Zuranolone (ZRN) is a positive allosteric modulator of both synaptic and extrasynaptic gamma-aminobutyric acid type A receptors and a neuroactive steroid approved as an oral, once-daily, 14-day treatment course for adults with postpartum depression in the US and under investigation for adults with major depressive disorder (MDD). The randomised, double-blind, placebo-controlled, Phase 3 CORAL Study assessed the efficacy and safety of ZRN 50 mg vs placebo, each co-initiated with an open-label standard-of-care antidepressant (ADT). Patients who completed CORAL could roll over into open-label SHORELINE, which assessed the safety and tolerability of ZRN 50 mg and need for repeat treatment courses in adults with MDD.

To assess the safety and tolerability (primary endpoint) and need for repeat ZRN 50 mg treatment courses (secondary endpoint) in adults with MDD who previously enrolled in CORAL.

CORAL enrolled adults (18–64 years) with MDD and 17-item Hamilton Rating Scale for Depression (HAMD-17) total score ≥24. After completing the 6-week CORAL Study, patients who enrolled in SHORELINE could enter a 46-week observation period to assess the safety and need for 14-day repeat ZRN treatment course(s), with a total of ≤4 repeat treatment courses permitted. Patients were screened every 2 weeks with the 9-item Patient Health Questionnaire, and scores ≥10 prompted a HAMD-17 assessment within 1 week. Patients with HAMD-17 total score ≥20 were eligible for repeat ZRN course(s) ≥8 weeks after completing the prior ZRN treatment course.

Among the 190 patients from CORAL who rolled over into SHORELINE and received ≥1 ZRN treatment course in either study, 133 (70.0%) had received ZRN+ADT and 57 (30.0%) received placebo+ADT in CORAL. Overall, 118 rollover patients received ≥1 open-label ZRN treatment course in SHORELINE. For patients who received ≥1 ZRN treatment course in either study, 76.8% received 1 (54.2%; 103/190) or 2 (22.6%; 43/190) total ZRN treatment courses across both studies in up to 1 year in study. The most common (>5%) treatment-emergent adverse events (TEAEs) during treatment and 14 days following the last ZRN dose were somnolence (16.1% of patients), dizziness (8.5%), headache (8.5%), fatigue (7.6%), sedation (5.9%), and nausea (5.1%); study-period TEAEs (73.7%; 87/118) for the majority of patients were mild/moderate (69.5%; 82/118) in severity and occurred primarily during the treatment period (58.5%; 69/118). No signals for increased suicidal ideation/behaviour were observed.

Safety and tolerability among rollover patients were consistent with previous studies; most of the TEAEs reported by adults with MDD who received ZRN were mild/moderate in severity. Most patients who rolled over from CORAL to SHORELINE received ≤2 total treatment courses in up to 1 year in study.

G. Mattingly Grant / Research support from: Akili, Alkermes, Allergan (now AbbVie), Axsome, Boehringer, Janssen, Lundbeck, Medgenics, NLS-1 Pharma AG, Otsuka, Reckitt Benckiser, Roche, Sage, Sunovion, Supernus, Takeda, and Teva, Consultant of: Akili, Alkermes, Allergan (now AbbVie), Axsome, Ironshore, Intra-Cellular Therapies, Janssen, Lundbeck, Neos Therapeutics, Otsuka, Purdue, Rhodes, Sage, Sunovion, Takeda, and Teva, Speakers bureau of: Alkermes, Allergan (now AbbVie), Ironshore, Janssen, Lundbeck, Otsuka, Sunovion, and Takeda, S. Mathew Grant / Research support from: Biohaven Pharmaceuticals, Boehringer-Ingelheim, Janssen, Merck, Sage Therapeutics, Inc., and VistaGen Therapeutics, Consultant of: Allergan (now AbbVie), Alkermes, Almatica Pharma, Axsome Therapeutics, BioXcel Therapeutics, Boehringer-Ingelheim, Clexio Biosciences, COMPASS Pathways, Eleusis, EMA Wellness, Engrail Therapeutics, Greenwich Biosciences, Intra-Cellular Therapies, Janssen, Levo Therapeutics, Perception Neurosciences, Praxis Precision Medicines, Neumora, Neurocrine, Relmada Therapeutics, Sage Therapeutics, Inc., Seelos Therapeutics, Signant Health, and Sunovion, S. Parikh Grant / Research support from: Aifred, Assurex, Janssen, Mensante, Sage Therapeutics, Inc., and Takeda, S. Aaronson Grant / Research support from: COMPASS Pathways and Neuronetics; has served as a consultant to Genomind, Inc., Janssen, LivaNova PLC, Neuronetics; and Sage Therapeutics, Inc., Speakers bureau of: Janssen and Sunovion Pharmaceuticals, Inc., B. Baune Speakers bureau of: Angelini, AstraZeneca, Biogen, Bristol Myers Squibb, Janssen, LivaNova, Lundbeck, Novartis, Otsuka, Pfizer, Servier, Sumitomo Pharma, Wyeth, and Boehringer-Ingelheim, A. Czysz Shareolder of: Sage Therapeutics, Inc., Employee of: Sage Therapeutics, Inc., I. Nandy Shareolder of: Sage Therapeutics, Inc., Employee of: Sage Therapeutics, Inc., V. Ona Shareolder of: Sage Therapeutics, Inc., Employee of: Sage Therapeutics, Inc., C. Brown Shareolder of: Sage Therapeutics, Inc., Employee of: Sage Therapeutics, Inc., S. Kyaga Employee of: Biogen Inc., F. Forrestal Employee of: Biogen Inc., S. Levin Employee of: Biogen Inc., J. Doherty Shareolder of: Sage Therapeutics, Inc., Employee of: Sage Therapeutics, Inc., G. Mattingly: None Declared

Depression is a major concern among homeless individuals. Studies link religiosity and spirituality (RS) with lesser depressive symptoms, but evidence is scarce among the homeless.

