The clinical course of major depressive disorder (MDD) is heterogeneous, and early-onset MDD often has a more severe and complex clinical course. Our goal was to determine whether polygenic scores (PGSs) for psychiatric disorders are associated with treatment trajectories in early-onset MDD treated in secondary care.

Data were drawn from the iPSYCH2015 sample, which includes all individuals born in Denmark between 1981 and 2008 who were treated in secondary care for depression between 1995 and 2015. We selected unrelated individuals of European ancestry with an MDD diagnosis between ages 10–25 (N = 10577). Seven-year trajectories of hospital contacts for depression were modeled using Latent Class Growth Analysis. Associations between PGS for MDD, bipolar disorder, schizophrenia, ADHD, and anorexia and trajectories of MDD contacts were modeled using multinomial logistic regressions.

We identified four trajectory patterns: brief contact (65%), prolonged initial contact (20%), later re-entry (8%), and persistent contact (7%). Relative to the brief contact trajectory, higher PGS for ADHD was associated with a decreased odds of membership in the prolonged initial contact (odds ratio = 1.06, 95% confidence interval = 1.01–1.11) and persistent contact (1.12, 1.03–1.21) trajectories, while PGS-AN was associated with increased odds of membership in the persistent contact trajectory (1.12, 1.03–1.21).

We found significant associations between polygenic liabilities for psychiatric disorders and treatment trajectories in patients with secondary-treated early-onset MDD. These findings help elucidate the relationship between a patient's genetics and their clinical course; however, the effect sizes are small and therefore unlikely to have predictive value in clinical settings.

The OPUS trial is the largest randomized controlled trial (RCT) testing early intervention services with 20-years of follow-up among individuals with a first episode of psychosis in the schizophrenia spectrum.

A total of 547 individuals with first episode psychosis in the schizophrenia spectrum were included into the OPUS I trial between January 1998 - December 2000 and allocated to either two years of early intervention services or treatment as usual. Clinical and trained staff, blinded to the original treatment allocation, performed the five, ten and 20-year follow-up assessments.

The early intervention service consisted of two years of assertive community treatment including social skill training, psychoeducation and family involvement delivered by a multi-disciplinary team (staff patient ratio 1:10). The standard treatment was based on the available community mental health treatment (1:20 –1:30).

A total of 164 participants (30%) of 547 were interviewed at the 20-year follow-up. No significant differences were found between the early intervention group (OPUS-group) compared to the Treatment As Usual group (TAU-group) on global functional levels, psychotic and negative symptom scores after 20 years. Likewise, no differences was found ten to 20-years after randomization between the OPUS-group and TAU-group on days of psychiatric hospitalizations (Incidence Rate Ratio (IRR), 1.202, 95% CI 0.733 - 1.997, P=0.46), or number of outpatient contacts (IRR: 1.197, 95% CI 0.889 - 1.612, P=0.24). Of the entire cohort, 40% were in symptom remission and 18% were in clinical recovery at the 20-year follow-up. The mortality rate 20 years after randomization was 13.1% in the OPUS-group and 15.1% in the TAU group, P=.47.

New initiatives are needed to maintain the positive outcomes achieved after two years of early intervention services

None Declared

Traditional psychotherapeutic interventions show small to moderate effect in treating psychotic symptoms. Virtual reality (VR) assisted treatments has the potential of advancing current psychotherapies for psychotic symptoms by creating virtual environments that can elicit responses (e.g., thoughts, feelings, behaviours) mirroring real-world settings. This presentation will highlight the current research initiatives using virtual reality-based interventions targeting positive and negative symptoms in patients with psychosis.

Main findings from the pilot-studies and randomized clinical trials on computer-based and immersive VR-interventions demonstrate preliminary evidence of VR-based psychotherapy for treating auditory hallucinations and paranoia with large effect sizes (Cohens d= 0.75-0.80). Additionally, pilot data has provided indications as to VR-psychotherapy being feasible and acceptable in treating negative symptoms and may have a large effect on participants achieving their goals and potentially in reducing negative symptoms. No adverse effect has been found related to the VR-interventions.

