Accurate diagnosis of bipolar disorder (BPD) is difficult in clinical practice, with an average delay between symptom onset and diagnosis of about 7 years. A depressive episode often precedes the first manic episode, making it difficult to distinguish BPD from unipolar major depressive disorder (MDD).

We use genome-wide association analyses (GWAS) to identify differential genetic factors and to develop predictors based on polygenic risk scores (PRS) that may aid early differential diagnosis.

Based on individual genotypes from case–control cohorts of BPD and MDD shared through the Psychiatric Genomics Consortium, we compile case–case–control cohorts, applying a careful quality control procedure. In a resulting cohort of 51 149 individuals (15 532 BPD patients, 12 920 MDD patients and 22 697 controls), we perform a variety of GWAS and PRS analyses.

Although our GWAS is not well powered to identify genome-wide significant loci, we find significant chip heritability and demonstrate the ability of the resulting PRS to distinguish BPD from MDD, including BPD cases with depressive onset (BPD-D). We replicate our PRS findings in an independent Danish cohort (iPSYCH 2015, N = 25 966). We observe strong genetic correlation between our case–case GWAS and that of case–control BPD.

We find that MDD and BPD, including BPD-D are genetically distinct. Our findings support that controls, MDD and BPD patients primarily lie on a continuum of genetic risk. Future studies with larger and richer samples will likely yield a better understanding of these findings and enable the development of better genetic predictors distinguishing BPD and, importantly, BPD-D from MDD.

Temperature increases in the context of climate change affect numerous mental health outcomes. One such relevant outcome is involuntary admissions as these often relate to severe (life)threatening psychiatric conditions. Due to a shortage of studies into this topic, relationships between mean ambient temperature and involuntary admissions have remained largely elusive.

To examine associations between involuntary admissions to psychiatric institutions and various meteorological variables.

Involuntary admissions data from 23 psychiatric institutions in the Netherlands were linked to meteorological data from their respective weather stations. Generalized additive models were used, integrating a restricted maximum likelihood method and thin plate regression splines to preserve generalizability and minimize the risk of overfitting. We thus conducted univariable, seasonally stratified, multivariable, and lagged analyses.

A total of 13,746 involuntary admissions were included over 21,549 days. In univariable and multivariable models, we found significant positive associations with involuntary admissions for ambient temperature and windspeed, with projected increases of up to 0.94% in involuntary admissions per degree Celsius temperature elevation. In the univariable analyses using all data, the strongest associations in terms of significance and explained variance were found for mean ambient temperature (p = 2.5 × 10−6, Variance Explained [r2] = 0.096%) and maximum ambient temperature (p = 8.65 × 10−4, r2 = 0.072%). We did not find evidence that the lagged associations explain the associations for ambient temperature better than the direct associations.

Mean ambient temperature is consistently but weakly associated with involuntary psychiatric admissions. Our findings set the stage for further epidemiological and mechanistic studies into this topic, as well as for modeling studies examining future involuntary psychiatric admissions.

Recent stressful life events (SLE) are a risk factor for psychosis, but limited research has explored how SLEs affect individuals at clinical high risk (CHR) for psychosis. The current study investigated the longitudinal effects of SLEs on functioning and symptom severity in CHR individuals, where we hypothesized CHR would report more SLEs than healthy controls (HC), and SLEs would be associated with poorer outcomes.

The study used longitudinal data from the EU-GEI High Risk study. Data from 331 CHR participants were analyzed to examine the effects of SLEs on changes in functioning, positive and negative symptoms over a 2-year follow-up. We compared the prevalence of SLEs between CHR and HCs, and between CHR who did (CHR-T) and did not (CHR-NT) transition to psychosis.

CHR reported 1.44 more SLEs than HC (p < 0.001), but there was no difference in SLEs between CHR-T and CHR-NT at baseline. Recent SLEs were associated with poorer functioning and more severe positive and negative symptoms in CHR individuals (all p < 0.01) but did not reveal a significant interaction with time.

CHR individuals who had experienced recent SLEs exhibited poorer functioning and more severe symptoms. However, as the interaction between SLEs and time was not significant, this suggests SLEs did not contribute to a worsening of symptoms and functioning over the study period. SLEs could be a key risk factor to becoming CHR for psychosis, however further work is required to inform when early intervention strategies mitigating against the effects of stress are most effective.