This study aims to assess the association between RS and depressive symptoms in homeless individuals in Brazil.

This cross-sectional study involved 456 homeless individuals in São Paulo, Brazil. It received approval from the Ethics and Research Committee of the Faculty of Medicine of Itajubá, Brazil. We used adjusted linear regression models to analyze the association between RS and participants’ depressive symptoms. Depressive symptoms were assessed with the Patient Health Questionnaire-9 (PHQ-9). We used the P-DUREL to measure religiosity, FACIT-Sp12 for spirituality, and the Brief-RCOPE scale for religious-spiritual coping strategies.

Out of 482 invited participants, 456 (94.6%) completed all questionaries, mostly males (75%) with an average age of 44.53 (SD 12.62) years. About 49.6% had depressive symptoms (PHQ-9 ≥10 points). After controlling for sociodemographic and health variables, factors such as temple/church attendance (≥ 3 times per month), increased religiousness (both organizational and intrinsic), positive religious/spiritual coping, and peace, faith and meaning were inversely related to depressive symptoms. Conversely, dysfunctional use of RS, such as in negative spiritual-religious coping strategies, correlated with heightened depressive symptoms.

High depressive symptom prevalence was found among Brazilian homeless individuals. Functional use of RS was negatively linked to depressive symptoms, while dysfunctional RS, like negative spiritual-religious coping strategies, correlated with higher depressive symptoms. These findings can aid healthcare professionals, particularly psychologists and psychiatrists, in addressing RS in the homeless population.

None Declared

Current treatment options for depression remain unsatisfactory. SAMe, a naturally occurring body chemical available as a dietary supplement, was discovered in the 1950s. SAMe deficiency is associated with depression.

This systematic review and meta-analysis aimed to investigate the efficacy and acceptability of SAMe in treating patients with depression. The primary efficacy outcome was measured through the reduction in depression severity scores. All-cause dropout rates were assessed as indicators of treatment acceptability.

To include the randomized trials comparing SAMe with other agents, we conducted a search on PubMed, Embase, and the Cochrane Library from their inceptions until April 27, 2023. The quality of trials was assessed using version 2 of the Cochrane risk-of-bias tool for randomized trials (RoB 2). Depression severity and overall dropout rates were synthesized using a random-effect model for frequentist pairwise meta-analysis.

We categorized 23 trials (N = 2,234) into 11 trials comparing SAMe vs. placebo, 5 trials comparing SAMe + antidepressant vs. placebo + antidepressants, and 7 trials comparing SAMe vs. antidepressants. SAMe demonstrated a significantly greater reduction in depressive symptoms compared to placebo (SMD = -0.58, 95%CI [-0.93; -0.23], I2 = 68%), as can be seen in Figure 1. A trend was observed wherein SAMe showed a lesser reduction in depressive symptoms compared to antidepressants (SMD = 0.06, 95%CI [-0.06; 0.18], I2 = 49%). When administered alongside ongoing antidepressant treatment, SAMe did not significantly differ from placebo in reducing depressive symptoms (SMD = -0.16, 95%CI [-0.44; 0.13], I2 = 57%). In the subgroup analysis of 11 trials comparing SAMe and placebo, it was found that while the intramuscular (SMD = -0.92, 95%CI [-1.39; -0.44]) and oral routes (SMD = -0.66, 95%CI [-1.24; -0.08]) revealed the efficacy of SAMe, the intravenous route did not exhibit the same efficacy (SMD = -0.16, 95%CI [-0.47; 0.14]). The efficacy of SAMe was not influenced by factors such as physical illness, history of antidepressant nonresponse, proportion of females, age, duration and dosage of SAMe supplementation, publication year, and baseline depression severity. There was no significant difference in dropout rates between SAMe and controls.

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Limited evidence suggests that SAMe is well accepted and effective in reducing depressive symptoms. However, its antidepressant effect may not be as strong as that of traditional antidepressants. Randomized-controlled trials comparing SAMe to antidepressants in depressed patients, both with and without ongoing antidepressant use, are still necessary.

None Declared

The American Academy of Pediatrics reports an incidence of 1 in every 54 children (Council on Children with Disabilities, 2021). The unique circumstances surrounding children born in 2020, who have experienced the COVID-19 pandemic since birth, present a distinct set of challenges for their neurodevelopmental well-being. The pandemic has led to reduced opportunities for learning and social interaction, masking mandates, decreased social support for research, and the potential misattribution of Autism Spectrum Disorders ASD symptoms to the effects of social isolation.

This study aims to develop such a program for children born during the COVID-19 pandemic (2020-2022).

All children born in March 2020 were included in the study. The initial assessment involved administering the ASQ-3 to evaluate their development across the specified domains. Diagnostic Evaluation: Among the population, 6% (4 children) displayed concerning signs on the ASQ-3, warranting further diagnostic evaluation by specialized health professionals for possible ASD.