The promising findings on VR-based interventions for psychosis calls for large-scale randomized clinical trials consolidating the evidence for the effect in treating positive and negative symptoms in psychotic disorders. Cost-effectiveness of these short-term VR-based interventions are essential to inform scalability and implementation. Finally, most of the studies target patients in more chronic/treatment resistant phases of psychosis highlighting the need to investigating the effect in earlier phases of psychosis, that is, first-episode and potentially clinical high-risk states.

None Declared

No significant relationships.

Several initiatives within psychiatric nursing targets Non-suicidal self-injury (NSSI) in DK, but none targets the new phenomenon Digital Self-harm. Digital self-harm involves the use of Social media (SoMe) to harm oneself for example by communicating condescending content about and to oneself through fake profiles, seeking out conflicts to be humiliated, and consciously get others to say vicious things about themselves. Further, images are exchanged showing wounds, broken extremities, etc. and thoughts and feelings are exchanged about suicidal actions as well as methods for both self-harm and suicide actions. We do not know enough about what constitutes the problem nor do we know how to address neither the behavior nor their consequences. Due to conflicting results, more research is needed to understand how media affects NSSI as well as suicidal behavior.

The overall objective of this study is to map, at a national level, how SoMe is used as part of NSSI and suicidal behavior and get insight as to what constitutes the behavior and how we address it through three sub-studies.

The study will be carried out as a mixed method study and includes a systematic review (Study 1), a qualitative part, which will be examined through interviews (Study 2), and finally a quantitative part that will be conducted through questionnaires (Study 3).

The project is ongoing.

Prospects of this study are that the project will create clarity about the essence of the phenomenon of digital self-harm, how NSSI and suicidal behavior is affected and generate enough knowledge to develop interventions aiming digital self-harming and suicidal behavior.

No significant relationships.

No significant relationships.

No significant relationships.

Sleep disorders and psychiatric disease are closely related, and psychiatric diseases are associated with elevated suicide risks. Yet, the association between sleep disorders and suicide remains to be assessed using a consistent measure of sleep disorders.

The aim of this study was to examine whether people with a hospital-diagnosis of sleep disorders had higher suicide rates than people with no diagnosis.

In a cohort study, nationwide data on all persons aged 15+ years living in Denmark during 1980-2016 were analysed. Sleep disorders were identified through diagnoses recorded during contacts to somatic hospitals. Incidence Rate Ratios (IRR) were estimated using Poisson regression models and adjusted for relevant covariates.

In all, 3,674,563 males and 3,688,164 females were included, of whom 82,223 (2.2%, mean age: 50.2, SD: 17.5) males and 40,003 (1.1%, mean age: 50.6, SD: 19.9) females had sleep disorder diagnoses. Compared to those with no sleep disorders, the adjusted IRRs for suicide were 1.6 (95% CI, 1.4-1.7) and 2.2 (95% CI, 1.8-2.6) for males and females with sleep disorders, respectively. Excess rates for narcolepsy were found for males (IRR:1.2, 95% CI, 1.0-1.5) and females (IRR:3.3, 95% CI, 3.0-4.1), and for sleep apnea in males (IRR:1.8, 95% CI, 1.5-2.2). Males and females had IRRs of 4.1 (95% CI, 3.1-5.5) and 7.0 (95% CI, 4.8-10.1), respectively, 6 months after being diagnosed with a sleep disorder.

Sleep disorders were associated with higher suicide rates even after adjusting for pre-existing mental disorders. Our findings suggest attention towards suicidal ideation in patients suffering from sleep disorders is warranted.

Disclosures and Acknowledgements: Adam Spira has received honoraria for serving as a consultant to Merck and from Springer Nature Switzerland AG for guest editing special issues of Current Sleep Medicine Reports. The other authors report no conflict of in

Melatonin is often prescribed to patients experiencing sleep disturbances, which has been linked to elevated risks of suicide. However, it remains to be assessed whether melatonin is associated with suicide and suicide attempts.

