Previous studies have indicated a potential increase in risks of mental disorders among the offspring of mothers with depressive disorders. However, the association between maternal exposure at different developmental periods, including the period around pregnancy, and the offspring’s risk for adverse mental health outcomes remain unclear. Additionally, there is a lack of studies controlling for potential confounding by familial factors.

To determine the association between the timing of maternal depression around pregnancy and the risk of mental disorders among the offspring.

Population-based cohort study using linkage from Swedish national registers including 4,051,192 live singleton births in 1973-2010. Individuals were followed from age 3 until the first date of mental disorders diagnosis, emigration, death or 31 December 2013. We included the following diagnoses: depression, postpartum depression, neurotic disorders, stress-related disorders, alcohol use disorders, drug use disorders, attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), intellectual disability, behavioural disorders (child-/adolescent-onset), schizophrenia, other psychotic disorders, bipolar disorders, eating disorders, personality disorders, and others. Timing of maternal depression was defined as the earliest date of diagnosis or antidepressant dispensation around pregnancy, categorised into ‘1 year before conception’, ‘during pregnancy’, and ‘1 year after childbirth.’ Hazard ratios (HR) were estimated using Cox regression, adjusting for potential confounders. We also stratified the associations by age at follow up and birth year. To account for familial confounding, comparison was also made within full siblings.

In the population-based analysis, maternal depression was associated with a higher risk of overall mental disorder diagnosis in offspring in all three time periods, although the association tends to be stronger during the first year before conception (HR 1.90, 95% CI 1.78-2.03) and somewhat attenuated afterwards (HR during pregnancy 1.77, 95% CI 1.69-1.84; HR 1 year after childbirth 1.68, 95% CI 1.57-1.79; Figure 1). However, the associations were attenuated to null in the sibling analysis (HR overall mental disorders 1 year before conception 0.94, 95% CI 0.83-1.07; during pregnancy 1.08, 95% CI 0.98-1.17; 1 year after childbirth 1.00, 95% CI 0.88-1.13). Similar patterns were observed in most mental disorder diagnoses (Figure 1), across age at diagnosis (Figure 2), and birth year (Figure 3).

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While maternal depression before, during, and after pregnancy is predictive for the offspring’s mental health development, the link is likely driven by shared familial genetic and environmental factors.

None Declared

Evidence links early adolescent cannabis use (CU) to long-term health risks, but most studies lack comprehensive early-life confounder data and rely on subjective health measures.

To assess the association between adolescent CU trajectories and healthcare use for physical and mental health problems (P&MHP) in young adulthood.

Data from the Québec Longitudinal Study of Child Development, a 23-year population-based birth cohort (N = 1,591), were linked to healthcare administrative records (hospitalizations, outpatient, and ER visits). CU trajectories (exposure) were derived from age of onset and frequency data (ages 12-17) using group-based trajectory modeling. Missing data on pre-exposure confounders were multiply imputed. Overlap-weighted logistic regression was used to assess the adjusted associations between these trajectories and healthcare use for P&MHP between ages 18-23.

Three CU trajectories were identified: non-users, late users, and early users (Figure 1). Early users had a higher risk of healthcare use for any mental disorder (OR 1.55, 95% CI 1.17-2.06), common mental disorders (OR 1.69, 95% CI 1.19-2.39), substance-related disorders (OR 2.25, 95% 1.24-4.10), and hospitalizations for physical diseases (OR 1.57, 95% CI 1.03-2.38) compared to non-users. No significant differences were found between late and non-users.

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These findings highlight the need for targeted interventions during adolescence to mitigate long-term health risks. Prevention efforts should prioritize early users, and be focused on integrated social, mental, and physical care.

None Declared

Social isolation refers to the lack of objective social contact and is one of the health risk factors. Previous studies have shown that social isolation is associated with several physical and mental disorders. However, the relationship between social isolation and schizophrenia remains unclear.

This study aimed to investigate whether there is a potentially causal association between social isolation and schizophrenia.

The UK Biobank (UKB) is a large population-based cohort study. In this study, social isolation was assessed using self-reported questionnaires. Participants were categorized into socially isolated and non-isolated groups based on the scores. We identified cases of schizophrenia through hospitalization records and death registrations in the UKB. Propensity score matching was used to reduce the influence of confounding factors. We estimated the hazard ratios (HRs) of social isolation to schizophrenia using Cox regression. In addition, we estimated the causal association between social isolation and schizophrenia by two-sample Mendelian randomization analysis. Genetic data for social isolation and schizophrenia were extracted from the UKB and the Psychiatric Genomics Consortium, respectively.

315 cases of schizophrenia were documented during a mean follow-up of 12.3 years. After adjusting for demographic, socioeconomic, and lifestyle factors, the risk of schizophrenia in the socially isolated group was 1.73 times higher than that in the non-socially isolated group (95% CI, 1.37-2.18). Results from two-sample Mendelian randomization analysis showed that participating in more other group activities was associated with a reduced risk of schizophrenia (OR, 0.49; 95% CI, 0.31-0.77).

Social isolation was potentially causally associated with an increased risk of schizophrenia. The results of this study emphasize the importance of reducing the risk of developing schizophrenia through initiatives to reduce social isolation and increase social activities.

