Early-life adversity, including pre/perinatal stress and childhood maltreatment (CM), is strongly linked to neurodevelopmental and psychiatric outcomes. However, the specific impact of these stressors and the differential effects in males and females remain poorly understood.

This study aims to investigate the relative and combined impact of maternal psychosocial stress during pregnancy, obstetric complications (OC), and CM on neurodevelopmental delays, emotional/behavioral symptoms, and DSM-5 diagnoses before puberty (12 y.o.), with a focus on sex differences.

211 participants aged 7–17 from the Spanish multicenter Epi_Young_Stress study were included (130 with psychiatric diagnoses and 81 controls). 26.06% of children presented a psychiatric diagnosis and 25.1% a neurodevelopmental disorder before puberty. Hierarchical and logistic regression models were used. Neurodevelopmental subdomains, CBCL dimensions, overall adjustment (CGAS), and DSM-5 diagnoses were the studied outcomes. Predictor variables included socioeconomic status, maternal distress during pregnancy, OC, CM, and IQ. Interaction effects between prenatal and postnatal stressors were tested.

OC were associated with motor and language neurodevelopmental delays and attentional problems and worst adjustment only in males. CM emerged as the most consistent and robust predictor of emotional/behavioral problems, worst overall adjustment and psychiatric diagnoses in both sexes. Interaction effects between OC and CM were found for language, reading and writing problems in males. Vocabulary IQ emerged as a consistent protective factor.

CM is a critical determinant of early psychopathology regardless child’s sex. OC contribute to neurodevelopmental and attentional problems only in males. Findings underscore the need for early identification and sex-specific interventions.

None Declared

Childhood maltreatment (CM) and mental disorders are often chronic conditions associated with poor health outcomes and increased mortality. Recent research indicates that those stressful conditions may accelerate biological ageing by means of epigenetic age acceleration. Little is known about how the exposure to CM and psychopathological symptoms contribute to biological ageing in children and adolescents recently exposed to such conditions.

i) to examine whether CM and psychopathological internalizing/externalizing symptoms impact the pace of ageing, and ii) to study the putative sex differences.

203 children and adolescents (7 to 17 y.o.) from the Epi_Young_Stress project were included. DNA methylation in PBMCs was quantified using the Illumina EPIC_array_v1. Epigenetic pace of ageing was estimated using DunedinPACE clock. CM was evaluated by TASSCV and internalizing/externalizing symptoms with CBCL. Linear regression models were used to test associations between epigenetic ageing, CM and internalizing/externalizing symptoms. Age, socioeconomic status (SES), ancestry and smoking were included as potential confounders.

Lower SES was strongly associated with an accelerated pace of ageing. Stratified analyses revealed sex-specific effects: among females, SES was the primary predictor of increased ageing, while neither CM nor internalizing/externalizing symptoms exerted significant effects. Among males, externalizing symptoms and smoking were significantly associated with an increased pace of ageing.

SES emerged as the strongest determinant of epigenetic ageing in children and adolescents. In males, externalizing behaviors and smoking further contributed to accelerated ageing, underscoring the relevance of lifestyle and psychosocial wellbeing in shaping ageing trajectories early in life.

None Declared

Young British Bangladeshis experience a higher prevalence of mental health problems than their White British peers, yet are underrepresented in research and have less access to services. Cultural dissonance between Bangladeshi values and British norms, especially during the key developmental stage of 16–24 years, can intensify identity conflict and emotional distress. Despite these risks, uptake of talking therapies amongst this group remains low, potentially due to mistrust of formal services and reliance on informal support. This underutilisation of services highlights the need for culturally sensitive interventions that reflect the lived experiences of this population. Problem-solving therapy (PST), a structured, easily teachable cognitive-behavioural approach rooted in Lazarus and Folkman’s (1984) stress-coping model, offers a promising solution. PST promotes proactive coping by building stepwise problem-solving skills and has proven effective in diverse, low-resource settings. Its concreteness and flexibility appeal to youth, making it well suited for adaptation in high-income, multicultural contexts.

This study aims to culturally adapt a problem-solving intervention, originally developed in India, for British Bangladeshi youth through a participatory co-design process to improve its relevance, accessibility, and acceptability.

This study includes two co-design workshops with 32 British Bangladeshi youth (aged 16–24) to ideate and test the intervention, with prototyping taking place between the two workshops. The first workshop (ideate phase) was carried out (April 2025), involving seven focus group discussions with young people, generating key insights and ideas for the intervention. The ongoing (summer 2025) prototype phase involves iterative development of intervention materials in collaboration with a youth co-researcher. The user testing phase, scheduled for later in 2025, will assess the acceptability and usability of the prototype through further focus groups and observations.

Using the Ecological Validity Model (EVM), adaptations were identified across all eight dimensions: culturally appropriate language; preferred types of counsellor; culturally resonant metaphors; content grounded in lived experience; cultural framing of mental health and problem-solving steps; outcomes aligned with PST goals; delivery strategies suited to youth needs; and relevant community settings. These insights are shaping the intervention prototype.

This study shows how a problem-solving intervention can be co-designed with young people using participatory methods. It will yield a culturally tailored intervention for British Bangladeshi youth, with potential to increase engagement with evidence-based mental health support.

None Declared

Problematic Internet Use (PIU) is an increasing mental health concern, particularly among adolescents, and is associated with anxiety, depression, and impaired functioning. Emotional intelligence (EI) may serve as a protective factor, while physical activity (PA) supports psychological well-being. This study examined the relationships among PIU, psychological distress, EI, and PA across adolescents and adults.