Early Intervention and School Monitoring: Of the remaining 72% (46 children), who did not require diagnostic evaluation, intervention guidelines were provided, both within the school environment and at home. These children were reevaluated after a three-month period. Follow-up in the School Environment: Those children who underwent reevaluation were categorized into three groups: Nine children fell into the “gray” category on the ASQ-3 and were subsequently referred for diagnostic evaluation. Thirty-seven children progressed to the “white” category on the ASQ-3 after receiving intervention guidelines in both school and home settings. The findings of this research underscore the potential impact of the COVID-19 pandemic on the neurodevelopment of children born in 2020. 6% of the evaluated population were referred for diagnostic evaluation due to signs of ASD, suggesting a potential association between the pandemic and an increased risk of ASD within this cohort.72% of children who received intervention guidelines demonstrated significant improvements in their neurodevelopment, highlighting the critical role of early intervention and school-based monitoring

Implementing support strategies within educational settings was linked to positive developments in neurodevelopmental outcomes. Consequently, school-based neurodevelopmental monitoring, complemented by cohesive curricular guidelines, emerges as a beneficial approach for enhancing child development outcomes. The ASQ-3, as a structured instrument, proves invaluable in facilitating neurodevelopmental surveillance within educational settings, particularly in contexts with high demand and limited access to specialized care.

None Declared

Hospital nurses have played a crucial role during the covid-19 pandemic. Research demonstrates the extent to which nurses were experiencing acute stress and psychological distress during the waves of the pandemic.

The purpose of this study was to assess the psychological distress (stress, depression, and anxiety) of nurses working in public hospitals in Greece during the covid-19 pandemic, to identify their coping strategies, and to explore the eventual sociodemographic and work environmental influence on distress and the coping strategies.

Sample consisted of 317 nurses working in public hospitals. A self-report online questionnaire was used for data collection. The first part of the questionnaire comprised the Depression, Anxiety, and Stress Scale (DASS-21), the second part included the Greek version of the Ways of Coping questionnaire (WAYS), the third part the Oslo Social Support Scale (OSSS-3), and the fourth part included participants’ sociodemographic data. Analyses were conducted using SPSS statistical software (version 26.0).

18.4% of participants presented severe depression, 39.9% very severe anxiety, and 22.5% very severe stress. Significantly lower levels of depression, anxiety, and stress were experienced by those who slept more than 5 hours a day, compared to those who slept up to 5 hours. Participants who were infected with the coronavirus had significantly higher levels of depression, anxiety, and stress. Additionally, participants who received moderate/high social support experienced overall less anxiety, stress, and depression than those who received low social support. Finally, the more they sought social support to deal with their problems and the more they avoided stressful situations, the higher the levels of depression, anxiety, and stress.

A staff care protocol must be applied by every hospital, including rest breaks and night-shift naps, psychosocial support for those who get infected by SARS-CoV-2 and their families, peer support (groups and mentoring), and coping skills trainings.

None Declared

The northern region of Italy had been the epicenter of the first wave of Covid-19. The youth population residing in this area experienced an extended period of restrictive measures implemented to curb the spread of the virus. Given the adverse effects of social distancing and lockdown measures, there is a concern regarding the mental health of young individuals in this region. However, there remains a notable scarcity of studies exploring the long-term impact of the pandemic on the mental health of this vulnerable population.

To assess psychopathological symptoms among adolescents and young adults in order to evaluate the extent of their impact in the context of the Covid-19 pandemic. To explore potential risk factors and resilience factors in youth who have experienced the effects of the pandemic.

Two studies are performed. Study n1 has observational design and includes 7,146 adolescents and young adults (age range 14–25) evaluated during the fourth wave of the COVID-19 through standardized measures for depression, anxiety, anger, somatic symptoms, resilience, loneliness and post-traumatic growth. Study n2 has prospective design and includes 153 students (mean age 16.1±0.49), evaluated before the Covid-19 pandemic (November 2019–January 2020) and 1 year later (April–May 2021) to measure anxiety, depression, stress, emotional dysregulation, maladaptive behaviours.

Study 1. Clustering methods identifed two groups of students with different psychological features, that we further defined as “poor mental health” and “good mental health”. Those with poor mental health were characterized by higher scores of loneliness and self-harm, followed by being of female gender, presenting binge eating behaviors and, finally, having unsatisfying family relationships.

Study 2. Over the course of one year, significant changes in various psychological parameters were observed: an increase in anxiety, stress for future uncertainty, and higher frequency of maladaptive behaviours.Stress related to social domains (i.e., school attendance, romantic relationships, peer pressure) decreased over the year. Cluster analysis identified three distinct groups of youths based on their changes in psychopathological symptoms over time: those who worsened (N=23; 15%), improved (N=55; 34%), or remained stable (N=75; 46%). Furthermore, adolescents who reported an increase in self-harm (OR=2.61; p<0.001), binge-drinking (OR=3.0; p=0.007), aggressiveness (OR 1.92; p=0.004), and binge-eating (OR 2.55; p=0.003) were more likely to be associated with a worsened mental health condition.

The findings from these studies substantiated the significant psychological distress caused by the COVID-19 pandemic. Furthermore, they yielded valuable further insights regarding into the factors linked to distinct patterns of mental health outcomes.

None Declared

COVID-19 is a multisystem disease affecting not only the respiratory, gastroenterstitial and vascular systems, but also the central nervous system, which leads to a wide range of neurological and mental complications. 3 years of experience in combating the pandemic has shown that elderly people burdened with chronic somatic diseases are the most vulnerable risk group for the development of severe course and complications of COVID-19.

To study the impact of COVID-19 on the onset and course of mental illness in elderly inpatients

We examined 67 inpatients aged 50 to 95 years with various mental pathologies, who underwent COVID-19 from February 2020 to December 2021. 46 people had previous history of mentall disease (PHMD), in 21 cases the disease developed for the first time. Statistical analysis was performed.

