa, stratified by different compounds and classes.

PubMed and Web of Science were searched for studies reporting on incidence or risk of hypoNa in adults using antidepressants (PROSPERO, CRD42021269801). We modelled random-effects meta-analyses to compute overall incidence and risk of any and clinically relevant hypoNa for each compound and class, and ran head-to-head comparisons based on hypoNa incidences. We conducted subgroup analyses for geriatric populations, study context and sodium cut-off value.

Thirty-nine studies (n = 8,459,033) revealed that exposure to antidepressants was associated with significantly increased odds of hypoNa (OR = 2.82 (1.79 – 4.45)). The highest event rates were found for SNRIs (7.17%), SSRIs (5.20%), and TCAs (2.26%); the lowest for mirtazapine (1.02%) and trazodone (0.89%). The highest odds ratios were found for MAOIs (4.12 (1.92 – 8.86)), SNRIs (3.16 (1.77 – 5.67)), and SSRIs (2.78 (1.57 – 4.91)); the lowest for mirtazapine (2.82 (1.87 – 4.21)) and TCAs (1.85 (1.28 – 2.69)). Compared to SSRIs, SNRIs were significantly more likely (OR = 1.27 (1.13 – 1.42), p < 0.001) and mirtazapine significantly less likely (OR = 0.61 (0.39 – 0.96), p = 0.032) associated with hypoNa.

Our meta-analysis demonstrated that, while no antidepressant can be considered completely risk-free, for hypoNa-prone patients mirtazapine should be considered the treatment of choice and SNRIs should be prescribed more cautiously than SSRIs and TCAs.

None Declared