None Declared

Alcohol consumption, monitoring its prevalence and temporal trends, is one of the leading epidemiological interests in public health. When there are significant changes over time, understanding these new trends is crucial for health professionals. In the Czech Republic, a significant and sustained decline in alcohol use among the adolescent population has been observed since the mid-2010s (Kážmér & Orlíková Adiktologie. 2017; 17(2):118–132; Kážmér & Csémy J Public Health Res. 2019; 8(1):1493). The decline was in line with general trends across Europe and North America (Kraus et al. Addiction. 2018; 113(7):1317–1332). However, the factors driving the decline were attributed to new modes of adolescent leisure activities (Chomynová & Kážmér J Subst Use. 2019; 24(6):630–637) rather than changes in prevention-related issues (Pennay et al. Drug Alcohol Rev. 2018; 37(S1):S115–S119). If the decline among the adolescent population has continued into later age groups, there should also be a significant decline in today’s Czech young adults.

The study examines temporal trends in alcohol use in the general population of the Czech Republic, with an age-specific focus on young adults under 25 years of age.

Time series of nationally representative data on alcohol use were compiled from the National Survey on Tobacco and Alcohol Use in the Czech Republic. The large-sample representative survey, conducted annually by the National Institute of Public Health, provided high-quality data on alcohol use among the general Czech population aged ≥15 years in 9 cross-sectional time periods: 2012, 2014, 2016, 2018–2023. The subgroup of respondents aged 15–24 years was selected. Time trends for three main measures on alcohol use were considered: i) mean annual alcohol consumption (in litres per person per year); ii) prevalence of binge drinking (%); iii) prevalence of abstainers (%).

Among the Czech population aged 15–24, all the three measures on alcohol use have improved in recent time periods. In particular, the estimated mean annual alcohol consumption decreased significantly from 8.9 litres (95% CI: 6.5–11.2) of pure ethanol per person per year in 2012 to 5.1 litres (95% CI: 4.0–6.2) in 2023. The prevalence of last year abstainers increased accordingly: from 8.6% (95% CI: 5.4%–12.8%) in 2012 to 13.1% (95% CI: 8.6%–17.6%) in 2023. In a similar vein, there was also an improvement in the prevalence of binge drinking.

There was a noticeable decrease in alcohol use among the Czech young adults aged 15–24 years in recent periods, especially after 2020. Further research will be conducted to examine this trend in more detail.

The study was supported by the Operational Program Johannes Amos Comenius, project number CZ.02.01.01/00/22_008/0004583.

None Declared

There is a prevailing paradox in workplace mental health. Never has so much been spent on prevention, intervention, and regulatory programs yet the prevalence of employee mental ill-health has not only not improved, but rates are seemingly on the increase.

Two evaluate 2 explanations (a) has the reported prevalence of specific psychosocial workplace risk and protective factors changed over the last two decades (e.g., is work getting more stressful), and (b) are there trends, and generational differences, in the impact of these factors on worsening or buffering mental health (e.g., are employees becoming less resilient).

We use a 20 year population based cohort study (n=19,744).

(a) We estimated the linear trend over time (2001 to 2020), to determine the population-trends of reporting higher levels of job demands, control and complexity.

(b) To assess cohort differences in resilience to job stressors we estimated regression models predicting mental health (MHI-5 scores) by each psychosocial risk and birth cohort. Each model included the interaction between the self-reported psychosocial risk factor (independent variable) and birth-cohort (moderator variable) to estimate the dependency for each cohort. The marginal slope between the level of the risk factor and mental health for each cohort was estimated by the delta method (see below). Differences between the marginal slopes of adjacent cohorts were tested with adjustment for pairwise comparisons.

From 2000 to 2020 employees report trends of increased perceived job demands and decreasing autonomy in deciding how work was completed, but increasing control over when work is carried out and greater skill use(fig 1). High levels of demands have a stronger negative impact on the mental health of Millenailas than older cohorts at a similar age, and this younger cohort benefits less from the buffering effect of autonomy at work imporving mentla health (fig2).

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Over the last 20 years, employees report increasing job demands and decreasing freedom in deciding how work was completed, but increasing control over when work is carried out. Although this reflects, in part, an age effect as both demands and control peak in middle age, more recent cohorts also report higher demands and less control at any given age. In addition, the marginal negative impact of higher levels of job demands on mental health has increased in younger cohorts, alongside reducing psychological benefits from autonomy and control compared with older cohorts.

This combination of employees viewing work as becoming more stressful and younger employees increased sensitivity to work stress effects may explain part of the paradox and have major implications for employers, insurers, regualtors and benefit systems.

None Declared

The aim of this study was to investigate the associations between smartphone and social media use and mental health outcomes among adolescents in Ireland.

This study aimed to fill a gap in the existing literature by examining specific types of online activity, such as cyberbullying and “sexting” (sending sexually explicit messages), and the independent associations of these activities with worse mental health.

This study is a cross-sectional analysis of secondary data from the 2023 Planet Youth Partner survey. The study population was 4,544 mostly 15- and 16-year olds from Cavan, Monaghan and North County Dublin. The dependent variable was the total Strengths and Difficulties Questionnaire (SDQ) score, a tool commonly used to assess mental health status. Independent variables included hours of social media use, experiences of cyberbullying, body image perceptions, and involvement in sexting. Multivariable logistic regression models were employed to determine the associations between these variables and mental health outcomes, controlling for potential confounders such as gender, sleep duration, and maternal education level.

The study found significant associations between several online activities and worse mental health. High use of social media (4 hours per day or more) was associated with a 62% greater risk compared to those who used it for about 1 hour or less.

Cyberbullying was a also strong predictor of poor mental health, with victims nearly twice as likely to have a high SDQ score. Negative perceptions of one’s own body image and participating in sexting were also significantly associated with worse mental health outcomes.