In the manifest group of patients, depressive episodes predominated (42.9%), including psychotic episodes (9.5%). In 28.6% of cases, organic disorders were diagnosed in the form of emotional lability, organic depression, mild cognitive impairment and delirium. In 23.8% of patients, neurotic disorders were observed in the form of depressive reactions, panic and generalized anxiety disorder. In one case (4.8%), acute polymorphic psychosis with symptoms of schizophrenia was diagnosed. The PHMD group includes affective disorders - 45.7%; organic disorders, including dementia 26.1%; schizophrenic spectrum disorders -19.6% and neurotic somatoform disorders - 8.7%. In the acute and subacute periods of COVID-19, acute psychotic states (APS) developed in both groups of patients (in 23.3% and 30.4%, respectively) in the form of delirium, psychotic depression, or polymorphic psychosis. APS were more common in PHMD patients with organic (50%) and schizophrenic spectrum disorders (33.3%) with a predominance of delirium. In the long-term period of COVID-19, PHMD patients more often than non-PHMD (60.9% and 38.1%) developed cognitive impairment (CI), especially in schizophrenia-like (77.8%) and organic (83.3%) disorders. CI developed twice as often after APS (89.5% and 39.6%, p<0.001), reaching the degree of dementia in 15.8% of cases. APS were significantly associated (p<0.05) with the development of CI (0.567733), the age of patients (0.410696) and the presence of previous cerebrovascular insufficiency (0.404916).

The age-related features of the mental consequences of COVID-19 are the occurrence of APS in the acute period of infection and the deterioration of cognitive activity at a remote stage. The PHMD patients, especially with disorders of organic and schizophrenic spectrum, were found to be more vulnerable to the effects of COVID-19. In them, the occurrence of APS was a risk factor for the development of dementia, while in primary diseased, and patients with affective and neurotic disorders, CI was reversible or had the character of a mild cognitive disorder.

None Declared

The COVID-19 pandemic has had a profound impact on mental health worldwide because of complex societal disruptions and neuropsychiatric consequences stemming from SARS-CoV-2 infection. All age groups have been affected by this pandemic, with particular focus on the vulnerabilities faced by children and adolescents who have experienced multiple stressors. These stressors involve various emotional, physiological, and behavioral challenges stemming from different factors, such as mandatory social distancing due to school closures, increased parental stress caused by the incessant spread of the pandemic, severe trauma from losing family members, a surge in cyberbullying linked to higher online activity, and a worrying rise in unreported incidents of child abuse. Empirical reports document an increase in suicidal tendencies and suicide attempts among adolescents during this crisis.

This study conducted a comprehensive review of existing literature focused on the mental health of individuals aged 0-24 years in both pre-pandemic and pandemic eras. This study conducted comparative analyses to identify significant changes.

Adhering strictly to the PRISMA guidelines, we conducted comprehensive searches on Google Scholar and PubMed to identify peer-reviewed articles published in English.

Most studies revealed deteriorating mental health conditions among adolescents and young adults following pandemic onset. These conditions were characterized by high rates of depression, anxiety, and psychological distress. Furthermore, several studies have identified a notable increase in negative emotions and heightened feelings of loneliness. Primary school children experienced a decline in attention span, emotional regulation, hyperactivity, and enthusiasm for academic engagement.

Based on the analysis of data from both the pre-pandemic and pandemic periods, it is evident that the COVID-19 pandemic had a detrimental impact on the mental well-being of children and young individuals. Therefore, it is crucial to identify the risk factors and protective measures linked with pandemics to enhance mental health resilience and better equip societies to cope with future health emergencies and other crises.

None Declared

When patients in a closed hospital ward experience acute psychosis and become highly agitated or pose a risk to themselves and others, it’s often crucial to provide immediate sedative treatment. However, there is currently no consensus on whether the preferred medication for these situations should be antipsychotic drugs or benzodiazepines.

This study aimed to compare how well a single intramuscular dose of 2-4 mg Lorazepam performs against 40 mg Clothiapine in terms of effectiveness and side effects. These treatments were administered as immediate emergency measures to patients experiencing psychosis with severe agitation or behaviors that posed a risk to themselves or their surroundings.

We conducted a retrospective clinical study involving 100 patients experiencing aggressive psychosis. These patients were divided into two groups. The first group comprised 50 patients who received a single intramuscular (IM) dose of up to 40 mg Clothiapine. The second group consisted of 50 patients who received IM treatment with 2-4 mg Lorazepam. We assessed the patients’ outcomes around 8 hours after treatment or upon receiving any additional treatment.

There were no significant statistical differences in the demographic and clinical characteristics (e.g., age, gender, number of hospitalizations, duration of illnesses, psychiatric diagnosis, comorbidity) of the patients between the two groups (p > 0.05).

Before treatment, there were no statistical differences in the severity of clinical symptoms (CGI-S) between the two groups [CGI-S (Mean ± SD): 5.32 ± 1.09 vs. 5.38 ± 1.4, p = 0.8].

However, in the Clothiapine group, a statistically significant clinical improvement (CGI-I) was observed after treatment [CGI-I (Mean ± SD): 2.42 ± 0.9 vs. 1.96 ± 1.16, p = 0.029 *].

There were no significant differences in the need for physical restraint or additional medication following the initial treatment between the two groups (p > 0.05).

Furthermore, there were no statistically significant differences in the major side effects of the drugs, the necessity for referral to the general emergency room, or incidents of falls (p > 0.05).

When dealing with a psychotic state marked by severe agitation or threats to oneself and others, the use of IM Clothiapine as a treatment option may offer certain advantages over IM Lorazepam. Importantly, these advantages come without significant exposure to side effects or potential risks associated with Clothiapine.

None Declared

Numerous countries, notably within Europe, have sanctioned the practice of euthanasia. Extant legal frameworks meticulously define the extent, essence, and application of euthanasia, encompassing divergent characterizations, explications of entitlements, procedural modalities, and provisions for access. Nonetheless, the precise function of psychiatrists within these legislative contours remains conspicuously nebulous.