This study aimed to (1) investigate associations among PIU, psychological distress, EI, and PA, and (2) compare patterns of vulnerability and protective factors between adolescents and adults.

A cross-sectional design was employed. Standardized self-report instruments were used: Kessler Psychological Distress Scale (K6) for psychological distress, Quality of Life Scale (QOLS) for well-being, Internet Addiction Test (IAT) by Young for PIU, Rapid Assessment of Physical Activity (RAPA) for PA, and an Emotional Intelligence Scale for EI. Descriptive statistics, correlation analyses, and group comparisons were conducted.

Among adolescents, 65% engaged in at least 30 minutes of moderate-intensity activity five times per week, and 67% reported vigorous activity at least three times weekly, reflecting relatively high PA levels. However, 72% displayed moderate PIU tendencies, with frequent loss of control over online time and emotional reliance on internet use. Distress levels were elevated: over 60% reported frequent sadness, hopelessness, or insignificance, with 38% scoring in ranges indicating risk for functional impairment. EI scores were low to moderate, particularly in recognizing others’ emotions (mean = 1.95/5).

Adults reported 53% meeting PA guidelines but lower engagement in vigorous exercise. 58% displayed moderate PIU, particularly difficulty disconnecting and using the internet to escape negative emotions. Psychological distress remained moderate to high, with 45% frequently reporting sadness or worry. EI scores were slightly higher than in adolescents (mean total = 12.65/25), yet still indicated gaps in stress regulation and empathy.

Correlational analyses revealed:

• - PIU was positively associated with psychological distress (r ≈ 0.45, p < .01).

• - EI was inversely correlated with both distress (r ≈ -0.40) and PIU (r ≈ -0.38, p < .01), indicating its protective role.

• - PA was negatively correlated with distress (r ≈ -0.30) and PIU (r ≈ -0.25, p < .05), supporting its moderating function.

• - Adolescents showed stronger associations between low EI, high distress, and PIU compared to adults, highlighting developmental vulnerability.

PIU is linked to higher distress and lower EI, particularly in adolescents. PA emerged as a protective factor. Interventions promoting EI and regular PA may reduce maladaptive internet use and improve mental health outcomes.

None Declared

Priapism is a rare but potentially serious urological emergency, defined as a prolonged and painful erection unrelated to sexual stimulation. Although uncommon in children and adolescents, it can cause significant morbidity if not promptly recognized and treated. Among pharmacological causes, antipsychotics are relevant triggers, mainly due to alpha-1 adrenergic receptor blockade. In youth with Autism Spectrum Disorder (ASD), atypical antipsychotics such as risperidone, aripiprazole, and olanzapine are frequently prescribed for irritability and behavioral symptoms. Despite widespread use, reports of priapism in this population are scarce, limiting risk estimates and clear management guidance.

To present a case of antipsychotic-induced priapism in an adolescent with ASD and review available evidence on risk factors, management, and clinical implications.

Clinical information was obtained from medical records and caregiver interviews. A narrative literature review was conducted in biomedical databases using terms related to priapism, antipsychotics, children, adolescents and ASD.

A 16-year-old male with ASD, on long-term risperidone (4.25 mg/day), was prescribed olanzapine (2.5mg/day) for insomnia. Four days after daily use of olanzapine, he presented to the emergency department with priapism requiring surgical intervention. Both risperidone and olanzapine were discontinued, and aripiprazole plus benzodiazepines were initiated, leading to favorable clinical outcome without recurrence. Caregivers were counseled on warning signs and the need for urgent medical evaluation.

The literature indicates that priapism risk is linked to alpha-1 affinity: risperidone, quetiapine, ziprasidone, and chlorpromazine are considered higher-risk, while aripiprazole and olanzapine have lower but not negligible risk. Cases with risperidone have been reported even after long-term exposure or in combination with other psychotropics. Aripiprazole, due to its low alpha-1 affinity, is often viewed as a safer alternative. Reports emphasize that priapism can occur without immediate temporal association to treatment initiation, highlighting the need for continuous vigilance. Clinical monitoring should be proactive in ASD, given communication barriers that may delay detection. Professional guidelines stress education of caregivers and urgent referral to urology when symptoms arise.

Antipsychotic-induced priapism in adolescents with ASD is rare but clinically significant. The presented case illustrates the importance of early recognition, prompt discontinuation of the offending agent, and transition to lower-risk alternatives such as aripiprazole. Continuous monitoring, caregiver education, and collaboration between psychiatry, pediatrics, and urology are essential.

None Declared

Problematic media use (PMU) is increasingly recognized as a behavioral concern in children, often linked to behavioral management and a lack of alternative activities. Existing research largely derives from high-income countries, leaving significant gaps in low- and middle-income contexts. Sri Lanka, a lower-middle-income country (LMIC) with expanding digital access but restricted recreational resources, offers a distinctive setting to examine PMU. Understanding these patterns is essential for developing culturally relevant and context-specific interventions

This study aimed to compare PMU between children with psychiatric illnesses and their peers without psychiatric diagnoses, and to examine sociodemographic correlates of PMU, including parental education and household income.

A cross-sectional comparative study was conducted at Lady Ridgeway Hospital, Colombo, in 2023. Participants were children aged 4–11 years: the study group comprised those attending Child and Adolescent Mental Health Services (CAMHS), while age- and sex-matched children from the Outpatient Department (OPD) served as controls. PMU was assessed using the Problematic Media Use Measure (PMUM), alongside a parent-completed sociodemographic questionnaire. Exclusion criteria included severe medical comorbidity, intellectual disability, or lack of parental consent. Written informed consent was obtained in the two local languages, and ethical approval was secured from institutional review boards.

