The Clinical High Risk (CHR) group for transition to psychotic disorders (PD) is usually defined by the severity of positive symptoms, help-seeking and impairment in level of functioning. However, the CHR concept has a limited transition risk to PD. Recent studies have shown that some of the risks might be attributable to other symptoms.

This study investigates the association between affective and negative symptoms and the risk of transition to PD in a community-based population of 2185 participants in Turkey.

At baseline, psychotic and affective symptomatology were assessed. The same participants were contacted again 6-years later. The initial analysis aimed to assess the link between affective and negative symptoms, and the progression to PD. The independent variable, baseline symptomatology, was categorized into five groups: no Psychotic Experiences (PE)(reference), subclinical PE, subclinical PE accompanied by affective/negative symptoms, clinical PE, and clinical PE with affective/negative symptoms. In the subsequent analysis, the association between affective and negative symptoms at baseline and the onset of PE and PD at follow-up was evaluated. For this analysis, the baseline symptomatology was restructured into two categories: neither PE nor affective/negative symptoms (reference), and the presence of affective/negative symptoms without PE.

The findings from the initial analysis indicated that being part of the ‘subclinical PE only’ group at baseline was not associated with an increased risk of developing PD at follow-up. Being part of the ‘subclinical PE+affective/negative symptoms’ group was not significantly associated with PD at follow-up, although a trend was observed (OR: 3.22; z=1.90; p=0.057). Moreover, being classified as having ‘clinical PE only’ (OR: 6.23; z=2.57; p=0.010) and ‘clinical PE+affective/negative symptoms’ (OR: 8.48; z=4.17; p=0.001) at baseline was associated with an increased risk of developing PD at follow-up. Results from the subsequent analysis showed that being in the ‘affective/negative symptoms’ group at baseline was associated with an increased risk of new subclinical PE (RR: 1.98; z=3.20; p=0.001), new clinical PE (RR: 3.14; z=4.84; p=0.001), and new PD (RR: 4.21; z=2.17; p=0.030) at follow-up, compared to the ‘neither PE nor affective/negative symptoms’ group.

The results confirm that baseline severity of positive symptoms is significant in predicting transition to PD. In addition, the findings imply that not only positive symptoms but also affective and negative symptoms might contribute to the risk of transition to PD as well as incident psychotic symptoms. Defining CHR groups based on a combination of positive, affective and negative symptoms instead of focusing only on positive symptoms likely will help more accurately predict the transition to psychosis.

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Posttraumatic stress disorder (PTSD) and borderline personality disorder (BPD) often co-occur. There is growing motivation among clinicians to offer trauma-focused treatments, such as Eye Movement Desensitization and Reprocessing (EMDR), to patients with PTSD and comorbid BPD. However, a large subgroup of these patients does not sufficiently respond to trauma-focused treatment and is more likely to be excluded or dropout from treatment. Dialectical Behaviour Therapy (DBT) for BPD is well established and although there is some evidence that DBT combined with prolonged exposure is twice as effective in reducing PTSD symptoms than DBT alone, the comparative efficacy of trauma-focused treatment with and without concurrent PD treatment has not been investigated yet.

The current study will therefore evaluate the comparative clinical efficacy of EMDR with and without concurrent DBT in patients with PTSD and comorbid BPD.

Adult patients were randomly assigned to EMDR with (n = 63) or without concurrent DBT (n = 63). A wide range of clinician-administered and self-report assessments were conducted before, during and up to six months after treatment. The longitudinal change in PTSD severity as the primary outcome was measured using multilevel mixed regression in SPSS. The present study is part of the overarching Prediction and Outcome Study in comorbid PTSD and Personality Disorders (PROSPER), which consists of a second RCT comparing trauma-focused treatment with and without concurrent PD treatment in patients with PTSD and cluster C PD.

Results, available in January 2024, will reveal which treatment works best for this difficult-to-treat group of patients.

This is the first study to compare the clinical efficacy of EMDR with and without concurrent DBT in patients with PTSD and comorbid BPD. Results will reveal which treatment works best for this difficult-to-treat group of patients.

None Declared

We examined whether cannabis use contributes to the increased risk of psychotic disorder for non-western minorities in Europe.