The present inquiry undertakes a comprehensive evaluative review of the euthanasia phenomenon vis-à-vis the intricate tapestry of European legislative paradigms, with an emphasis on elucidating the multifaceted involvement of psychiatry within this evolving landscape.

A nuanced narrative review is undertaken, encapsulating the contemporary state-of-affairs, fundamental conceptual architectures, the tenets of the Spanish Organic Law 03/2021, and the pharmaceutic armamentarium deployed in the orchestration of euthanasic practices. Additionally, the methodological blueprint employed within a prominent tertiary healthcare institution situated in Madrid is meticulously expounded.

To date, euthanasia has garnered legal imprimatur across diverse jurisdictions including, but not limited to, the Netherlands, Belgium, Colombia, Canada, Spain, and New Zealand. The ambit of assisted death and its application to the domain of mental infirmities is meticulously deconstructed. Within the overarching realm of foundational concepts, a rigorous delineation is rendered between euthanasia, medical succor in the throes of mortality, assisted self-termination, facilitated demise, provision of mortal release, judicious calibration of therapeutic enterprise, and the contours of palliative sedation. Distinction between the principal executor and the advisory consultant is rendered salient. The rubric of conscientious objection emerges as an inviolable entitlement of healthcare practitioners enmeshed in the provisionary matrix.

The enduring incumbency of the psychiatrist as a pivotal appraiser of cognitive and volitional faculties holds firm. The conspicuous influence of psychopathological constellations upon the contours of euthanasia eligibility precipitates cogent deliberation.

As the frontiers of euthanasia expand to encompass an augmented array of legal jurisdictions, this study underscores the increasingly intricate role inhabited by psychiatrists in the matrix of evaluative assessments. The proclivity of mental maladies to exert a substantial gravitational pull upon determinations of eligibility for euthanasia accentuates the exigency for refined explication of roles and responsibilities within this evolving sphere, a clarion call resonant not only within the precincts of psychiatry but reverberating across the broader firmament of medical praxis.

None Declared

The russian invasion in Ukraine has significantly affected the mental health (MH) of the local population while access to mental health support remains limited due to multiple reasons coming from both the provider and acceptor sides. The war obviously negatively impacts MH but has also paradoxically given an “open window” for shifting current practices both in the healthcare system and within society. Investigation of current people’s attitudes on this matter should be the primary step to address the issue and initiate any change.

5 main objectives identified to analyze within the convenience sample were: MH state and self-care behaviors during the full-scale invasion, MH stigma and self-stigma, intention to use professional MH support, beliefs on access to professional MH support, query to change current MH attitudes and practices.

This research was conducted using primary data collection. The online questionnaire consisted of 5 blocks and was designed based on PHQ-9, DASS-21, PCL-5, Brief-COPE and CAMI. 332 civilians underwent the survey in March-April 2023 and were divided by age, gender, location and situation; inclusion criteria were to be >16 y.o. being affected by war and capable of completing the survey in Ukrainian. Relevant ethical measures were applied. Descriptive and correlational analysis was used to analyze the data.

The majority of respondents rated their mental health as good. Anxiety was the most prevalent emotion, particularly among younger age groups. Different genders and age groups exhibited varying combinations of emotions, such as fatigue, peace, anger, sadness etc. Many participants felt self-reproach for not doing enough; coping strategies varied among age groups. Females were 8.14 times more likely to seek mental health support, and those inside Ukraine were 0.32 times less inclined. 66.2% never seek any MH services, with older men leading; only 8.7% consult specialists during crises, showing gender differences. Distrust in specialist qualifications is one of the barriers on access in people’s beliefs and is more prevalent among older generations. The absence of self-mental health stigma makes individuals 1.91 times more open to accessing support. Location affects openness to change, with Ukraine-based individuals being less open. Lastly, 29.5% consider alternative stress-coping methods, with 40% open to future psychological help.

Our findings show differences in populational attitudes towards MH in Ukraine during the war and therefore the importance of any potential intervention to precisely tailor certain subgroups, beliefs behaviors and needs within them to have a higher chance of being accepted and increase MH support utilization in the population overall.

None Declared

The perception that individuals afflicted with mental disorders may exhibit potential harm or unpredictability is common in the general population and, as studies have shown, mental health-related stigma is not confined to the broader public but is progressively emerging as a concern within professional circles as well, adding additional burden to patients in psychiatric settings who already encounter an array of impediments stemming from societal prejudice.

In this cross-sectional study, we aimed to investigate the attitudes of adult and child psychiatrists towards people with mental health problems in Slovenia.

The stigmatizing attitudes were measured by an internet-based, anonymous survey using the Opening Minds Stigma Scale for Health Care Providers (total score and three subscales are the following: attitude, disclosure and help-seeking, social distance).

Altogether, n=90 practitioners (n=18 males, n=72 females) completed the survey. The bifactor ESEM model showed the best model fit (RMSEA=0.060, CFI=0.970, TLI=0.939); however, exploratory factor analysis results indicated the weakness of items 1 and 11. Those participants who have a possibility to attend case discussion groups are more willing to disclose their own mental health issues or seek help (8 (7-9) vs 9 (8-11.5)); however, they prefer more social distance from their patients (9(7.5-10) vs 7(6-9)). Gender differences were found as well, women seem to keep more social distance (p=0.031). Interestingly, those practitioners who reported spending 75% of their working hours with patients kept less social distance compared to those who engage in other activities (p=0.028).

This study is the first to describe the stigmatizing attitude of psychiatric practitioners in Slovenia from their perspective, and it provides directions for anti-stigma interventions.