The sociodemographic profiles of the two groups were broadly comparable, with no significant differences in age, gender, ethnicity, parental education, or household income. The study group (n = 214) included 120 children with ADHD (56%), 50 with Autism Spectrum Disorder (23.4%), 25 with anxiety disorders (11.7%), and 19 with depression (8.9%). Treatment modalities included medication only (60.7%), behavioural therapy only (23.4%), and combined treatment (15.9%). The comparison group comprised children without psychiatric diagnoses (n = 200). The mean PMUM score in the study group was significantly higher (23.5 ± 5.8) than in the comparison group (18.2 ± 4.3). Children with ADHD lower household income and lower parental education were significantly associated with higher PMUM scores.

Neurodivergence and socioeconomic disadvantage are associated with higher PMU in children, underscoring the need for routine screening and family-focused interventions in these groups.

None Declared

Adolescent psychiatric inpatient units faced heightened service challenges during the COVID-19 pandemic, with rising admissions for deliberate self-harm (DSH) and suicide risk. Few studies have examined how systemic and contextual factors influenced risk within these units during the peak of service disruptions, and in the post-pandemic period.

This study presents a longitudinal analysis of incidents on an adolescent psychiatric inpatient unit in Sydney, Australia between January 2020 and December 2023. It aims to understand the effect of COVID-19 and associated practice changes on readmission and incident rates on the ward.

Poisson and binomial regression models tested temporal trends in DSH, aggression and absconding incidents across the study period. Patient-level (gender, age, admission history), ward-level (readmission rate, average length of stay, bed occupancy), and COVID-19 (community and ward lockdown status) variables were included.

Incident rates increased significantly over time, with the steepest rise observed for DSH, particularly among female patients and those with multiple admissions. A dose-response relationship emerged, with DSH incidents rising from 11% at first admission to 87% at nine or more readmissions. Aggression peaked during periods of strictest ward restrictions, while 28-day readmission rate was the strongest overall predictor of incident rate.

By leveraging COVID-19 restrictions as a naturalistic experiment, this study offers a rare temporal and contextualised insight into how systemic factors shape risk in inpatient settings. Findings suggest that loss of autonomy and community leave may increase aggression risk, and repeated admissions may signal escalating self-harm risk. The results underscore the need for further research and development of trauma-informed inpatient care models that support transition to community through flexible care planning and sustained post-discharge support.

None Declared

Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are increasingly recognised as neurodevelopmental conditions that frequently co-occur in paediatric populations, presenting significant diagnostic challenges. Research indicates a high frequency of this comorbidity, with overlapping symptoms hindering diagnosis and co-occurrence associated with greater functional impairment in children. Since both disorders typically emerge in early development, focusing on paediatric populations is essential to ensure timely identification and intervention. Epidemiological data demonstrate considerable heterogeneity, highlighting the need to explicitly cite meta-analyses when reporting such rates. This highlights the need to clarify comorbidity and shared mechanisms in youth.

This systematic review examines current evidence regarding ADHD-ASD comorbidity prevalence, underlying aetiological mechanisms, and neurobiological foundations.

This literature review was conducted using PubMed databases and Virtual Health Library searches spanning 2020-2025, focusing on ADHD-ASD comorbidity. Search strategies employed “ADHD”, “autism spectrum disorder”, and “comorbidity” using Boolean operator AND. Studies met inclusion criteria if they: (1) included paediatric samples, (2) were published in English or Portuguese, and (3) addressed prevalence, aetiology, neurobiology, or therapeutic interventions. Exclusion criteria comprised case reports, editorials, and studies lacking mental health focus.

Autism spectrum disorder and ADHD represent neurodevelopmental conditions with prevalence rates of 1.5-2% and 5-9%, respectively, according to (Hatch et al. Psychol Sch 2022; 60:295-311). Comorbidity rates vary: 53-78% of children with ASD exhibit ADHD symptomatology, whilst 21% with ADHD display autistic traits. Both conditions demonstrate substantial heritability: ADHD shows 70-80% whilst ASD ranges 37-90%, with approximately 40% genetic overlap indicating shared mechanisms. Neuroimaging reveals overlapping dysfunction across attention networks and executive control systems. Children with both conditions experience greater functional impairments, higher anxiety, increased academic difficulties, and reduced therapeutic responsiveness. Environmental risk factors include maternal stress and toxin exposures. Effective approaches require comprehensive multimodal interventions combining behavioural and pharmacological therapies.

The substantial phenotypic and genetic overlap between ADHD and ASD necessitates integrated diagnostic frameworks recognising shared presentations and mechanisms. Given significant genetic convergence and overlapping neurobiological pathways, these conditions may be conceptualised as related spectrum disorders requiring specialised therapeutic approach. Comprehensive assessment and multimodal interventions remain essential for optimal outcomes.

None Declared

Cognitive impairments are observed in 75-80% of people with Schizophrenia, with a significant impact on everyday functioning, quality of life, treatment adherence, costs of care and rehabilitation outcomes.

The primary objective is to examine the efficacy of the combination of cognitive rehabilitation and pharmacological treatments with potential pro-cognitive action compared to stand-alone interventions. The next aims are to analyze the applicability context, the limitations of available scientific evidence and to determine future perspectives.