We used data from the EU-GEI study (collected at sites in Spain, Italy, France, the United Kingdom, and the Netherlands) on 825 first-episode patients and 1026 controls. We estimated the odds ratio (OR) of psychotic disorder for several groups of migrants compared with the local reference population, without and with adjustment for measures of cannabis use.

The OR of psychotic disorder for non-western minorities, adjusted for age, sex, and recruitment area, was 1.80 (95% CI 1.39–2.33). Further adjustment of this OR for frequency of cannabis use had a minimal effect: OR = 1.81 (95% CI 1.38–2.37). The same applied to adjustment for frequency of use of high-potency cannabis. Likewise, adjustments of ORs for most sub-groups of non-western countries had a minimal effect. There were two exceptions. For the Black Caribbean group in London, after adjustment for frequency of use of high-potency cannabis the OR decreased from 2.45 (95% CI 1.25–4.79) to 1.61 (95% CI 0.74–3.51). Similarly, the OR for Surinamese and Dutch Antillean individuals in Amsterdam decreased after adjustment for daily use: from 2.57 (95% CI 1.07–6.15) to 1.67 (95% CI 0.62–4.53).

The contribution of cannabis use to the excess risk of psychotic disorder for non-western minorities was small. However, some evidence of an effect was found for people of Black Caribbean heritage in London and for those of Surinamese and Dutch Antillean heritage in Amsterdam.

Pre-diagnostic stages of psychotic illnesses, including ‘clinical high risk’ (CHR), are marked by sleep disturbances. These sleep disturbances appear to represent a key aspect in the etiology and maintenance of psychotic disorders. We aimed to examine the relationship between self-reported sleep dysfunction and attenuated psychotic symptoms (APS) on a day-to-day basis.

Seventy-six CHR young people completed the Experience Sampling Methodology (ESM) component of the European Union Gene-Environment Interaction Study, collected through PsyMate® devices, prompting sleep and symptom questionnaires 10 times daily for 6 days. Bayesian multilevel mixed linear regression analyses were performed on time-variant ESM data using the brms package in R. We investigated the day-to-day associations between sleep and psychotic experiences bidirectionally on an item level. Sleep items included sleep onset latency, fragmentation, and quality. Psychosis items assessed a range of perceptual, cognitive, and bizarre thought content common in the CHR population.

Two of the seven psychosis variables were unidirectionally predicted by previous night's number of awakenings: every unit increase in number of nightly awakenings predicted a 0.27 and 0.28 unit increase in feeling unreal or paranoid the next day, respectively. No other sleep variables credibly predicted next-day psychotic symptoms or vice-versa.

In this study, the relationship between sleep disturbance and APS appears specific to the item in question. However, some APS, including perceptual disturbances, had low levels of endorsement amongst this sample. Nonetheless, these results provide evidence for a unidirectional relationship between sleep and some APS in this population.

To assess cost-effectiveness of late time-window endovascular treatment (EVT) in a clinical trial setting and a “real-world” setting.

Data are from the randomized ESCAPE trial and a prospective cohort study (ESCAPE-LATE). Anterior circulation large vessel occlusion patients presenting > 6 hours from last-known-well were included, whereby collateral status was an inclusion criterion for ESCAPE but not ESCAPE-LATE. A Markov state transition model was built to estimate lifetime costs and quality-adjusted life-years (QALYs) for EVT in addition to best medical care vs. best medical care only in a clinical trial setting (comparing ESCAPE-EVT to ESCAPE control arm patients) and a “real-world” setting (comparing ESCAPE-LATE to ESCAPE control arm patients). We performed an unadjusted analysis, using 90-day modified Rankin Scale(mRS) scores as model input and analysis adjusted for baseline factors. Acceptability of EVT was calculated using upper/lower willingness-to-pay thresholds of 100,000 USD/50,000 USD/QALY.

Two-hundred and forty-nine patients were included (ESCAPE-LATE:n = 200, ESCAPE EVT-arm:n = 29, ESCAPE control-arm:n = 20). Late EVT in addition to best medical care was cost effective in the unadjusted analysis both in the clinical trial and real-world setting, with acceptability 96.6%–99.0%. After adjusting for differences in baseline variables between the groups, late EVT was marginally cost effective in the clinical trial setting (acceptability:49.9%–61.6%), but not the “real-world” setting (acceptability:32.9%–42.6%).