None Declared

The negative impact of adverse childhood experiences (ACEs) on mental health has been well documented. While most of the evidence comes from samples of adolescents and young adults, few studies have investigated whether ACEs contribute to poorer mental health among older adults. In particular, depressive symptoms are common in old age, and they display heterogeneous patterns of development across individuals. Therefore, it is important to examine if ACEs are predictive of distinct trajectories of depressive symptoms among older adults.

Using longitudinal data from the English Longitudinal Study of Ageing (ELSA), we aimed to examine if ACEs could differentiate between distinct trajectories of depressive symptoms over eight years in community-dwelling older adults.

Participants from ELSA aged 60 or above who reported no psychiatric diagnoses and completed the items of ACEs at baseline (wave 3) were included in the current study. Nine items of ACEs were subject to a principal component analysis to identify the underlying subtypes. Data of depressive symptoms from waves 3 to 7 (2-year apart), assessed with the 8-item Centre for Epidemiological Studies Depression Scale, were extracted for modelling the distinct trajectories using latent class growth analysis. The trajectories were predicted by subtypes of ACEs using multinomial logistic regression, adjusting for childhood socioeconomic status, sex, age and ethnicity.

The final sample consisted of 4057 participants (54.4% female, mean age= 71.34 (SD= 8.14)). We identified five trajectories of depressive symptoms (Figure 1): ‘low stable’ (73.4%), ‘increasing then decreasing’ (9.9%), ‘high decreasing’ (7.1%), ‘high stable’ (5.7%) and ‘moderate increasing’ (4.0%). Four subtypes of ACEs (i.e., sexual abuse, separation from natural parents, family dysfunction and physical assault) were evident. Compared to the ‘low stable’ group, higher levels of family dysfunction were reported in the ‘increasing then decreasing’ (aOR = 1.35, 95% CI [1.10 - 1.66], p = .012), ‘high stable’ (aOR = 1.59, 95% CI [1.30 - 1.96], p < .001) and ‘moderate increasing’ (aOR = 1.55, 95% CI [1.18 - 2.04], p = .011) groups. The ‘high stable’ group also reported a higher level of separation from natural parents than the ‘low stable’ group (aOR = 1.34, 95% CI [1.04 - 1.72], p = .047). Sexual abuse and physical assault did not predict any group differences.

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Distinct trajectories of depressive symptoms among older adults were predicted by family dysfunction in childhood. Our findings suggested that the negative impact of ACEs on mental health may extend beyond adolescence and young adulthood into the old age.

None Declared

While transient loneliness refers to feelings that last for a short time (less than two years), chronic loneliness alludes to feelings that last more than two years. Transient loneliness can appear after stressful life events such as retirement and loss of close social connections whereas chronic loneliness is more strongly related to maladaptive social cognition, poor social support, and lack of intimate relationships. In comparison to transient loneliness, chronic loneliness is more strongly linked to mental health problems, particularly the incidence and recurrence of depression. Therefore, understanding the specific risk factors for both types of loneliness would be of great utility in mitigating their impact on mental health.

Our aim was to test distinct measures and risk factors for chronic and transient loneliness as well as cross-sectional and longitudinal associations of transient and chronic loneliness with depression.

Responses from participants in Wave 5 (T1, 2013) and Wave 6 (T2, 2015) of The Survey of Health, Ageing and Retirement in Europe (SHARE) (N=45,490) were analyzed. The existence of clinically significant symptoms of depression was defined as reporting a value≥4 on the Euro-D scale. Loneliness was measured through 3-item loneliness scale and a single question. Both measures were tested in separate logistic regression models to identify risk factors for transient (loneliness at T1 but not at T2) and chronic loneliness (loneliness at both time points) as well as their impact on depression.

Between 47% and 40% of the cases of loneliness became chronic, according to the UCLA scale and the single question, respectively. Risk factors for both loneliness courses were being female, not being married, having a low educational level, having a poor physical health, having a poor social network and living in a culturally individualistic country. Risk factor for chronic loneliness were stronger, particularly those related to health status and social networks. Chronic loneliness showed also a strong association with depression both cross-sectionally and longitudinally, while transient loneliness showed a weaker cross-sectional association and markedly lower probabilities in the longitudinal association.

Risk factors for chronic loneliness and measures of the temporal dimension of loneliness should be considered in psychosocial interventions designed to prevent mental disorders.

None Declared

In Ontario, Canada, patients may be admitted to the hospital involuntarily if they are deemed to be suffering from symptoms of a mental disorder that may result in imminent serious bodily harm to themselves or others, or that may cause serious physical impairment to themselves (e.g., inability to keep themselves safe and warm in the winter). This measure can be life-saving. However, in addition to ethical and human rights considerations, resorting to coercive admissions may be an indication that those who are suffering from mental illness are not able to access or receive timely and appropriate intervention. While recent studies have suggested that the rate of involuntary hospital admission may be increasing, data on social determinants of involuntary hospital admissions are limited.

We examined social factors associated with involuntary admissions using a Canadian provincial database.

Binary logistic regression models were conducted to examine the associations between social factors (low income, indigeneity, rurality, housing type) and involuntary admissions, controlling for age, sex, and psychiatric diagnoses. Data from March 2019 to March 2021 was extracted from the Ontario Mental Health Reporting System admission dataset, comprising of a sample of 9,848 patients admitted to eight psychiatric hospitals in Ontario. Odds ratios and 95% confidence intervals are reported.