This study follows the guidelines of PRISMA Statement and of Cochrane Collaboration. The systematic research was conducted on electronic databases: PubMed, PsychINFO, Scopus, Cochrane CENTRAL. English, peer-reviewed papers were selected. A manual search was performed on Google Scholar. At least two revisors examined independently all papers. Methodological quality of included studies was evaluated using Clinical Trial Assessment Measure (CTAM). Inclusion criteria: randomized controlled trials (RCT) with baseline and at post-treatment outcome assessments, regardless of setting or duration; patients with diagnosis of Schizophrenia spectrum disorders, clinically stable and stabilized on antipsychotic therapy; combination of a cognitive rehabilitation intervention with a molecule with pro-cognitive function, tested against control groups treated with cognitive rehabilitation or with pro-cognitive molecules administered as stand-alone treatments; evaluation of efficacy on cognitive functioning, on psychosocial functioning and clinical symptoms, with validated assessment measures.

3126 studies were identified through electronic databases, 2073 excluding duplicates. 143 articles were identified with other resources. Totally 2216 papers were screened, 98 were examined and 25 papers related to 20 studies were included. Molecules investigated: atypical antipsychotics, d-serine, d-cicloserine, oxiytocin, modafinil, nicotine.

This review shows that available data are limited to specific settings of care and this might affect the results. The efficacy of combined cognitive rehabilitation and specific molecules on clinically stable individuals with schizophrenia is largely inconclusive. However, this issue is scientifically and clinically a topic of interest, warranting further research.

A. Ceraso: None Declared, R. Alberti: None Declared, R. Virgillito: None Declared, M. Fiore: None Declared, A. Rajkovic: None Declared, F. Coronelli: None Declared, E. De Leo: None Declared, S. De Bellis: None Declared, L. Pascariello: None Declared, U. Battelino: None Declared, G. Nibbio: None Declared, G. Deste Consultant of: -, S. Barlati Consultant of: -, A. Vita Consultant of: -.

Knowledge on risk and protective factors for the long-term outcome of children and adolescents diagnosed with psychosis before age 18 (Early-Onset Psychosis, EOP) is essential to improve the outcomes in this patient group. Being in employment is a particular important outcome for individuals living with psychosis and for reducing the societal cost of illness. Identification of predictive markers for long-term occupational functioning can guide clinical practice and tailor treatment interventions to target modifiable predictors as well as strengthen the interventions for the patients at highest risk of poor outcomes.

To describe the long-term sociodemographic, functional, and clinical outcomes of EOP and healthy control (HC) participants, and explore predictors of occupational functioning.

The study sample consists of 205 participants with EOP and 199 HCs aged between 10 and 17 at baseline. Clinical baseline data were linked to register-based outcome data from the Danish National Registers a mean of 11 years (range 4.5 to 23.5 years) after baseline assessment. At baseline, parental socioeconomic status, psychosis symptoms, neurocognitive functioning, social functioning, and drug use were assessed. At follow-up, register-data on employment status, marital status, income, educational level, supported housing, psychiatric hospitalizations, somatic hospitalizations and deaths were retrieved, and compared for EOP and HC participants. Predictors of competitive employment were explored using univariable and multivariable logistic regression.

At follow-up participants were between 18 and 41 years of age. Register-based outcomes showed markedly poorer sociodemographic, functional, and clinical outcomes for individuals with EOP compared to HCs. At follow-up 47% of EOP and 94% of HC participants were in competitive employment. Being in competitive employment at follow-up was in univariable analyses predicted by higher household income and better neurocognitive functioning (estimated IQ; verbal fluency; and attention and information processing speed) at baseline. These baseline measures did not remain significantly associated with competitive employment in multivariate analyses.

The finding that almost half of individuals with EOP was in employment at follow-up is encouraging compared to previous literature. The study nonetheless emphasizes the importance in continuous efforts to improve outcomes in early-onset psychosis, as outcomes across sociodemographic, functional, and clinical outcomes remains significantly poorer than controls. The study points to neurocognitive functioning as a potential modifiable treatment target to improve occupational functioning.

None Declared

Paliperidone palmitate 6-month (PP6M), 3-month (PP3M), and 1-month (PP1M) formulations have demonstrated efficacy in improving clinical outcomes and reducing risk of relapse in patients with schizophrenia. Real-world studies have shown that longer dosing intervals are associated with improved clinical outcomes, however, there is minimal evidence comparing the outcomes of these three formulations in clinical practice.

This study evaluated the effectiveness of PP6M vs PP3M and PP1M in delaying and preventing relapse among patients with schizophrenia and compared healthcare providers’ treatment satisfaction and healthcare utilization with longer dosing formulations.

Patient data (n=125) were collected using the MeMind digital ecosystem, covering the period from July 2014 to July 2024 across multiple hospitals in Madrid. Memind registry is representative of the population with schizophrenia that is attended in the participating hospitals. Given the fact that all-registered patients meeting eligibility criteria will be included, sample size estimation is not needed. The number of patients in treatment with PP6M is around 300.Two retrospective treatment phases were considered: one year of prior treatment with PP1M, PP3M, or a combination of both before initiating PP6M, and one year following the initiation of PP6M (1 year mirror image analysis). A Shapiro-Wilk test was performed to assess the normality of the distribution of differences. If the distributions were normal, paired t-tests were conducted to compare the matched cohorts (PP1M vs. PP6M and PP3M vs. PP6M). If the distributions were not normal, a Wilcoxon signed-rank test (nonparametric) was used.