EVT for LVO-patients presenting beyond 6 hours was cost effective in the clinical trial setting and “real-world” setting, although this was largely related to baseline patient differences favoring the “real-world” EVT group. After adjusting for these, EVT benefit was reduced in the trial setting, and absent in the real-world setting.

Apathy is the most common neuropsychiatric symptom in Alzheimer’s disease (AD), however there are no approved treatments. In the recent Apathy in Dementia Methylphenidate Trial 2 (ADMET 2), methylphenidate treatment resulted in a significant reduction in apathy with a small to medium effect size. We assessed response in ADMET 2 to identify individuals likely to benefit from methylphenidate.

In ADMET 2, AD patients with clinically significant apathy were randomized to methylphenidate or placebo. Twenty-three potential predictors of treatment outcome chosen a priori for evaluation were divided into levels (e.g. anxiety present/absent). For each predictor, change in Neuropsychiatric Inventory apathy (NPI-A) due to methylphenidate for each level was estimated. Predictors with larger differences in effect (>= 2pt NPI-A) between levels were selected. Participants were then grouped into 10 subgroups by their index scores, constructed based on model-based prediction of response (NPI-A >=4).

In total 177 participants (66% male, mean (SD) age 75.7 (8.0), Mini-Mental State Examination 18.9 (4.8)) had 3 month follow-up data. Six potential predictors met criteria for multivariate modelling. The median Index score was -1.33 (range: -8.35 to 6.83). Methylphenidate was more efficacious in participants with no NPI anxiety (change in NPI-A - 2.21, Standard Error (SE):0.60, p=0.0004) or agitation (-2.63, SE: 0.68, p=0.0002), and who were on cholinesterase inhibitors (ChEI) (-2.44, SE:0.62, p=0.0001), between 52-72 years of age (- 2.93, SE:1.05, p=0.007), had normal diastolic blood pressure (-2.43, SE: 1.03, p=0.02), and more functional impairment (-2.56, SE: 1.16, p=0.03) as measured by the Alzheimer’s Disease Cooperative Study Activities of Daily Living scale. After 3 months of methylphenidate, 79% of participants with a higher index score (>median) responded (>= 4pt NPI-A) and 49% of those with a lower index score responded.

Individuals who were less anxious or agitated, younger, on a ChEI, had normal diastolic blood pressure, and with more impaired function were more likely to benefit from methylphenidate when compared to placebo. Consistent with its potential activating effects, methylphenidate may be particularly beneficial for apathetic AD participants with lower baseline anxiety and agitation.

Treatments trials for apathy in Alzheimer’s disease assess change scores on widely used assessment scales. Here, we aimed to determine whether such change scores on the Neuropsychiatric Inventory - Apathy (NPI-A) scale indicate clinically meaningful change.

Participants completing the Apathy in Dementia Methylphenidate Trial 2 (ADMET 2) were included. Participants in this randomized trial received methylphenidate or placebo for 6- months along with a psychosocial intervention. Assessments included Clinical Global Impression of Change in apathy (CGIC-A) and the NPI-A. Participants in both groups with complete data at the six-month visit were included. CGIC-A was assessed as improved (minimal, moderate or marked), no change, or worsened (minimal, moderate or marked). For CGIC-A levels, mean and standard deviation (SD) of the change in NPI-A from baseline was calculated. Spearman correlation determined the association between change in NPI-A and CGIC-A, and Mann-Whitney U tests determined differences between the ‘no change’ group and the ‘improved’ and ‘worsened’ groups. Effect size (mean NPI-A difference between either ‘improved’ and ‘no change’/ SD of overall change) were calculated. Differences were also assessed at 3 months as a sensitivity analysis.

Overall, 177 participants were included (median age: 77years, Mini Mental State Examination score: 19.3 (4.8), baseline NPI-A [mean, SD]: 7.9, 2.3), change in NPI-A: -3.7 (3.9). On the CGIC-A, 69 were improved, 82 showed no change, and 26 worsened. The Spearman correlation between NPI-A change and CGIC-A was 0.41 (p= 1x 10-8). The change in NPI-A among participants who improved was -5.3 (4.1) [W=1873, p= 3x10-4], among those who worsened was -1.2 (3.1) (W= 1426.5, p= 0.009) compared to those with no change (-3.2 [3.4]),. The NPI-A score for minimal clinical improvement was -4.5 (4.6) with a small effect size of -0.32, which was consistent at 3-months (-0.31).