Gender differences were observed, with females more likely to be victims of cyberbullying, to be asked for and to send sexually explicit messages, and to have worse mental health outcomes when compared to males. Insufficient sleep was also a significant predictor, with those sleeping for 6 hours or less per night having more than twice the risk compared to those who slept for the recommended 8 hours or more.

The findings of this study suggest that specific aspects of smartphone and social media use, particularly high usage and negative online experiences, are independently associated with poorer mental health outcomes in adolescents. These results are consistent with international evidence and highlight the need for targeted public health interventions to mitigate the risks associated with this technology. The study recommends developing evidence-based guidelines for parents and teachers to promote healthier online behaviours among adolescents in Ireland. It also calls for a national Public Health campaign and policy measures to enforce stricter regulations on social media companies and protect young people from harmful online experiences.

None Declared

While the immediate physical health consequences of hypertensive disorders during pregnancy are well-documented, their potential impact on children’s mental health and cognitive outcomes remains relatively under-investigated. Research exploring the link between hypertensive disorders during pregnancy and cognitive function has yielded conflicting findings. Some studies report associations, while others fail to establish a link or even suggest a protective effect. Many of these studies have focused on children with intrauterine growth restriction, low birth weight, small for gestational age, and/or preterm births—factors already known to influence cognitive development. Furthermore, almost all of this research focuses on early childhood, leaving a critical gap in our understanding of the long-term effects into adolescence, a period characterised by rapid cognitive development and academic achievement.

This study aimed to examine the associations between hypertensive disorders during pregnancy and intelligence quotient (IQ) in children at the ages of 8 and 16 years.

Our study sample comprised participants in the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort, an ongoing population-based longitudinal birth cohort in Bristol, Avon, United Kingdom. Children’s IQ was measured using the Wechsler Intelligence Scale for Children (WISC-III). This study included over 4900 and 3300 mother-child pairs at ages 8 and 16, respectively. Binary and multinomial logistic regression analyses were used to estimate odds ratios for the associations.

Hypertensive disorders of pregnancy (gestational hypertension and/or pre-eclampsia) were not found to be associated with lower IQ scores in children at ages 8 and 16. In the multinomial logistic model, we found children born to mothers with gestational hypertension but not pre-eclampsia were more likely to have above-average IQ at age 16 compared to average IQ children born to mothers without gestational hypertension (OR = 1.42; 95% CI: 1.03 – 1.94). This association did not persist when children with below-average IQ were used as the reference category in the analysis, and no such associations were also observed at the age of 8 years.

Our findings revealed no evidence of associations between hypertensive disorders during pregnancy and lower IQ scores in children ages 8 and 16. The observed association between gestational hypertension and higher odds of having an above-average IQ at age 16 needs further investigation. Our findings were based on a cohort study with a longer follow-up period, offering a higher level of evidence than previous studies. The consistency of our findings across different developmental stages strengthens the validity of our results and suggests that any potential effects of hypertensive disorders during pregnancy on cognitive function may be limited or transient.

None Declared

Mental disorders result from a complex interplay of genetic and environmental factors. However, the multiplicity of exposures and the complexity of mental health phenotypes pose a major challenge. The ‘exposome’ paradigm offers a holistic view of the environment that contrasts traditional hypothesis-driven approach in psychiatry. Within this framework, exposome-wide studies provide a novel tool to systematically identify phenotype-exposure relationships, offering an innovative perspective to map the exposome of mental health.

To map environmental factors associated with psychiatric diagnostic domains and symptom dimensions in the UK Biobank cohort. In this study, we aim to identify exposures unique to specific mental health outcomes, as well as those shared across conditions.

We analysed UK Biobank participants with complete Mental Health Questionnaire data (N = 157,298). Outcomes were classified as either psychiatric domains or symptom dimensions. After quality control, 294 environmental, lifestyle, behavioral, and economic variables were included. An Exposome-Wide Association Study (ExWAS) was conducted per outcome in two equally split datasets, applying Bonferroni correction for multiple testing (P < 1.70 x 10^-4). Missing exposure data was imputed using Multiple Imputation by Chained Equations. Variables associated with each outcome were then tested in a multivariable model.

In diagnostic domains, ExWAS analyses identified 26 to 165 significant factors. Multivariable analysis revealed 10 to 65 significant associations, with traumatic events, physical complaints, and sleep disturbances emerging across domains. Cannabis use was associated with common psychiatric disorders (ORs: 1.10-1.79), while computer use was uniquely linked to neurodevelopmental disorders (OR = 1.23). Eating disorders showed stronger correlations with food-related exposures. In symptom dimensions, ExWAS identified 46 to 180 significant factors. Multivariable analysis revealed similar exposure groups to those in diagnostic domains. Notably, self-harm was uniquely associated with childhood adoption (OR = 1.39).

This comprehensive mapping of exposome revealed that several factors, particularly in the domains of those previously well-studied were shared across mental health phenotypes, providing further support for transdiagnostic pathoetiology. Our findings also showed that distinct relations might exist. Continued exposome research through multimodal mechanistic studies guided by the transdiagnostic mental health framework is required to better inform public health policies.

None Declared

Depression and anxiety are global mental health concerns and contribute significantly to the global burden of human disease. Although psychotherapies and antidepressant drugs are effective and commonly used treatments for depression and anxiety, some patients do not achieve full remission of their symptoms and there remains a risk of residual symptoms.