In 2021, the proportion of involuntary patients increased significantly by 6.8 percentage points to 55.7% compared to the previous year (48.9%). Indigenous status (First Nations, Metis, Inuit) [1.75 (1.38-2.21) **], living in rural areas [2.78 (2.48-3.12)], living in assisted residence [1.41 (1.21-1.64) **], homelessness [1.63 (1.38-1.91) **], male sex [1.21 (1.10-1.33) **] and younger age [0.99 (0.98-0.99) **] were associated with involuntary admissions, while income was not a significant factor. Compared to a diagnosis of a psychotic disorder, substance use disorders [0.11 (0.10-0.13) **] and mood and anxiety disorders [0.32 (0.29-0.36) **] showed decreased odds of involuntary admission, while neurocognitive disorders increased the odds of involuntary admission [3.86 (2.91-5.11) **].

Consistent with other findings, involuntary psychiatric hospital admissions in ON, Canada, have increased recently, which may in part be related to the pandemic. Rurality, indigenous status, and unstable housing have been found to be associated with involuntary admissions. The study findings support the need for better preventive and intervention strategies to serve vulnerable psychiatric patients, including addressing the social determinants of health such as housing, and increasing access to culturally competent and safe community-based mental health supports and services.

None Declared

The study aims to explore the utility of BDNF Val66Met polymorphism as a potential biomarker in Indian bipolar disorder patients and its correlation with clinical characteristics.

Genotyping Val66Met in BDNF gene

Exploring its association with bipolar disorder (BD).

150 consenting BD patients and matched controls were recruited using a case-control study design. BD severity was assessed using Young’s mania rating scale and the Clinical Global Impression - Severity (CGI-S) scale. BDNF Val66Met polymorphism was identified through real-time PCR after DNA extraction. Data was tested for normal distribution. Genotype frequencies between two groups were compared and the Hardy-Weinberg equilibrium assumptions were tested using Chi-Square tests. Clinical-genotypic associations were explored using the Kruskal-Wallis test and confirmed using hierarchical regression.

Our sample had more males (60%) than females (40%) with mean age of 35.05 years. Most patients had established bipolar disorder and were severely ill (CGI: 38.75, YMRS). Val66Met SNP genotype frequency differed significantly between cases and controls. Val66Val genotype and Val allele were higher in cases. Results consistent with Hardy-Weinberg equilibrium.Table 1.

Genotype frequencies of BDNF (rs6265) in cases and controls

Our study found that Val66Val genotype and Val allele were higher in cases and could be a potential biomarker for bipolar disorder (BD), which is consistent with previous research conducted on the European population. However, further investigations are required to gain a more comprehensive understanding of its impact on BD, including its association with serum BDNF levels, treatment outcomes, and a more diverse study population.

None Declared

Pharmacogenomic testing in psychiatry is an emerging area with the potential clinical application of guiding medication choice and dosing. However, this has not been adopted widely due to a combination of barriers that include a varying evidence base, clinician and patient familiarity and acceptance, uncertainty about cost-effectiveness, and regulatory requirements.

This review aims to examine recent updates in this field and provide a contextualised summary and recommendations for Asian populations. The recommendations serve to guide healthcare professionals in the utility of pharmacogenomic testing in psychiatric practice.

A review of recent literature about current evidence and guidelines surrounding pharmacogenomics in psychiatric practice was carried out with particular attention paid to literature evaluating Asian populations. Literature was reviewed for the different classes of psychotropics with supplementary information about Asian populations included where available. Existing evidence about combinatorial pharmacogenomic panels was also reviewed.

In line with the available body of evidence, we recommend that pharmacogenomic testing should be employed as an augmenting tool to guide medication selection and dosing in certain clinical situations, and not as part of standard or routine clinical practice. Pharmacogenomic testing should also be mainly limited to the known drug-gene pairs such as the anti-depressants and CYP2C19 or CYP2D6. Clinicians should also be aware that many of the gene-drug associations have not been evaluated for clinical outcomes. Combinatorial pharmacogenomic panels are not presently recommended as there is limited and inconclusive available evidence on clinical outcomes.

Pharmacogenomic testing in psychiatry is not recommended as standard or routine clinical practice. Exceptions may include concerns about drug concentrations (due to metaboliser status) or potential severe adverse drug reactions/ Pharmacogenomic testing should be mainly limited to the known drug-gene pairs such as the anti-depressants and CYP2C19 or CYP2D6.

None Declared

Although suicide claims more lives than war and homicide, we still have no sufficient and effective methods either for its prediction or for its prevention. Our screening methods are laborous and subjective both on the side of the patient and on the side of the clinician. Understanding the genetic background of suicidal behaviour would help identify biomarkers for screening as well as pathways as potential targets for novel intervention and prevention approaches. However, in spite of a number of GWAS studies, results are few and rarely replicate, and generally accurate phenotyping and sufficient consideration of environmental stressors is also missing.

In our present study we performed a genome-wide analysis study for suicidal ideation in interaction with early childhood traumas in a deep-phenotyped general population sample.

Our analysis used data from 1800 volunteers in the NewMood project. As outcome phenotype the suicidal ideation item of the Brief Symptom Inventory was used. A modified version of the Childhood Trauma Questionnaire was used to assess early adverse experiences. A genome-wide association analysis was performed with Plink 1.9, including a total of 3,474,641 variants after quality control steps, followed by genome-wide by environment interaction analyses. Our models included control variables for sex, age, and the top 10 genomic principal components. Functional annotation of SNPs was carried out using FUMA v1.5.6, gene-based tests were performed using MAGMA v1.08.

7 SNPs met suggestive significance in main effect analyses, of which 2 reached genome-wide significance including rs79912020 (p=3.21E-10, β=0.746) and rs10236520 (p=1.71E-08, β=0.484), with no significant findings in gene-based tests. Interaction analyses with childhood adversities yielded 31 SNPs that met genome-wide significance, including rs7983955 (p=2.28E-11, β=0.182), rs141039461 (p=3.90E-11, β=0.0541), rs12692827 (p=3.69E-10, β=0.0612) as the top SNPs. In interaction with childhood adversities, 31 genes showed a significant association in gene-based tests, including RBFOX1 (p=1.09E-10), GRM7 (p=1.20E-10), MTCH1 (p=5.59E-09), and CDH13 (p=6.60E-09) as the most significant findings.