The relapse rate during the PP1M–PP3M period was 9.6% (95% CI: 5.49–16.2), which was almost than double that observed during the PP6M period (4.8%; 95% CI: 1.05–8.55). The hazard ratio for relapse during the PP1M–PP3M period, compared to the PP6M period, was 2.07 (95% CI: 0.78–5.53). 34% of the patients were in monotherapy with PP1M, 49% with PP3M, and 53% with PP6M. The average satisfaction of psychiatrists with paliperidone palmitate long acting injectables was higher than 7.7 out of 10. Fewer visits to psychiatrists were required with PP6M treatment compared to PP1M and PP3M (p<0.001); attendance rates were almost 100%, and visits to mental health nurses’ offices also improved.

Paliperidone palmitate long-acting injectable formulations have shown low relapse rates in real-world settings, with PP6M demonstrating the lowest relapse rate. Combined with high treatment satisfaction and more efficient resource utilization, PP6M may enhance mental health service delivery for patients with schizophrenia.

E. Baca-Garcia Grant / Research support from: Janssen, Consultant of: Janssen, A. SERRA SEGURA Employee of: Johnson &Johnson, P. LOPEZ RENGEL Employee of: Johnson &Johnson, J. MEHAWEJ Employee of: Johnson &Johnson, J. ANTUNES Employee of: Johnson &Johnson Innovative Medicine, L. KILLION Employee of: Johnson &Johnson Innovative Medicine.

Schizophrenia is a chronic and severe psychiatric disorder characterized by relapses. Non adherence to medication is a major concern, with rates reported between 40% and 50%. Poor adherence is associated with relapse, increased hospitalizations, and a higher risk of suicide (Vega et al., Compr Psychiatry 2021;108:152240). Both direct (drug or metabolite measurement in biological fluids) and indirect methods (tablet counts, electronic monitoring, pharmacy records, etc.) have been used to assess adherence. However, research on biological markers of adherence remains scarce.

The aim of this study was to investigate whether serum interleukin-6 (IL-6) levels differ according to antipsychotic treatment adherence.

The sample included 43 patients who met ICD-10 criteria for paranoid schizophrenia and were in an acute psychotic phase. Blood samples were collected on the first day after admission at 12:00 h and 00:00 h by venipuncture. All patients were receiving antipsychotics due to clinical decompensation. Most patients (N = 15; adherence in the rest unknown) were admitted after treatment discontinuation, while a small subsample presented irregular adherence. Only a minority were strictly adherent (N = 7).

IL-6 was measured using ELISA techniques (Kikugawa et al., Anal Biochem 1992;202:249–55). Patients were treated in the Emergency Department of the University Hospital of the Canary Islands for acute psychotic decompensation and were admitted to the acute psychiatric unit between January 1 and June 1, 2006. Most patients were referred by Mental Health Units, family members, or emergency services; a small percentage (3.7%) presented on their own initiative. Informed consent was obtained either from the patient or, in cases of severe clinical status, from family members.

Comparisons between quantitative variables were performed using Student’s t-test for independent samples.

Serum IL-6 levels at 12:00 h on the day after admission were 0.39 (SD missing), while IL-6 levels at 00:00 h were 0.20 (SD missing).

Next table shows the comparison of serum IL-6 at 12:00 h and 00:00 h between adherent and non-adherent groups.Table 1.

Serum IL-6 levels at admission did not differentiate between patients who adhered to treatment and those who did not.

None Declared

Individuals with schizophrenia face approximately 2.5 times higher all-cause mortality and nearly twice the risk of cardiovascular disease(CVD)-related mortality compared to the general population (Correll et al. World Psychiatry 2022; 21:248–271).Aerobic fitness is defined as the ability of the circulatory and respiratory systems to supply oxygen to skeletal muscles during sustained activity (Franklin et al. Am J Prev Cardiol 2022; 12:100424).Low aerobic fitness is a strong, independent predictor of both CVD and mortality, with prognostic value comparable to diabetes and other established risk factors(Kodama et al. JAMA 2009; 301:2024–2035).In schizophrenia, poor aerobic fitness is also associated with clinical outcomes such as increased illness severity, particularly negative symptoms, and decreased global functioning(Vancampfort et al. J Ment Health 2015).Improving aerobic fitness thus represents a key target for reducing cardiometabolic risk and illness burden.

Given the limited and inconclusive data, this study aims to compare aerobic fitness between individuals with schizophrenia and healthy controls to determine whether patients with schizophrenia are at greater cardiovascular risk, and to explore its relationship with illness severity.

The study included 58 participants:29 individuals with schizophrenia and 29 healthy controls.All participants underwent a cardiopulmonary exercise test (CPET) using a cycle ergometer to assess aerobic capacity.Maximal oxygen consumption (VO₂max) was measured via respiratory gas analysis.For participants who did not reach VO₂max, the highest achieved value (VO₂peak) was recorded, and VO₂peak/max/kg was used to define exercise capacity.Symptom severity in patients was assessed using the Positive and Negative Syndrome Scale (PANSS).Group differences in exercise capacity were analyzed using the Mann–Whitney U test, and correlations between PANSS scores and aerobic capacity were examined by Spearman’s test.

Aerobic fitness (VO₂peak/kg) was significantly lower in the schizophrenia group compared to healthy controls(p= .001). No statistically significant correlation was found between VO₂peak/kg values and total PANSS scores,which reflect illness severity, in the schizophrenia group(p= .666). Similarly, no significant associations were observed between VO₂peak/kg and the PANSS subscales, including positive symptoms (p= .089), negative symptoms (p= .623),or general psychopathology scores(p= .962).