To validate effect of supervised group exercise therapy in outpatient treatment of depressive and anxiety disorders.

A total of 126 individuals were screened for elevated depressive and anxiety symptoms. 86 participants aged between 18 and 65 years (Median=33 years; IQR 15; 62.8 % females) were randomly assigned to exercise group (EX, N=43) or relaxation group (REL, N=43). EX was planned to receive 36 sessions and REL 12 sessions during a 12-week intervention. Depressive symptoms were measured using Montgomery-Åsberg Depression Rating Scale (MADRS and MADRS-S) and anxiety symptoms using Becks Anxiety Inventory (BAI) at pre-, mid- and post-intervention.

The study is registered on ClinicalTrials.gov Register for RCT’s (NCT04714528).

Intention-to-treat analyses showed that both groups improved significantly in depressive and anxiety symptoms (MADRS: EX from 24.5±7.4 to 15.8±8.3 points, REL from 22.8±6.4 to 16.6±7.8 points. MADRS-S: EX from 27.6±7.2 to 19.6±8.1 points, REL from 26.3±7.1 to 18.7±9.5 points. BAI: EX from 25.0±12.2 to 16.4±9.9 points, REL from 24.3±12.4 to 17.0±12.6 points). However, there was no statistically significant difference between the groups in the degree of improvement. In addition, there was a high and differential attrition rate (51.2 % in EX vs 20.9 % in REL, p=0.007). It took longer than expected for the exercise group to finish the intervention (EX 19.2±5.1 weeks vs REL 14.8±4.0 weeks). Attrition analysis showed that individuals that had student as their main occupation were more likely to drop out and participants with sleep medication were more likely to adhere to interventions.

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The study reflects the challenges of outpatient, activity-based treatments for mild to moderate depressive and anxiety disorders regarding compliance, despite great efforts were made to keep the participants’ motivation throughout the study. Although both groups improved in depression and anxiety symptoms similarly, due to the lack of control group with no active treatment, it is difficult to assess possible placebo effect from this study. The differential bias from attrition and compliance makes it difficult to draw definitive conclusions.

None Declared

Depression is increasingly linked to immunological processes. Therefore, immune-based therapies, e.g., celecoxib, are being tested as augmenting treatment strategies. Many physiological processes during life are also linked to immunological changes. We tested the hypothesis that age affects treatment efficacy in a randomized controlled sample treated with the anti-inflammatory agent Celecoxib.

We test the combined role of age and an anti-inflammatory augmentation treatment for treatment response in depression. For a more in depth understanding we investigated the role of six methylation-based cell-types in these immunological processes in a second step.

113 individuals with a diagnosis of major depressive disorder were included in our analyses (Mage=44, 56% women, MMADRS= 27.7). All patients were treated with Vortioxetine and recruited stratified by high sensitive C-Reactive Protein (hsCRP; <= 3 vs. > 3 mg/L)> 3mg/L). Based on a randomized controlled design, augmentation with Celecoxib was administered to 55 patients. A second assessment was performed after 6 weeks of treatment (MMADRS 6W= 20.2). Cell type compositions of neutrophils, monocytes, B-cells, CD4+ and CD8+ Lymphocytes, and natural killer cells (NK), were estimated based on epigenome-wide DNA methylation markers (Illumina Infinium MethylationEPIC 850k BeadChip) using the Houseman method. Analyses were performed with linear regression models with MADRS6W as outcome. Our hypothesis was tested in the full sample. The additional analyses were performed stratified by age. All models were corrected for sex, hsCRP, and depression severity at baseline.

Our analysis showed a statistically significant interaction between age and treatment condition on depression outcome (p=0.040), with significant main effects for both variables in the model (intervention: p=0.045, age: p=0.022). Sex and hsCRP were no statistically significant contributors. The intersection was identified at 45.5 years. Younger individuals treated with celecoxib showed a more pronounced reduction in MADRS (Mreduction=-9.6), than older individuals treated with the same condition (Mreduction=-5.5). The stratified individuals younger than 45 years, showed that neutrophils were associated with better treatment outcome (p=0.028), whereas for individuals older than 45 years this was the case for B-cells and NK cells (p=0.011, and p<0.001, respectively).

Our results indicate that immunological profiles in depression and in relation to treatment may be age-dependent, which can have major consequences for treatment success with anti-inflammatory augmenting strategies. Replication in an independent sample is needed to confirm the role of age in immune-focused treatment strategies for depression.

None Declared

Anxious depression (AxD) as an independent diagnostic has been controversial, with many suggesting it as a transient state and others highlighting evidence of a worse outcome, severity, and increased suicide risk. The International Classification of Diseases (ICD-11) lists a related concept under 6A73, Mixed depressive and anxiety disorder. Previous literature on ketamine’s efficacy has mainly focused on either anxiety or depression, with limited comparison of both groups. Given their high comorbidity and shared pathophysiology, we aimed to assess ketamine’s efficacy in these populations.

This meta-analysis aimed to consolidate evidence from clinical trials evaluating ketamine therapy in AxD and Non-Anxious Depression (NAxD).

A search for published clinical trials in indexed journals and databases was conducted on August 11, 2024. Keywords included ketamine, anxiety, comorbidity, and depression, with no restrictions on language or publication date. Studies on bipolar or psychotic depression were excluded. A random-effects model accounted for variability, and subgroup analyses were performed.