We aimed to investigate whether individuals in treatment with melatonin had higher rates of suicide and suicide attempt when compared to individuals not in treatment.

Using longitudinal data on all persons aged 10+ years living in Denmark between 2007-2016 were obtained. Data from the National Prescription Register was used to identify periods of being in treatment with melatonin based on number of tablets and daily defined dose. Suicide and suicide attempt were identified in hospital and cause of death registries.

Among 5,798,923 included individuals, 10,577 (0.18%) were in treatment with melatonin (mean treatment length 50 days). Out of 5,952 individuals who died by suicide, 22 (0.37%) were in melatonin treatment, while 134 (0.53%) out of 25,136 had a first suicide attempt. After adjustment for sex and age-group, people in treatment with melatonin were found to have a higher rate of suicide (IRR: 4.2; 95% CI, 2.7-6.4) and suicide attempt (IRR: 6.7-fold (95% CI, 5.7-7.9) when compared to those not in treatment.

Treatment with melatonin was associated with higher rates of suicide and suicide attempt. The association might be explained through mediators, such as psychiatric comorbidity and sleep disorders. Our findings indicate that attention towards these issues might be warranted.

No significant relationships.

Benzodiazepines and non-benzodiazepines have been linked to a variety of adverse effects including addiction. Long term use of these drugs has been associated with an increased risk of suicide.

We assessed if individuals in treatment with non-benzodiazepine (n-BZD) and benzodiazepine (BZD) had higher rates of suicide when compared to individuals not in treatment with these drugs.

We utilized a cohort design and national longitudinal data on all individuals aged 10 or above who lived in Denmark between 1995 and 2018. Treatment with either n-BZD or BZD was identified via the Danish National Prescription Registry and suicide deaths were identified in the national cause of death registries.

In a total of 6,494,206 individuals, 10,862 males and 4,214 females died by suicide. Of these, 1,220 (11.2%) males and 792 (18.8%) females had been in treatment with n-BZD, resulting in adjusted IRR for suicide of 4.2 (95% CI, 4.0 – 4.5) and 3.4 (95% CI, 3.1 – 3.7) for males and females, respectively, when compared to those not in treatment. In all, 529 (4.8%) males and 395 (9.3%) females who died by suicide had been in treatment with BZD. The IRRs for suicide were 2.4 (95% CI, 2.2 – 2.6) and 2.5 (95% CI, 2.3 – 2.8) for males and females, respectively, and compared to those not in treatment.

In this study we find that those in treatment experienced higher suicide rates than those not in treatment, this persisted when also adjusting for a large variety of covariates.

No significant relationships.

Psychiatric disorders are highly polygenic and show patterns of partner resemblance. Partner resemblance has direct population-level genetic implications if it is caused by assortative mating, but not if it is caused by convergence or social homogamy. Using genetics may help distinguish these different mechanisms. Here, we investigated whether partner resemblance for schizophrenia and bipolar disorder is influenced by assortative mating using polygenic risk scores (PRSs).

PRSs from The Danish High-Risk and Resilience Study—VIA 7 were compared between parents in three subsamples: population-based control parent pairs (N=198), parent pairs where at least one parent had schizophrenia (N=193), and parent pairs where at least one parent had bipolar disorder (N=115).

The PRS for schizophrenia was predictive of schizophrenia in the full sample and showed a significant correlation between parent pairs (r=0.121, p=0.0440), indicative of assortative mating. The PRS for bipolar disorder was also correlated between parent pairs (r=0.162, p=0.0067), but it was not predictive of bipolar disorder in the full sample, limiting the interpretation.

Our study provides genetic evidence for assortative mating for schizophrenia, with important implications for our understanding of the genetics of schizophrenia.

Traumatic brain injury (TBI) can cause long-lasting sequelae that may increase the risk of suicidal or criminal behaviour, but large-scale longitudinal studies are lacking on the link between TBI and events of suicide attempt and violent crime. This study examined the incidence of suicide attempt and violent crime following hospital contact for TBI in a nationwide cohort study.