Individuals with schizophrenia demonstrated significantly lower aerobic fitness than healthy adults, confirming a substantial cardiorespiratory fitness deficit in this population. While no significant association was observed between aerobic fitness and symptom severity, this may reflect the possibility that these domains are not directly related in clinically stable patients.

None Declared

Schizophrenia (SCZ) is a severe disorder with partially understood pathophysiology. The early stage is crucial for understanding pathogenic mechanisms and improving treatment strategies. Anandamide (AEA), a neurotransmitter of the endocannabinoid system, may be protective against psychosis.

This study aimed to measure serum AEA levels in first-episode psychosis (FEP) at admission (T0) and remission (T1), compare them to healthy controls and explore clinical and inflammatory correlates of AEA levels

In a longitudinal observational study (Nov 2021–Dec 2023), 69 FEP patients and 74 controls underwent sociodemographic, clinical, psychometric assessment (PANSS, GAF, CGI, CAST) and blood tests (high sensitivity-CRP (hs-CRP), AEA, metabolic parameters).

Patients were predominantly young, single men, with high unemployment; one-third used cannabis. At T0, AEA levels were significantly higher in patients than in controls (p = 0.045) and remained stable at T1. AEA showed consistent negative correlations with all PANSS subscales (e.g., total PANSS at T0: r = −0.45, p<0.001; T1: r = −0.41, p=0.034),and CGI-severity scale (At T0: r = −0.316, p = 0.008). Its elevation was independent of cannabis use, and its association with FEP persisted after adjustment (OR = 3.54, 95% CI = 1.32–9.46; p = 0.012). A positive correlation with hs-CRP was observed at T0 (r = 0.24, p = 0.048), independent of other confounding factors such as smoking and metabolic parameters.

AEA is elevated in FEP, inversely associated with symptom severity and positively correlated with inflammation, suggesting a potential neuroprotective and anti-inflammatory role. The endocannabinoid system may represent a promising target for novel therapeutic strategies.

None Declared

PP3M has been proven to reduce relapse risk, hospital admissions and days spent in hospital in patients with schizophrenia, but there is little real-world evidence on patient acceptability and experience.

To assess patients’ experience, preferences, tolerability with PP3M compared to the monthly formulation (PP1M).

We distributed a 10-item questionnaire to adults on PP3M in community teams in four South London boroughs between July 2024 and March 2025. The domains covered were helpfulness, side effects, injection pain, service contact, and preferred dosing intervals. Descriptive analyses (percentages, non-parametric tests) were conducted via SPSS v29.

68 of 172 eligible patients responded (39.5%). 75% rated PP3M as “very” or “extremely” helpful; 84% preferred PP3M over PP1M, mostly citing convenience (62.9%) followed by medication efficacy (22.9%). Injection pain was mild or absent in 65.1%. When asked to describe their experience of adverse effects, 58.7% reported none, 25.4% reported experiencing some but they were not troubling, 11.1% had somewhat troubling and 4.8% reported unbearable adverse effects. No new adverse effects with PP3M were reported by 80.6%. Mental health service contact remained unchanged for 55.6%, while 31.7% reported more contact and 12.7% reported less contact. For preferred dosing interval, 64.5% preferred 3-monthly dosing; 33.9% would prefer 6-monthly, 1.6% would prefer 1-monthly dosing and 0% preferred one- or two-weekly interval.

Patients on PP3M report high acceptability, greater tolerability and strong preference for PP3M. Stable patients on PP1M should be offered the option to change to 3-monthly or 6-monthly paliperidone.

I. Clark Speakers bureau of: honoraria from Jannsen for presentation delivery, S. Gee: None Declared, D. Taylor Shareholder of: Myogenes, Grant / Research support from: Janssen, Recordato, Speakers bureau of: Janssen, Recordati, Sunovion, Otsuka.

Schizophrenia is a chronic severe mental illness affecting 24-million people globally, associated with a life expectancy 15 years shorter than the general population. Approximately 70% of people with schizophrenia experience auditory verbal hallucinations (AVHs), i.e. ‘hearing voices’. Current treatment approaches remain unsuccessful at treating AVHs in up to 30% of cases.

This systematic review and meta-analysis evaluated randomised controlled trials (RCTs) of potential non-pharmacological treatments for AVHs in schizophrenia spectrum disorders. The effectiveness of emerging treatments was assessed and gaps in research were identified, with implications for clinical practice.

A literature search was performed between 2013-2024 across five databases: PubMed, Embase, PsycINFO, Medline, and Web of Science. The meta-analysis included 45 studies, based on predefined criteria and an assessment for bias. Effect sizes (Hedge’s g) were calculated for each study and overall, using a random effects model with 95% confidence intervals. The study was conducted in accordance with PRISMA guidelines and was pre-registered (PROSPERO ID: CRD42024598615).

Our sample included 2,314 patients and fourteen different interventions. The calculated overall mean effect size for all interventions was -0.298 (95% CI, [-0.470,-0.126]), representing a medium size and statistically significant effect. Subgroup analyses revealed that both AVATAR therapy and cognitive behavioural therapy (CBT) subgroups had medium size and statistically significant effects. Conversely, repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) showed small size and not statistically significant effects.

AVATAR therapy has the strongest evidence for treating AVHs, highlighting the need for large-scale RCTs and consideration for integration into treatment guidelines. CBT requires standardisation in methodology for reliability, and clinical guidelines should focus on symptomology rather than diagnosis. Acceptance and commitment therapy shows promise but requires further high-quality RCTs. Non-invasive brain stimulation techniques require further trials before they can be considered for clinical use.