Eight studies involving 536 participants (mean age = 39.0 years) were preselected. Seven studies defined “anxious depression” as a score of 7 or higher on the HAMD-AS, with AxD mean of 8.74 (±0.56) and NAxD mean of 5.83 (±1.9). MADRS scores were 35.18 (±2.22) for AxD and 31.97 (±2.29) for NAxD. The effect size of improvement in depressive symptom severity (as assessed by the MADRS) was not significantly different between the groups either 13 days after treatment (SMD = -0.07[-0.69, 0.55], p = 0.82, I2 = 73%) or 26-28 days after treatment (SMD = -0.30[-0.64, 0.04], p = 0.09, I2 = 21%). The overall depression response also did not significantly differ between the groups (odds ratio = 0.84 [0.50, 1.41], p = 0.52, I² = 13%). Insufficient data were available for remission rates.

Ketamine shows comparable efficacy in reducing depressive symptoms and achieving response in both groups. The group classified as AxD parallels previous reports of increased severity when reviewing baseline scores MADRS and other available scores. Thus, ketamine should be considered a viable treatment for patients with AxD, as they may have lower response rates to traditional antidepressants. This analysis was limited by the small number of studies, small sample sizes, and moderate heterogeneity. Differences in baseline depressive symptom severity and varying definitions of MDD with anxiety also constrained our analysis. Given the severity of symptoms in this population, we recommend developing better classification instruments for AxD. Further research is needed to explore remission differences in AxD and refine treatment strategies.

I. Borja De Oliveira: None Declared, A. Stephany: None Declared, M. Geremias: None Declared, D. Xavier: None Declared, F. Wagner: None Declared, A. Balduino de Souza: None Declared, M. O. Pozzolo Pedro: None Declared, D. Soler Lopes: None Declared, M. Carbajal Tamez: None Declared, J. Quevedo Shareolder of: Instituto de Neurociencias Dr. Joao Quevedo, Grant / Research support from: LivaNova; and receives copyrights from Artmed Editora, Artmed Panamericana, and Elsevier/Academic Press, Consultant of: EMS, Libbs, and Eurofarma, Speakers bureau of: Myriad Neuroscience and AbbVie., M. Teranishi: None Declared

Major depressive episodes (MDEs) occur in mood disorders such as major depressive disorder (MDD) and bipolar disorder (BD), affecting nearly one in four U.S. adults over their lifetime. The neurotrophic hypothesis suggests that disruptions in growth factor signaling contribute to MDEs. While brain-derived neurotrophic factor (BDNF) is well-studied, vascular endothelial growth factor (VEGF) may also play a crucial role, though evidence of its association with MDEs is inconsistent. Understanding VEGF is important for identifying predictors of treatment outcomes, such as those related to electroconvulsive therapy (ECT). This study explores the relationship between VEGF and MDEs, focusing on implications for ECT effects.

To consolidate evidence from studies evaluating the association between VEGF and ECT outcomes in patients experiencing an MDE.

A systematic search for published clinical trials and cohort studies was conducted on August 13, 2024, using keywords including ECT, VEGF, MDE, and mood disorders, with no language or publication date restrictions. We selected studies enrolling patients in a current MDE related to MDD or BD, excluding those focused on manic episodes. A fixed-effects or random-effects model was applied. Subgroup analyses were performed to investigate the data further.

Seven studies involving 621 participants (61.9% female; mean age: 50.2 years) were preselected. Six studies measured plasma VEGF levels; one assessed cerebrospinal fluid (CSF) levels. Plasma VEGF levels did not differ significantly between healthy controls and MDE patients, either before (SMD = 0.02 [−0.17; 0.21], p = 0.84, I² = 0%) or after ECT (SMD = 0.11 [−0.21; 0.44], p = 0.50, I² = 0%). Of the five studies reporting post-ECT VEGF levels, three found a significant increase from baseline. A significant correlation was observed between baseline plasma VEGF levels and depression response to ECT (r = 0.34, Z = 4.92, p < 0.0001, I² = 0%). Of the five studies examining increased VEGF levels after ECT and symptom reduction, only one found a significant association. A sensitivity analysis indicated substantial heterogeneity when including the CSF study.

Plasma VEGF levels were not significantly different in MDE patients compared to healthy controls, either before or after ECT. Baseline plasma VEGF levels positively correlated with ECT treatment response, suggesting they may provide neurotrophic support and predict outcomes. Despite robust findings and minimal heterogeneity, this analysis was limited by the low number of studies and small sample sizes. Further research is needed to explore the association between MDEs and VEGF, especially in the CSF, and to clarify the role of baseline VEGF in ECT treatment response.

I. Borja De Oliveira: None Declared, G. A. M. Alves: None Declared, D. Soler Lopes: None Declared, A. de Vasconcelos: None Declared, A. Stephany: None Declared, F. Reis Soares: None Declared, M. Kraide Piedade de Abreu: None Declared, M. Carbajal Tamez: None Declared, J. Quevedo Shareolder of: Instituto de Neurociencias Dr. Joao Quevedo, Grant / Research support from: LivaNova; and receives copyrights from Artmed Editora, Artmed Panamericana, and Elsevier/Academic Press, Consultant of: EMS, Libbs, and Eurofarma, Speakers bureau of: Myriad Neuroscience and AbbVie., M. Teranishi: None Declared

Major depression not only impairs individual health and labour market performance but also imposes significant economic burdens on society. It is linked to substantial costs through healthcare use, lost productivity and absenteeism. Recent genome-wide association studies have identified genetic markers associated with major depression, offering new insights into its genetic risk factors. However, the potential association of these genetic risks with educational attainment and career outcomes remains underexplored. Understanding this connection is crucial for addressing the broader public health and socio-economic implications of depression risk beyond clinical populations.