A minimal clinically significant improvement over 3 and 6-months corresponded to a mean decline of 4.5 points on the NPI-A; however, there is considerable overlap in the NPI-A between levels of clinical impression of change.

Work stress, anxiety and depression have an enormous impact on the well-being of employees, their employers, and society. Due to the loss of productivity, common mental disorders have a substantial economic impact. Major depression alone has been attributed to 50% of long-term absences from work, and depressive symptoms are related to lowered productivity while at work. Anxiety also contributes to loss of productivity and sickness absence. Treatment of common mental disorders in a work setting may improve symptoms, however, that does not automatically lead to improved work productivity. Addressing mental well-being at the workplace might improve work functioning, and digital interventions have been introduced with that objective. However, their evaluation in research has been limited.

The European Intervention to Promote Wellbeing and Health in the Workplace (EMPOWER) digital intervention is designed to provide and evaluate an integrative user programme that meets the needs of employees and employers in addressing work stress.

This work was supported by the European Union Horizon 2020 Research and Innovation Programme Health (grant number APP1195937, 848180). The EMPOWER project started 1.1.2020 and is currently ongoing.

We aim to

1) describe the design and development of the digital intervention.

2) culturally validate the intervention in three countries

3) test the prototype and beta version for its usability in the RCT to evaluate its effect in four countries that is currently ongoing.

A user-centred design process was followed from January 2020 until November 2021 to create a beta version for usability testing. A tailored algorithm was developed to provide support at the individual employee level and the company level. Each element of the digital intervention was translated and culturally validated in four languages in Spain, the United Kingdom, Poland, and Finland. Usability testing was conducted in each country (n=31) to explore validity, usability, and user experience.

The digital intervention consists of a website and a mobile application (app). The website has a public section and an employer portal that provides recommendations to reduce psychosocial risks in their company based upon clustered input from employees. The app provides algorithm-based personalised content after assessing a user’s physical and psychological symptoms, work functioning, and psychosocial risk factors for work stress. The usability testing improved the flow through the app and high ease of use and completion of tasks by participants.

The EMPOWER digital intervention is a tailored multimodal intervention addressing wellbeing, work stress, mental and physical health problems, and work productivity. Usability testing provided validation of the app as version to be evaluated in the EMPOWER RCT.

None Declared

Schizophrenia spectrum disorders (SSD) are frequently associated with disturbances in both neurocognition and social cognition. The patoetiology of SSD derives from a complex interaction between genes and environment. Exposome score for schizophrenia (ES-SCZ) is a cumulative environmental exposure score for schizophrenia which have shown potential utility in risk stratification and outcome prediction.

To investigate whether ES-SCZ is associated with cognition in patients with SSD, unaffected siblings, and healthy controls.

The present cross-sectional study included 1141 patients with SSD, 1332 unaffected siblings, and 1495 healthy controls, recruited in the Netherlands, Spain, Serbia, and Turkey. The Wechsler Adult Intelligence Scale (WAIS) was used to evaluate neurocognition, while the Degraded Facial Emotion Recognition (DFAR) task was used to assess social cognition. ES-SCZ was calculated based on our previously validated method. Associations between ES-SCZ and cognitive domains were analyzed by applying regression models in each group (patients, siblings, and controls), adjusted by age, sex, and country.

According to our preliminary analyses, no significant associations were found between ES-SCZ and cognition in patients with SSD. ES-SCZ was negatively associated with WAIS in unaffected siblings (B=−0.40, p=0.03) and controls (B=-0.63, p=0.004) and positively associated with DFAR in siblings (B=0.83, p=0.004). No significant association between ES-SCZ and DFAR was found in healthy controls.

Our findings show that neurocognition and social cognition are oppositely associated with ES-SCZ. Longitudinal studies may clarify whether there is a cause-effect relationship between ES-SCZ and cognition. Further research should investigate whether ES-SCZ interacts with molecular genetic risk for schizophrenia to improve clinical chcracterization and outcome prediction in people with SSD.