None Declared

Schizophrenia is a heterogeneous mental disorder with diverse clinical and biological profiles. Current diagnostic systems relying solely on symptoms may overlook the full diversity of patients’ presentations, so developing neurobiological subtypes has been of great interest in recent research (Clementz et al. Schizophr Bull 2022; 48 56-68).

Biomarkers such as inflammatory markers (Lalousis et al. Brain Behav Immun 2023; 113 166-175), features of metabolic syndrome (Saccaro et al. Front Psychiatry 2024; 15 1225693), and gut-brain axis indicators (González-Blanco et al. Eur Psychiatry 2024; 67(1) e84) provide insights into pathophysiology and could enhance precision psychiatry approaches.

To stratify schizophrenia patients into subgroups based on inflammatory, metabolic, and gut-brain biomarkers. To investigate associations of such profiles with clinical outcomes, including symptom severity and cognitive performance.

Data from 199 patients diagnosed with schizophrenia (DSM-5) (mean age 40.9 years, 60.3% male), enrolled in an observational, cross-sectional, multicentre study from four centres in Spain (PI17/00246) were analysed.

Assessment:

Biomarkers:

Inflammatory: C-reactive protein (CRP; mg/L).

Metabolic: Abdominal circumference (cm)

Gut-brain axis: Lipopolysaccharide-binding protein (LBP; μg/mL).

Psychometrics: CGI-SCH, Screen for Cognitive Impairment in Psychiatry (SCIP), Positive and Negative Syndrome Scale (PANSS) for Schizophrenia.

Statistics:

Models based on latent profile analysis (LPA) with 1 to 6 profiles were estimated and compared using AIC, BIC, entropy, and the bootstrap likelihood ratio test (BLRT).

Differences in cognitive tests (SCIP) and symptom severity (PANSS, CGI-SCH) were assessed by ANCOVA (controlled by age). Analyses were conducted in R.4.5.1 (package: tidyLPA)

A two-profile solution (AIC = 1555, BIC = 1588, entropy = 0.930, BLRT < 0.01) was selected as optimal for balancing fit, parsimony, and clinical interpretability. Two distinct biomarker profiles emerged: a normative profile (91.5% of participants) with typical biomarker levels, and a high-risk profile (8.5%) with elevated inflammatory and metabolic markers (see profiles’ representation in image 1).

The high-risk group showed significant impairments in working memory and verbal fluency compared to the normative group (see comparison in figure 2); no significant differences were found in PANSS or CGI-SCH scores.Image 1:

Integrating inflammatory, metabolic, and gut-brain biomarkers via LPA identifies distinct schizophrenia patient subgroups. The high-risk profile is associated with cognitive deficits despite comparable symptom severity. These findings support biomarker-informed precision psychiatry for targeted treatment approaches.

None Declared

Negative symptoms (NS) are central to schizophrenia, markedly impairing functioning and quality of life. Predominant, persistent NS, more severe than positive symptoms and difficult to treat, pose a particular challenge. Amisulpride and cariprazine are currently the main pharmacological options highlighted for primary NS treatment.

To analyse the effectiveness of cariprazine after amisulpride treatment in patients with predominant negative symptoms in two real world studies.

The Slovakian (SK) study was a 1-year-long, multicentric cohort study. The Latvian (LV) study was a 16-week, observational study assessing the effectiveness of cariprazine. In both studies adult schizophrenia outpatients who exhibited predominant negative symptoms according to clinical judgement were included. The primary outcome measure in the LV study was the Short Assessment of Negative Domains (SAND), an anamnesis-based scale that is composed of 2 positive items (delusions and hallucinations) and 5 negative items (anhedonia, alogia, avolition, asociality and affective flattening). Each item is rated from 0 to 6 (from not observed to extreme). In the SK study a modified version of the SAND (m-SAND) was used; items were rated from 1 to 6 with no ‘minimal’ option present. In addition, in both studies, the Clinical Global Impression Severity (CGI-S) was utilized. In this post-hoc analysis, mean differences from baseline were calculated with p-values identified with two sample t-tests.

In total, 12 patients from the LV study and 11 patients from the SK study were identified as switching from amisulpride to cariprazine. The mean age of patients were 41.4 years (SK) and 34.3 years (LV). All identified patients in the LV study were male, whereas 55% of patients in the SK study was female. The mean duration of illness ranged from 9.6 years (LV study) to 16.2 years (SK study).

The mean change from baseline in the SAND total score over 16 weeks was −5.5 (p = 0.01) in the LV study, indicating statistically significant improvement in NS. Nonetheless, this was not reflected in the CGI-S results (mean change from baseline = −0.7; p = 0.09).

The mean change from baseline in the m-SAND total score over 52 weeks was −12.3 (p < 0.001) in the SK study, indicating statistically significant improvement in NS. This was also apparent in the CGI-S (mean change from baseline = −1.9; p < 0.001).

In conclusion, NS seem to improve further with cariprazine after amisulpride treatment.