This study aims to investigate the relationship between genetic risk for depression and individual career performance in the general population of Finland from 1992 to 2017.

We utilised pooled data from the Finnish Finrisk (1992-2012) and FinHealth (2017) studies, which together include a population representative sample of individuals aged 25-64 (N=20,121). Genetic, survey and socio-economic registry data were integrated for this analysis. Using probit and semi-structural regression models, we examined various career performance indicators, with polygenic scores for depression (Howard et al. Nat Neurosci 2019; 22 343-352) as the main explanatory variable. Socio-demographic characteristics and genetic principal components were included as controls.

Our study revealed a negative association between higher genetic risk for depression and the likelihood of attaining higher education—an essential predictor of career success. Additionally, our study provides novel insights into how elevated polygenic risk for depression was linked to employment and self-employment rates, both directly and via educational pathways.

These findings highlight that genetic predispositions for depression can adversely affect career prospects in the general population, suggesting that the economic burden of depression extends beyond those clinically diagnosed. As effect sizes are modest, our results imply that supportive measures and compensatory behaviours could mitigate some of the educational and career disadvantages associated with higher genetic risk for depression.

A. Hazak: None Declared, J. Liuhanen: None Declared, K. Kantojärvi: None Declared, S. Sulkava: None Declared, T. Jääskeläinen: None Declared, V. Salomaa: None Declared, S. Koskinen: None Declared, M. Perola: None Declared, T. Paunio Consultant of: Idorsia Pharmaceuticals and Biogen (unrelated to the present work)

Major depressive disorder (MDD) is one of the most prevalent and disabling mental health conditions globally. Approximately one-third to half of MDD patients, suffer from difficult-to-treat depression (DTD), a condition marked by persistent symptoms that do not respond to multiple standard treatments. DTD is often associated with comorbid physical and psychiatric conditions leading to chronic disability and a reduced quality of life. The complexity of DTD poses a considerable challenge in clinical practice, underscoring the need for innovative treatment options.

Despite the demonstrated efficacy of esketamine in controlled clinical trials, real-world evidence is limited. This study aimed to address this gap by assessing the effectiveness of esketamine in routine clinical practice in DTD patients.

This prospective, naturalistic, open-label, observational study was conducted at Marqués de Valdecilla University Hospital in Cantabria, Spain. It included 33 patients diagnosed with DTD, comprising both unipolar and bipolar depression, as well as persistent depressive disorder (see table 1). Esketamine was administered intranasally in doses ranging from 56 mg to 84 mg, across three phases: induction, consolidation, and maintenance. Treatment effectiveness was measured using the MADRS, Clinical Anxiety Scale (CAS), and Clinical Global Impression (CGI). Functionality and quality of life were assessed with the Brief Functioning Scale (FAST) and the EQoL-5D (ESH). Assessments were conducted at baseline, 1-month, and 3-month. Data analysis was performed using SPSS v26, with repeated measures ANOVA and Pearson’s χ² tests employed to evaluate changes over time.

The final analysis included 33 patients with DTD and long-lasting current MDD episodes (table 2). Baseline MADRS scores indicated severe depression (39.12 ± 6). Significant reductions in MADRS scores were observed at both one month (21.61 ± 11.15) and 3-month (19.70 ± 11.65) compared to baseline. At 3-month, 54.5% of patients achieved a ≥50% reduction in MADRS scores, and 30.3% reached remission (MADRS < 12). Similar improvements were seen in anxiety (CAS) and health status (ESH) scores, with significant reductions noted over time. However, functional improvements (FAST) were not statistically significant (see table 3).

Esketamine demonstrated substantial effectiveness in reducing both depressive and anxiety symptoms in DTD patients over three months. More than half of the patients achieved a significant reduction in depression severity, with nearly a third reaching remission. The presence of late responders suggests that esketamine may benefit those initially unresponsive to treatment. These findings support esketamine as a valuable therapeutic option for DTD in real-world clinical settings.

None Declared

Evidence regarding metabolic alterations associated with maternal antenatal depression (AD) is limited, and their role as potential biomarkers improving the prediction of AD and adverse child birth, neurodevelopmental, and mental health outcomes remains unexplored.

To identify metabolic measures associated with AD.

To test whether the metabolic measures associated with AD increased the amount of variance explained in AD over its risk factors.

To test whether the identified metabolic measures increased the amount of variance explained in child gestational age and weight at birth, developmental milestones at ages 2.3-5.7 years and any mental or behavioral disorder by the ages of 13.1-16.8 years over AD, sex, and age.

To replicate the findings in an independent cohort.

In a cohort of 331 mother-child dyads, we applied elastic net regression to study associations between AD (history of medical register diagnoses and/or Center of Epidemiological Studies Depression Scale score during pregnancy≥20) and 95 metabolic measures analyzed three times during pregnancy. Child birth and mental health outcomes were extracted from national registers and child neurodevelopmental outcomes were mother-reported.

Elastic net regression identified 15 metabolic measures that collectively explained 25% (p<0.0001) of variance in AD, including amino and fatty acids, glucose, inflammation, and lipids. These metabolic measures increased the variance explained in AD over its risk factors (32.3%,p<0.0001 vs. 12.6%,p=0.004), and in child gestational age (9.0%,p<0.0001 vs. 0.7%, p=0.34), birth weight(9.0%,p=0.03 vs. 0.7%, p=0.33), developmental milestones at the age of 2.3-5.7 years(21.0%,p=0.002 vs. 11.6%,p<0.001) and any mental or behavioral disorder by the age of 13.1-16.8 years(25.2%,p=0.03 vs. 5.0%,p=0.11) over AD, child sex and age. These findings replicated in the independent cohort.