We used nationwide register data covering all individuals aged 10+ living in Denmark during 1980–2016 (n = 7 783 951). Of these, 587 522 individuals had a hospital contact for TBI. Incidence rate ratios (IRR) were calculated by Poisson regression analyses while adjusted for relevant covariates including other fractures and psychiatric diagnoses.

Individuals with TBI had higher rates of suicide attempt (females IRR, 2.78; 95% CI 2.71–2.85; males IRR, 3.00; 95% CI 2.93–3.08) compared to individuals without TBI in adjusted analyses. Multiple TBI and temporal proximity to TBI were associated with higher rates of suicide attempt. Individuals with TBI had higher rates of violent crime (females IRR, 2.43; 95% CI 2.36–2.49; males IRR, 1.80, 95% CI 1.78–1.82) compared with individuals without TBI. Higher rates of violent crime were found after multiple TBI and temporal proximity to TBI.

This nationwide cohort study found higher rates of suicide attempt and violent crime among individuals with prior hospital diagnosed TBI, compared with individuals without TBI. This emphasises the need for preventive efforts immediately after TBI diagnosis, which might mitigate the risks of a trajectory toward suicidal or violent behaviours.

Sex differences in brain structure and neurodevelopment occur in non-clinical populations. We investigated whether sex had a similar effect on developmental domains amongst boys and girls with a familial risk of schizophrenia (FHR-SZ), bipolar disorder (FHR-BP), and controls.

Through Danish registries, we identified 522 7-year-old children (242 girls) with FHR-SZ, FHR-BP, and controls. We assessed their performance within the domains of neurocognition, motor function, language, social cognition, social behavior, psychopathology, and home environment.

FHR-SZ boys compared with FHR-SZ girls had a higher proportion of disruptive behavior and attention-deficit hyperactivity disorder (ADHD) and exhibited lower performance in manual dexterity, balance, and emotion recognition. No sex differences were found between boys and girls within FHR-BP group. Compared with controls, both FHR-SZ boys and FHR-SZ girls showed impaired processing speed and working memory, had lower levels of global functioning, and were more likely to live in an inadequate home environment. Compared with control boys, FHR-SZ boys showed impaired manual dexterity, social behavior, and social responsiveness, and had a higher proportion of ADHD and disruptive behavior disorder diagnoses. Stress and adjustment disorders were more common in FHR-BP boys compared with control boys. We found no differences between FHR-BP girls and control girls.

Impairment within neurodevelopmental domains associated within FHR-SZ boys v. FHR-SZ girls was most evident among boys, whereas no sex differences were found within the FHR-BP group (FHR-BP boys v. FHR-BP girls). FHR-SZ boys exhibited the highest proportion of early developmental impairments.

No significant relationships.

In this study, we examined the relationship between polygenic liability for depression and number of stressful life events (SLEs) as risk factors for early-onset depression treated in inpatient, outpatient or emergency room settings at psychiatric hospitals in Denmark.

Data were drawn from the iPSYCH2012 case-cohort sample, a population-based sample of individuals born in Denmark between 1981 and 2005. The sample included 18 532 individuals who were diagnosed with depression by a psychiatrist by age 31 years, and a comparison group of 20 184 individuals. Information on SLEs was obtained from nationwide registers and operationalized as a time-varying count variable. Hazard ratios and cumulative incidence rates were estimated using Cox regressions.

Risk for depression increased by 35% with each standard deviation increase in polygenic liability (p < 0.0001), and 36% (p < 0.0001) with each additional SLE. There was a small interaction between polygenic liability and SLEs (β = −0.04, p = 0.0009). The probability of being diagnosed with depression in a hospital-based setting between ages 15 and 31 years ranged from 1.5% among males in the lowest quartile of polygenic liability with 0 events by age 15, to 18.8% among females in the highest quartile of polygenic liability with 4+ events by age 15.

These findings suggest that although there is minimal interaction between polygenic liability and SLEs as risk factors for hospital-treated depression, combining information on these two important risk factors could potentially be useful for identifying high-risk individuals.

During the last decades, a renewed interest for negative symptoms (NS) was brought about by the increased awareness that they interfere severely with real-life functioning, particularly when they are primary and persistent.