Our results indicate several important novel SNPs associated with suicidal ideation when considered in interaction with the effect of childhood adversities. Furthermore, gene-based analyses replicate several genes playing a key role in central nervous system function such as GRM7 (encoding metabotropic glutamate receptor 7) or previously implicated in association with suicide (CDH13) or suicide-related factors such as aggression (RBFOX1).

Funding: NAP2022-I-4/2022, K143391, 2019-2.1.7-ERA-NET-2020-00005, TKP2021-EGA-25

None Declared

Addressing mental and physical health problems and promoting wellbeing in educational settings is a global priority. Teachers present a high risk of stress and burnout, which negatively impacts their professional performance as well as their mental and physical health. Compassion-based interventions have been found effective in promoting psychosocial and physiological wellbeing.

The current paper presents preliminary findings of the impact of a 6-module Compassionate Mind Training intervention for Teachers (CMT-T) on immunological markers and the Conserved Transcriptional Response to Adversity (CTRA; a gene expression signature that involves a group of 53 genes: pro-inflammatory genes, type I interferon response and genes related to antibody synthesis).

A pilot non-controlled study was conducted in a sample of public-school teachers in Portugal (n=36). Participants were assessed at 4 time-points: 1) Extended Baseline Control_M0, in order to establish a within-subjects psychological and biophysiological baseline (8 weeks before the start of the CMT-T); 2) Pre-intervention_M1 (8-weeks after M0); 3) Post-intervention_M2 (8-weeks after M1); and 4) Follow-up_M3 (3 months after the CMT-T end). In all assessment moments, participants completed a set of psychological self-report measures and were assessed in immunological and epigenetic biological markers through the collection of blood. After M1, teachers completed the 8-week group CMT-T intervention and given access to its resources and materials. They were instructed to practice daily and incorporate the teachings in their personal and professional lives. All assessments and the CMT-T intervention took place at the schools.

Preliminary data on the impact of CMT-T on Immune Response Profiling revealed that teachers’ Natural Killer (i.e., NK) cells were decreased after the CMT-T intervention. In regard to the CTRA gene expression, results showed that type one interferon response genes (e.g., IFI16, IFI27L2, IFITM2, IFITM3, IFITM4P) were decreased after the intervention. In addition, we observed that the gene c-Jun, a pro-inflammatory gene, had a decreased expression after the CMT-T intervention.

These preliminary findings seem to corroborate previous studies involving the type one interferon response, the pro-inflammatory genes and antibody synthesis genes in a signature involving 53 genes previously described as the CTRA gene signature. Furthermore, our results suggest that cultivating compassion using a compassion focused intervention may have a positive impact on markers of the immune system response, associated with how our bodies respond to stress, infection and cancer, as well as, on reducing the expression of genes related to our bodies’ response to stress and inflammation.

None Declared

ASCL1 (Achaete-scute homolog 1) is a neuron-specific transcription factor involved in CNS maturation in the mammalian brain. It has been shown to be associated with schizophrenia (SZ), Parkinson’s disease, and the development of brain tumors. ASCL1 is expressed in the neuroblastoma cell line SH-SY5Y, which is a widely used model for the study of neurodevelopmental diseases, including SZ.

The aim of this work was to study the effect of functional ASCL1 knockout on the transcriptional landscape of SH-SY5Y cells in undifferentiated and neuron-like phenotypes.

For ASCL1 deletion, SH-SY5Y was sequentially transduced with two lentiviral vectors. One pLV-rtTA-Cas9-(nls)-pCMV-eGFP-PuroR-T2A-rTetR (derived from pCW-Cas9 and pEGFP-Puro) construct encoded Cas9. Stably transduced lines were selected for 3-5 days on puromycin (2 g/L). The inducibility of Cas9 expression was checked after adding the inducer oxytetracycline to the culture medium. The second construct (based on pLK05-tagRFP) encoded, a pair of guide RNAs targeting the start and end of the ASCL1 gene. The sgRNA construct was transduced into the SH-SY5Y-Cas9 cell line in parallel with a nontemplate control (NTC gRNA) as a negative control. Cas9 expression was induced with oxytetracycline for 2 days. Individual clones were obtained by serial dilutions. ASCL1 partial deletion in the clones was confirmed by PCR followed by Sanger sequencing. Disruption of ASCL1 protein synthesis was confirmed by western blot analysis. SH-SY5Y differentiation was induced by retinoic acid (RA). The transcriptomes of mutant clones and NTC controls before and after RA-induced differentiation were sequenced using Illumina technology.

RNAseq data show that a wide range of genes are differentially expressed between control NTC gRNA and wild-type SH-SY5Y. This can be explained by insertional mutagenesis of lentiviral vectors and/or cellular response to the presence of lentiviral constructs. Therefore, we compared the transcriptomes of the ASCL1-del line with NTC control. Differentially expressed genes (DEGs) are predominantly associated with the pathogenesis of SZ, bipolar and depressive disorders. DEGs in ASCL1-del are involved in cell mitosis, neuronal projection, neuropeptide signaling, and formation of intercellular contacts including the synapse. During RA-induced differentiation, ASCL1 activity is restricted to the regulation of a small subset of genes involved in neuroplasticity.

We have established a valid cellular model to study ASCL1-mediated mechanisms associated with SZ. ASCL1 dysfunction promotes SZ development predominantly before neuronal differentiation begins, slowing cell proliferation and preventing the formation of neuronal signatures.

None Declared