J. Dragašek Speakers bureau of: Gedeon Richter, Z. Dombi Employee of: Gedeon Richter Plc, P. Herman Employee of: Gedeon Richter Plc, R. Csehi Employee of: Gedeon Richter Plc, Á. Barabássy Employee of: Gedeon Richter Plc, E. Rancans Grant / Research support from: Gedeon Richter, Janssen Cliag, Lundbeck, Consultant of: AbbVie, Gedeon Richter, Janssen Cliag, Lundbeck, Servier, Speakers bureau of: AbbVie, Gedeon Richter, Grindex, Janssen Cilag, Lundbeck, Servier, Zentiva

TV-44749 is an investigational, long-acting, subcutaneous (SC) formulation combining olanzapine (OLZ) and an innovative copolymer-based drug delivery technology in a long-acting injectable (LAI) suspension intended to address the limitations of oral and intramuscular OLZ. Phase 1 trial results showed that TV-44749 exhibited a favorable extended-release pharmacokinetic (PK) profile and that once-monthly doses of 318, 425, and 531 mg yield comparable OLZ exposures corresponding to oral daily doses of 10, 15, and 20 mg, respectively. These results guided dose selection for the phase 3 SOLARIS trial (NCT05693935) in adults with schizophrenia (SZ). Through the double-blind, placebo-controlled, acute treatment phase (Period 1) of SOLARIS, all three TV-44749 doses resulted in significantly greater efficacy. The long-term safety data from SOLARIS (Period 2) demonstrated that TV-44749 was generally well tolerated. Across the clinical development of TV-44749, no suspected or confirmed post-injection delirium/sedation syndrome (PDSS) events were reported (3990 TV-44749 injections).

The primary objective of the ORBIT trial is to assess the relative bioavailability of TV-44749 compared with EU-registered oral OLZ in adults with SZ, and support PK bridging between the two formulations. Secondary objectives include additional PK, safety, and tolerability endpoints. Trial design was based on the European Medicines Agency guidelines (Document: EMA/CHMP/EWP/280/96 Rev1) and TV-44749 phase 1 PK trial results.

ORBIT is an ongoing phase 1, 21-week, multicenter, open-label, multiple-dose, single-sequence trial in people living with SZ (NCT06315283). Adults (aged 18–64 years) clinically stable on oral OLZ 20 mg/day over ≥4 weeks before screening and not currently on other antipsychotic treatments were recruited in the US and EU. In treatment Period 1, participants receive oral OLZ 20 mg daily for 7 days. Treatment Period 2 comprises three TV-44749 531 mg once-monthly administrations. The primary endpoint is the OLZ exposure ratio between TV-44749 and oral OLZ administration over a 28-day dosing interval. Secondary endpoints include minimum plasma concentration at end of dosing interval and maximum observed plasma drug concentrations for both treatments. Safety and tolerability are also being assessed.

Recruitment is complete, with anticipated trial completion by September 2025.

When completed, ORBIT trial results will add to the body of evidence, including modeling and simulation, to support establishing a PK bridge between TV-44749 and oral OLZ, and provide additional PK, safety, and tolerability data. TV-44749 may become the first LAI OLZ formulation that avoids the Risk Evaluation and Mitigation Strategy (REMS) associated with PDSS in adults with SZ.

A. Merenlender Wagner Employee of: Teva, K. Shulman Shareholder of: Teva, Employee of: Teva, R. Gidron-Budovsky Employee of: Teva, A. Elgart Shareholder of: Teva, Employee of: Teva, A. Jehassi Employee of: Teva, N. Sharon Employee of: Teva, R. Apolinario Shareholder of: Teva, Employee of: Teva, G. Davis Shareholder of: Teva, Employee of: Teva, K. Duma Employee of: Teva, M. Suett Shareholder of: Teva, Employee of: Teva, D. Gutman Shareholder of: Teva, Employee of: Teva, L. Rabinovich-Guilatt Employee of: Teva

Achieving a favourable functional outcome is significantly influenced by neurocognition. A previous pilot study investigated whether cognitive dysfunction improves during inpatient treatment, in which acutely admitted patients receive a combination of pharmacological treatment and cognitive remediation (Maihofer et al. J Clin Med 2024, 13, 4843).

The present study aims to investigate the extent to which the functional outcome of patients diagnosed with psychotic and affective disorders is associated with cognitive function over time.

This ongoing study employed the Screen for Cognitive Impairment in Psychiatry (SCIP-G: Sachs et al. Schiz Res Cogn 2021, 25, 100197; Sachs et al. Schiz Res Cogn 2022, 29, 100259) to evaluate 311 psychiatric inpatients aged 18–66 years (181 female, 130 male). The International Classification of Diseases, Tenth Revision (ICD-10) research criteria were used to determine patient diagnoses in this study. 105 patients were diagnosed with F2 (schizophrenia, schizoaffective and delusional disorders), 40 patients met the criteria for bipolar mania, 39 for bipolar depression and 127 patients met the criteria for unipolar depression (F32/F33). All patients received state-of-the-art pharmacotherapy and cognitive remediation using the COGPACK® software package version 6.06. Functioning was assessed using the Global Assessment of Function (GAF).

A significant difference was found in SCIP scores between time points 1 and 2 (F = 175.8, p < .001). Furthermore, significant improvement was observed in all four diagnostic groups (p < .001). There was no significant interaction between time and diagnosis, indicating that cognitive abilities improved significantly in all groups, with similar trends observed over time. A significant interaction effect was found between SCIP and GAF scores at both time points (p < .044). This is consistent with the idea that better cognitive performance is associated with a better functional outcome. No significant effect of diagnosis group was found (GAF/SCIP x diagnosis, p = .193).

Cognitive dysfunction is commonly found in people with psychiatric disorders and can easily be assessed during an inpatient hospital stay with the SCIP. Treatment in an inpatient setting, which includes pharmacotherapy and cognitive training, improves cognitive deficits and overall functioning. Improvement in cognitive performance is observed to a similarly high degree in patients with psychotic disorders, bipolar disorder and depression.

None Declared