In this guidance paper, we provide a systematic review of the evidence and elaborate several recommendations for the conceptualization and assessment of NS in clinical trials and practice.

Expert consensus and systematic reviews have provided guidance for the optimal assessment of primary and persistent negative symptoms; second-generation rating scales, which provide a better assessment of the experiential domains, are available; however, NS are still poorly assessed both in research and clinical settings.

This European Psychiatric Association (EPA) guidance recommends the use of persistent negative symptoms (PNS) construct in the context of clinical trials and highlights the need for further efforts to make the definition of PNS consistent across studies in order to exclude as much as possible secondary negative symptoms. We also encourage clinicians to use second-generation scales, at least to complement first-generation ones.

The EPA guidance further recommends the evidence-based exclusion of several items included in first-generation scales from any NS summary or factor score to improve NS measurement in research and clinical settings. Self-rated instruments are suggested to further complement observer-rated scales in NS assessment.

Several recommendations are provided for the identification of secondary negative symptoms in clinical settings.

The dissemination of this guidance paper may promote the development of national guidelines on negative symptom assessment and ultimately improve the care of people with schizophrenia.

Cerebral glutamate and gamma-aminobutyric acid (GABA) levels might predict clinical outcome in individuals at ultrahigh risk (UHR) for psychosis but have previously primarily been investigated in smaller cohorts. We aimed to study whether baseline levels of glutamate and GABA in anterior cingulate cortex (ACC) and glutamate in thalamus could predict remission status and whether baseline metabolites differed in the remission versus the nonremission group. We also investigated the relationship between baseline metabolite levels and severity of clinical symptoms, functional outcome, and cognitive deficits at follow-up.

About 124 UHR individuals were recruited at baseline. In this, 74 UHR individuals were clinically and cognitively assessed after 12 months, while remission status was available for 81 (25 remission/56 nonremission). Glutamate and GABA levels were assessed at baseline using 3 T proton magnetic resonance spectroscopy. Psychopathology, symptom severity, and remission were assessed with the Comprehensive Assessment of At-Risk Mental States and Clinical Global Impression and functional outcome with the Social and Occupational Functioning Assessment Scale. Cognitive function was estimated with the Cambridge Neuropsychological Test Automated Battery.

There were no differences between baseline glutamate and GABA levels in subjects in the nonremission group compared with the remission group, and baseline metabolites could not predict remission status. However, higher baseline levels of GABA in ACC were associated with clinical global improvement (r = −0.34, N = 51, p = 0.01) in an explorative analysis.

The variety in findings across studies suggests a probable multifactorial influence on clinical outcome in UHR individuals. Future studies should combine multimodal approaches to attempt prediction of long-term outcome.

It is unknown if the positive effects of intensive early intervention programmes are sustainable over time. Duration of untreated psychosis (DUP) is associated with outcome of schizophrenia, and it has been proved that DUP can be shortened. Randomized clinical trials have tested possibilities for interventions in high risk groups.

We conducted a single-blinded randomized controlled trial of two years of specialized assertive early intervention programme (OPUS) versus standard treatment. A total of 547 first-episode patients with first episode psychosis or schizotypal disorder were included in the trial and reinterviewed after one, two and five years. OPUS treatment consisted of ACT with family involvement and social skills training.

At five-year follow-up, the positive effect on psychotic and negative symptoms of the treatment seen after two years had disappeared. A significantly smaller percentage of patients from the experimental group were living in supported housing and were hospitalized fewer days during the five-year period. Among patients with schizotypal disorder, the proportion who had a transition to psychosis after one year was 8.1 vs. 28.0 percent for patients randomized to OPUS vs. standard treatment, respectively. At two-year follow-up the figures were 28.1 vs. 44.0. Duration of untreated psychosis (DUP) median was 48 weeks. Longer DUP was independently associated with more psychotic symptoms at entry and at one-year and two-year follow-up.

Due to previous findings, we have started a new trial in which we will randomize 400 patients to two years versus five years of specialized assertive treatment.