AD is associated with alterations in 15 metabolic measures, which collectively improve the prediction of AD over its risk factors, and birth, neurodevelopmental and mental health outcomes of the child over AD. These metabolic measures may become biomarkers identifying at-risk mothers and children for personalized interventions.

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Cognitive dysfunction has been identified as a key mediator of functional impairment in major depression and a contributing factor to antidepressant resistance. Theta burst stimulation (TBS) is a novel form of transcranial magnetic stimulation (TMS) that has shown greater efficacy and efficiency than conventional TMS in the treatment of treatment-resistant depression (TRD). However, its effects on cognitive symptoms in depression remain largely unstudied.

The objective of this study is to evaluate the impact of TBS on neurocognition in unipolar and bipolar TRD patients treated at a public hospital. Additionally, clinical, demographic, and treatment predictors of cognitive change were explored.

This is a follow-up study of n=64 patients with TRD (unipolar=48, bipolar=16) who received daily adjunctive TBS for 6 weeks. Cognitive performance was assessed before and after TBS using different versions of the Screening for Cognitive Impairment (SCIP-S), which measures immediate verbal learning, working memory, verbal fluency, delayed verbal learning, and processing speed. Cognitive performance in each domain was compared using paired t-tests. Global cognitive change was assessed by quantifying pathological domains at baseline and at the end of TBS. Differences in neurocognition between clinical responders (50% reduction on the HDRS) and non-responders to TBS were compared using ANOVA models. Additionally, possible predictors of cognitive change in each domain were explored using correlation analyses and multiple linear regressions, which included factors such as age, diagnosis, number of TBS sessions, treatment type, TBS modality (left unilateral vs. bilateral), clinical response, and baseline severity.

Patients treated with TBS achieved significant clinical response (68%) and cognitive improvement in the domains of immediate verbal learning, working memory, verbal fluency, and processing speed (mean differences of 2.16, 2.31, 1.30, and 1.05, respectively). Neurocognitive improvement was independent of clinical response. The percentage of improvement on the HDRS was only associated with improvement in the verbal fluency domain (p = .007). Left unilateral TBS and bipolar diagnosis predicted better global cognitive improvement in SCIP in regression models (p = .042, p = .037, respectively).

The results support the utility of TBS in treating cognitive dysfunction associated with TRD. Further larger studies are needed to clarify clinical and treatment predictors of cognitive improvement.

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Schizophrenia, affecting about 1% of the global population, is marked by positive, negative, and cognitive symptoms, leading to significant disability and a shortened lifespan due to physical health issues. Early intervention is crucial, as untreated psychosis can persist. This study examines changes in mRNA expression in the NRG-1/PI3K-AKT and DRD2 pathways in treated and untreated patients, hypothesizing that expression decreases and varies with treatment.

We aim to assess the impact of antipsychotic treatment on the expression levels of the PI3K/AKT/m-TOR signaling pathway, linked to the neurodevelopmental hypothesis of schizophrenia, and associated with the dopaminergic DRD-2 and glutamatergic NRG-1 systems. This study will examine mRNA expression of DRD-2, NRG-1, and PI3K/AKT/m-TOR in leukocytes from female schizophrenia patients before and after treatment. The findings may enhance our understanding of schizophrenia’s pathogenesis, identify potential genetic markers, and clarify the molecular effects of antipsychotic drugs.

Our study includes 25 healthy female volunteers and 25 female schizophrenia inpatients from Bakırkoy Prof. Dr. Mazhar Osman Mental Health and Neurological Diseases Training and Research Hospital. These inpatients met the experiment criteria, had not received treatment in the last 3 months, and were diagnosed with schizophrenia spectrum disorder according to DSM V criteria. After obtaining written consent, a sociodemographic form was completed. The Positive and Negative Symptom Scale (PANSS) was administered to eligible patients. Blood samples for DRD-2, NRG-1, and PI3K/AKT-1/mTOR mRNA expression analysis were collected from patients with PANSS scores of 95 or above before treatment and after scores decreased to 58 or below. Expression levels were determined by RT-PCR.

In untreated schizophrenia patients, NRG-1 mRNA expression was significantly lower, while PI3K and mTOR mRNA expressions were significantly higher compared to the healthy control group, with no change in AKT-1 mRNA expression as shown in Table 1. Compared to healthy controls, treated patients showed increased NRG-1 mRNA, unchanged PI3K and AKT-1 mRNA, and decreased mTOR mRNA as shown in Table 2. In treated patients, NRG-1 mRNA expression was significantly higher, and PI3K and mTOR mRNA expressions were significantly lower compared to untreated patients, with no change in AKT-1 as shown in Table 3. DRD-2 mRNA expression was undetectable in all groups.

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NRG-1, PI3K, and mTOR may contribute to schizophrenia pathogenesis, with NRG-1 and mTOR serving as potential genetic biomarkers. Antipsychotics affect molecular pathways, but not AKT-1, and DRD-2 is not expressed in immune cells.

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Schizophrenia is a chronic mental disorder marked by positive symptoms such as hallucinations and delusions, and negative symptoms such as social withdrawal and apathy. While traditional pharmacological treatments effectively manage positive symptoms, they often fall short in addressing negative symptoms and social functioning. Yoga has emerged as a complementary therapy that may help improve both. However, its overall impact remains uncertain.