None Declared

Autism spectrum disorder (ASD) is a heterogenous groups of neurodevelopmental conditions characterized by difficulties in social communication and the presence of restricted interests and repetitive behaviors. Autistic traits are distributed along a continuum in the general population and are negatively associated with social functioning also in non-autistic subjects. Several studies have evaluated the association between autistic traits and the quantity of social interaction; however, evidence on the relationship between autistic traits and quality of social interaction is still scarce.

To evaluate the association between autistic traits and the quality of social interactions in daily life in youths from the general population using the experience samplic method (ESM).

During a six-day experience sampling period, 349 twins and 248 of their siblings aged between 15 and 34 reported the quality of their everyday social interactions. Autistic traits were assesed using the Autism Spectrum Quotient (AQ). The association between autistic traits and quality of social interaction was tested in separate multilevel linear and logistic regression models.

When participants were alone, higher autistic traits were associated with a sense of being less safe (B=-0.02, p=0.02). When participants were in company, higher autistic traits were associated with a higher preference for being alone (B=0.02, p<0.001) and higher sense of being judged (B=0.03, p=0.001). Moreover, while in company, higher autistic traits were associated with a decreased pleasure of being in company (B=-0.03, p<0.001), a lower sense of being safe in company (B=-0.03, p<0.001), and a lower sense of belonging to a group (B=-0.02, p<0.001).

The preliminary results of the present study showed that autistic traits may influence the quality of social interactions in daily life. Future studies may clarify the mechanisms underlying this association. Assessing autistic traits in youth may help improve the outcome of psychosocial interventions of youths presenting difficulties in social interactions.

None Declared

Neuroticism has societal, mental and physical health relevance, with an etiology involving genetic predisposition, psychological influence, and their interaction.

To understand whether the association between polygenic risk score for neuroticism (PRS-N) and neuroticism is moderated by affective well-being.

Data were derived from TwinssCan, a general population twin cohort (age range=15-35 years, 478 monozygotic twins). Self-report questionnaires were used to measure well-being and neuroticism. PRS-N was trained from the Genetics of Personality Consortium (GPC) and United Kingdom Biobank (UKB). Multilevel mixed-effects models were used to test baseline and changes in well-being and neuroticism.

Baseline wellbeing and neuroticism were associated (β=-1.35, p<0.001). PRSs-N were associated with baseline neuroticism (lowest p-value: 0.008 in GPC, 0.01 in UKB). In interaction models (PRS x wellbeing), GPC PRS-N (β=0.38, p=0.04) and UKB PRS-N (β=0.81, p<0.001) had significant interactions.

PRSs-N were associated with changes in neuroticism (lowest p-value: 0.03 in GPC, 0.3 in UKB). Furthermore, changes in wellbeing and neuroticism were associated (β =-0.66, p<0.001). In interaction models (PRS x change in wellbeing), only UKB PRS-N had a significant interaction (β=0.80, p<0.001).

Interaction between polygenic risk, wellbeing and neuroticism, were observed regarding baselines measures and change over time. Depending on the analysis step, the direction of the effect changed.

None Declared

Prior evidence suggests that men and women might be differentially susceptible to distinct types of childhood adversity (CA), but research on gender-specific associations between CA subtypes and psychiatric symptoms is limited.

To test the gender-specific associations of CA subtypes and psychiatric symptoms in the general population.

Data from 791 twins and siblings from the TwinssCan project were used. Psychopathology and CA exposure were assessed using the Symptom Checklist-90 Revised (SCL-90) and the Childhood Trauma Questionnaire (CTQ), respectively. The associations between the total CTQ scores and SCL-90 scores (i.e. total SCL-90, psychoticism, paranoid ideation, anxiety, depression, somatization, obsessive-compulsive, interpersonal sensitivity, hostility, and phobic anxiety) were tested in men and women separately. The associations between the five CA subtypes (i.e. physical abuse, emotional abuse, sexual abuse, physical neglect, and emotional neglect) and total SCL-90 were tested in a mutually adjusted model. As exploratory analyses, the associations between all CA subtypes and the nine SCL-90 subdomain scores were similarly tested. The regression coefficients between men and women were compared using Chow’s test. All models were adjusted for age and family structure.