To understand healthcare workers’ (HCWs) beliefs and practices toward blood culture (BCx) use.

Cross-sectional electronic survey and semi-structured interviews.

Academic hospitals in the United States.

HCWs involved in BCx ordering and collection in adult intensive care units (ICU) and wards.

We administered an anonymous electronic survey to HCWs and conducted semi-structured interviews with unit staff and quality improvement (QI) leaders in these institutions to understand their perspectives regarding BCx stewardship between February and November 2023.

Of 314 HCWs who responded to the survey, most (67.4%) were physicians and were involved in BCx ordering (82.3%). Most survey respondents reported that clinicians had a low threshold to culture patients for fever (84.4%) and agreed they could safely reduce the number of BCx obtained in their units (65%). However, only half of them believed BCx was overused. Although most made BCx decisions as a team (74.1%), a minority reported these team discussions occurred daily (42.4%). A third of respondents reported not usually collecting the correct volume per BCx bottle, half were unaware of the improved sensitivity of 2 BCx sets, and most were unsure of the nationally recommended BCx contamination threshold (87.5%). Knowledge regarding the utility of BCx for common infections was limited.

HCWs’ understanding of best collection practices and yield of BCx was limited.

Cannabis use and familial vulnerability to psychosis have been associated with social cognition deficits. This study examined the potential relationship between cannabis use and cognitive biases underlying social cognition and functioning in patients with first episode psychosis (FEP), their siblings, and controls.

We analyzed a sample of 543 participants with FEP, 203 siblings, and 1168 controls from the EU-GEI study using a correlational design. We used logistic regression analyses to examine the influence of clinical group, lifetime cannabis use frequency, and potency of cannabis use on cognitive biases, accounting for demographic and cognitive variables.

FEP patients showed increased odds of facial recognition processing (FRP) deficits (OR = 1.642, CI 1.123–2.402) relative to controls but not of speech illusions (SI) or jumping to conclusions (JTC) bias, with no statistically significant differences relative to siblings. Daily and occasional lifetime cannabis use were associated with decreased odds of SI (OR = 0.605, CI 0.368–0.997 and OR = 0.646, CI 0.457–0.913 respectively) and JTC bias (OR = 0.625, CI 0.422–0.925 and OR = 0.602, CI 0.460–0.787 respectively) compared with lifetime abstinence, but not with FRP deficits, in the whole sample. Within the cannabis user group, low-potency cannabis use was associated with increased odds of SI (OR = 1.829, CI 1.297–2.578, FRP deficits (OR = 1.393, CI 1.031–1.882, and JTC (OR = 1.661, CI 1.271–2.171) relative to high-potency cannabis use, with comparable effects in the three clinical groups.

Our findings suggest increased odds of cognitive biases in FEP patients who have never used cannabis and in low-potency users. Future studies should elucidate this association and its potential implications.

There is increasing concern over the mental distress of youth in recent years, which may impact mental healthcare utilisation. Here we aim to examine temporal patterns of mental healthcare expenditures in the Netherlands by age and sex in the period between 2015 and 2021.

Comprehensive data from health insurers in the Netherlands at the 3-number postal code level were used for cluster weighted linear regressions to examine temporal patterns of mental healthcare expenditure by age group (18–34 vs 35–65). The same was done for medical specialist and general practitioner costs. Additionally, we examined interactions with gender, by adding the interaction between age, year and sex to the model.

Mental healthcare costs for younger adults (18–34) were higher than those for older adults (35–65) at all time points (β = 0.22, 95%-CI = 0.19; 0.25). Furthermore there was an increase in the strength of the association between younger age and mental healthcare costs from β = 0.22 (95%-CI = 0.19; 0.25) in 2015 to β = 0.37 (95%-CI = 0.35; 0.40) in 2021 (p < 0.0001) and this was most evident in women (p < 0.0001). Younger age was associated with lower general practitioner costs at all time points, but this association weakened over time. Younger age was also associated with lower medical specialist costs, which did not weaken over time.

Young adults, particularly young women, account for an increasing share of mental healthcare expenditure in the Netherlands. This suggests that mental distress in young people is increasingly met by a response from the medical system. To mitigate this trend a public mental health approach is needed.

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.

None Declared

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.