This review aims to synthesize evidence on yoga’s effectiveness in reducing positive and negative symptoms of schizophrenia and enhancing social functioning.

A systematic search was conducted in Scopus, Web of Science, and PsycINFO in September 2024, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Included studies were peer-reviewed randomized controlled trials (RCTs) assessing yoga’s effects on symptom severity and social functioning in schizophrenia. A fixed-effects or random-effects model was applied, with subgroup analyses performed. Standard mean differences (SMDs) and mean differences (MDs) were used for effect size estimation.

Sixteen RCTs were included, involving 862 participants. Yoga (n = 393) was compared to three control groups: treatment-as-usual (n = 152), other physical activities (n = 124), and waitlist (n = 193). Yoga significantly reduced overall symptom severity relative to control, as shown by a decrease in PANSS scores (MD = -6.61, 95% CI -13.21 to -0.0, p = 0.05, I² = 82%). It significantly improved positive symptoms relative to waitlist (SMD = -0.87 [-1.70, -0.03]) and treatment-as-usual (SMD = -0.65 [-1.21, -0.09]), with effects comparable to those observed with physical activity (MD = -1.30 [-3.09, 0.49]). There were no significant effects on negative symptoms, with SMDs of -1.59 [-4.18, 1.01] for the waitlist and -1.16 [-2.41, 0.09] for treatment-as-usual, and a MD of -1.32 [-3.60, 0.97] when compared to physical activity outcomes. Additionally, yoga did not significantly impact social functioning, showing SMDs of -0.44 [-1.56, 0.68] for the waitlist and -0.44 [-2.29, 1.41] for treatment-as-usual, and a MD of 2.30 [-0.74, 5.34] for physical activity.

This review shows that yoga is effective in reducing overall symptom severity compared to controls and improves positive symptoms relative to treatment-as-usual or waitlist, but not compared to physical activity. There were no significant differences in alleviating negative symptoms or enhancing social functioning. These findings suggest yoga may be a promising adjunctive treatment for positive symptoms of schizophrenia, especially when traditional treatments are insufficient. Further high-quality RCTs with standardized protocols are needed to confirm these results and establish optimal treatment parameters.

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Functional outcome is a central clinical concern in inpatient psychiatry. Neurocognition is known to be an important factor in achieving a good functional outcome.

We have previously investigated whether cognitive dysfunction improves over the course of inpatient treatment, where acutely admitted patients are offered a combination of pharmacological treatment and cognitive remediation (Maihofer et al. J Clin Med 2024, 13, 4843). We now investigate the extent to which the functional outcome of patients with psychotic and affective disorders is associated with cognitive function over time.

Adult inpatients aged 18-66 years (female = 57.9%, male = 42.1%) were assessed with the Screen for Cognitive Impairment in Psychiatry (German version, SCIP-G: Sachs et al. Schiz Res Cogn 2021, 25, 100197; Sachs et al. Schiz Res Cogn 2022, 29, 100259). According to ICD-10 research criteria, 83 patients received an F2 diagnosis (schizophrenia, schizoaffective and delusional disorders), 61 patients met the criteria for bipolar disorder or mania (F30/F31) and 90 for 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).

SCIP scores at baseline correlate significantly with SCIP scores at time point two (r=.74, p<.001). The SCIP at baseline is significantly correlated with patients’ functional level (r=.32, p=.01). The higher the baseline SCIP score, the higher the GAF score (r=.33, p=.01). The higher the GAF score at baseline, the higher the SCIP score at time 2 (r=.26, p=.039). The higher the SCIP score at time 2, the higher the GAF score at time 2 (r=.42, p<.001).

During their stay in hospital, acutely admitted patients improved in function and neurocognition, regardless of their diagnostic classification. Functionality as measured by the GAF correlates significantly with cognitive ability as assessed by the SCIP-G.

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Due to the potentially severe side effects of antipsychotics, overtreatment is an important concern. Previous research focussed on antipsychotic polypharmacy and excessively high doses.

In this study, the aim is to map trends in potential overtreatment, antipsychotic polypharmacy, total antipsychotic dose and the subjective side effect burden. Moreover, the association of the total antipsychotic dose and antipsychotic polypharmacy with the subjective side effect burden will be investigated.

Data from a large (n>5000) naturalistic longitudinal cohort was used (PHAMOUS, 2013-2021). Potential overtreatment was defined as a total antipsychotic dose equivalent to >5mg risperidone, in combination with a high subjective side effect burden. Mixed effect models were used to investigate trends in potential overtreatment, antipsychotic polypharmacy, total antipsychotic dose and the subjective side effect burden. A mixed effect model was used to assess the association of total antipsychotic dose and antipsychotic polypharmacy with total subjective side effect burden.

Overall, 15,717 observations nested in 5,107 patients were used. About one-third of patients were potentially overtreated, with no change over time. The prevalence of a dose above the equivalent of 5 mg risperidone decreased over time, while antipsychotic polypharmacy prevalence increased. The total subjective side effect burden slightly decreased. A higher dose and antipsychotic polypharmacy was associated with a higher subjective side effect burden.

The subjective side effect burden did decrease the last decade. This might be caused by lower doses and more adequate use of polypharmacy. Still, the overtreatment rate is about one-third and the subjective side effect burden is still high. To reduce the subjective side effect burden and overtreatment, addressing inappropriate antipsychotic polypharmacy remains prudent.

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