Total CTQ was significantly associated with total SCL-90 in men (B = 0.013, SE = 0.003, P < .001) and women (B = 0.011, SE = 0.002, P < .001). The associations with the nine symptom domains were also significant in both genders (P < .001). No significant gender differences in the regression coefficients of total CTQ were detected. The analyses of CA subtypes showed a significant association between emotional abuse and total SCL-90 in women (B = 0.173, SE = 0.030, P < .001) and men (B = 0.080, SE = 0.035, P = .023), but the association was significantly stronger in women (ꭓ2(1) = 4.10, P = .043). The association of sexual abuse and total SCL-90 was only significant in women (B = 0.217, SE = 0.053, P < .001). The associations of emotional neglect (B = 0.061, SE = 0.027, P = .026) and physical neglect (B = 0.167, SE = 0.043, P < .001) with total SCL-90 were only significant in men. The explorative analyses of SCL-90 subdomains revealed significant associations of emotional abuse with all nine symptom domains and of sexual abuse with seven symptom domains in women. Significant associations of physical neglect with six symptom domains and of emotional neglect with depression were also detected in men. No other significant associations between CT subtypes and total SCL-90 or symptom domain scores were observed in men and women.

CA exposure was associated with diverse psychopathology similarly in both genders. However, women are more sensitive to abuse, but men are more sensitive to neglect. Gender-specific influences of CA subtypes on psychopathology should be considered in future studies.

None Declared

Tobacco is a highly prevalent substance of abuse in patients with psychosis. Previous studies have reported an association between tobacco use and schizophrenia. The aim of this study was to analyze the relationship between tobacco use and first-episode psychosis (FEP), age at onset of psychosis, and specific diagnosis of psychosis.

The sample consisted of 1105 FEP patients and 1355 controls from the European Network of National Schizophrenia Networks Studying Gene–Environment Interactions (EU-GEI) study. We assessed substance use with the Tobacco and Alcohol Questionnaire and performed a series of regression analyses using case-control status, age of onset of psychosis, and diagnosis as outcomes and tobacco use and frequency of tobacco use as predictors. Analyses were adjusted for sociodemographic characteristics, alcohol, and cannabis use.

After controlling for cannabis use, FEP patients were 2.6 times more likely to use tobacco [p ⩽ 0.001; adjusted odds ratio (AOR) 2.6; 95% confidence interval (CI) [2.1–3.2]] and 1.7 times more likely to smoke 20 or more cigarettes a day (p = 0.003; AOR 1.7; 95% CI [1.2–2.4]) than controls. Tobacco use was associated with an earlier age at psychosis onset (β = −2.3; p ⩽ 0.001; 95% CI [−3.7 to −0.9]) and was 1.3 times more frequent in FEP patients with a diagnosis of schizophrenia than in other diagnoses of psychosis (AOR 1.3; 95% CI [1.0–1.8]); however, these results were no longer significant after controlling for cannabis use.

Tobacco and heavy-tobacco use are associated with increased odds of FEP. These findings further support the relevance of tobacco prevention in young populations.

Adverse childhood experiences (ACE) can affect educational attainments, but little is known about their impact on educational achievements in people at clinical high risk of psychosis (CHR).

In total, 344 CHR individuals and 67 healthy controls (HC) were recruited as part of the European Community’s Seventh Framework Programme-funded multicenter study the European Network of National Schizophrenia Networks Studying Gene–Environment Interactions (EU-GEI). The brief version of the Child Trauma Questionnaire was used to measure ACE, while educational attainments were assessed using a semi-structured interview.

At baseline, compared with HC, the CHR group spent less time in education and had higher rates of ACE, lower rates of employment, and lower estimated intelligence quotient (IQ). Across both groups, the total number of ACE was associated with fewer days in education and lower level of education. Emotional abuse was associated with fewer days in education in HC. Emotional neglect was associated with a lower level of education in CHR, while sexual abuse was associated with a lower level of education in HC. In the CHR group, the total number of ACE, physical abuse, and neglect was significantly associated with unemployment, while emotional neglect was associated with employment.

ACE are strongly associated with developmental outcomes such as educational achievement. Early intervention for psychosis programs should aim at integrating specific interventions to support young CHR people in their educational and vocational recovery. More generally, public health and social interventions focused on the prevention of ACE (or reduce their impact if ACE occur) are recommended.