Christian Rück

The use of prescribed benzodiazepines and related Z-drugs (BZDR) was suggested to influence the risk of suicide attempts and suicides, but research findings are inconsistent. In Sweden, BZDRs are the second most used psychotropics and prescriptions mainly come from primary care. Hence, it is important to equip prescribers with evidence-based strategies on how to map and prevent suicidal behaviours among BZDR recipients.The purpose of the project is to combine epidemiological methods with the “real-world” experiences of prescribers from primary care to explore how the use of prescribed BZDRs impacts suicidal behaviour in patients with various underlying disorders and how to enhance safer BZDR prescribing to reduce such risks.In Aim 1, we will use the Swedish registers and multiple causal inference designs to uncover the causal effect of prescribed BZDR use on patients’ suicidal behaviours. In Aim 2, sequence analysis will be applied to register data to determine BZDR prescribing patterns associated with attempted and completed suicides and to identify the patients’ risk groups. In Aim 3, together with general practitioners, we will explore their perceptions of suicidal behaviour risk in BZDR recipients and co-create an actionable strategy to better support prescribers in making informed decisions on BZDR treatment to prevent such risks.In-depth knowledge on how prescribed BZDR use may affect suicidal behaviours is crucial for saving lives of patients undergoing BZDR treatment.

Obsessive-compulsive disorder (OCD) is a heritable psychiatric disorder associated with substantial personal and societal costs. Genomics has the potential to identify molecular risk mechanisms and accelerate the discovery of new treatments. In the current proposal, we aim to advance OCD risk gene discovery by focusing on early onset cases, which are known to be particularly heritable. In Aim 1, we will first generate new whole-exome sequencing (WES) data from 200 Swedish trios (mom, dad, and OCD-affected child), as well as early onset OCD cases (N = 1,200). We will also generate N = 200 within-batch controls and add 5,000 existing Swedish control exomes. Next, we will carefully harmonize all worldwide OCD WES data with our data and perform a meta-analysis of approximately 1,200 trios, 13,000 cases, and 45,000 controls. This will represent the first large-scale analysis of rare coding variants in OCD. In Aim 2, we will conduct a novel cross-species gene network analysis by integrating human OCD GWAS and WES results with data we have generated for canine compulsive disorder, a plausible animal model. In Aim 3, we will evaluate whether OCD genomic findings implicate specific brain regions and cell types by combining OCD GWAS and WES results with bulk tissue and single-cell gene expression atlases. We expect to deliver robust rare coding variant discoveries for OCD and help translate OCD genomic results into an improved mechanistic understanding of the disorder.

The Centre for Applied Psychiatric Research and Innovation (CAPRI) will focus on individuals with severe psychiatric conditions receiving care in high-intensity settings such as inpatient wards, involuntary care, emergency psychiatry, and intensive outpatient programs. These patients are often excluded from clinical trials and underserved by existing evidence-based interventions. CAPRI’s purpose is to close critical knowledge gaps by co-developing, testing, and implementing person-centred interventions with patients, families, clinicians, and social services, aiming to improve outcomes, reduce coercion, promote recovery, and inform policy.CAPRI will be led by researchers at Karolinska Institutet in partnership with researchers from e.g. Uppsala University and the University of Oxford and the health care organization and patient representatives. Our vision is that the generated new knowledge will change inpatient care and  improve outcomes, reduce self-harm and coercion and promote recovery and community integration.CAPRI is organised around four research tracks, each addressing a key challenge for individuals with severe and complex psychiatric conditions:Patient-Centered Innovation in Treatment and Care – develop and evaluate care that improves access to evidence based psychiatric care in complex care settings.Inpatient and involuntary care – improve quality, patient safety, and ethics in contexts where autonomy is restricted and risks are high.Suicide prevention – develop effective strategies in high-intensity care.Changing practice – translate research into clinical routines through implementation science, measurement based care and collaboration with patients, families and clinicians.Together, these tracks will close critical knowledge gaps and drive lasting improvements in psychiatric care where needs are greatest.CAPRI will serve as a research hub located at Karolinska Institutet and working in close partnership with Region Stockholm psychiatry, patient organizations, and social services. The centre unites expertise in psychiatry, psychology, nursing, ethics, social work, and implementation science, supported by dedicated infrastructure, advisory boards, and patient participation structures. Co-creation will be a central aspect across the research at CAPRI, patients and clinicians will be part of the generation of research questions, projects, and design of studies and will review intervention components before they are tested.

Research problem and specific questionsSuicide is a critical public health issue, causing over 700,000 deaths globally annually, with around 1,600 in Sweden. Psychiatric inpatients (psykiatriska slutenvårdspatienter) face a significantly high suicide risk, particularly following recent discharge. Given that prior suicide attempts and self-harm are strong risk factors, there is an urgent need for suicide-specific interventions specifically for those hospitalized after suicide attempts. Brief Cognitive Behavioral Therapy (BCBT) has shown promising results in reducing suicide attempts (60% reduction) and psychiatric readmissions (70% reduction) in a recent U.S. trial. However, key questions remain regarding its replicability, long-term impact, and scalability. This project therefore aims to answer whether BCBT is feasible, effective both short- and long-term, and cost-effective in Swedish inpatient care.Data and methodThis project will evaluate BCBT for suicidal psychiatric inpatients through a pilot study and a randomized controlled trial (RCT). The pilot study, recruiting 20 participants, will assess the feasibility and acceptability of BCBT among suicidal inpatients through questionnaires and qualitative interviews with patients and staff. The RCT, recruiting 246 participants, will evaluate the effect of Treatment as usual (TAU) + BCBT compared to TAU on suicide attempts (primary outcome) and psychiatric readmissions over six months following discharge. Other key outcomes include suicidal ideation, health-related quality of life, cost-effectiveness, and long-term effects on suicide attempts and deaths. Further, a process evaluation will assess implementation factors for future scaling.Societal relevance and utilisationAligned with Fortes’s vision for equitable health, this study addresses a critical gap in suicide prevention research by focusing on inpatient psychiatric care. If proven effective, BCBT could transform inpatient psychiatric care with a scalable, evidence-based intervention, to the benefit of suicidal patients, their families, friends, and clinicians. Plan for project realisationThe project will be conducted at seven psychiatric inpatient wards at Psykiatri Sydväst, Region Stockholm. Our research group has extensive expertise in both trial design and suicidology and already closely collaborates with the clinic. FORTE funding would enable this project, primarily by financing a PhD student and clinicians delivering the treatment.

Research problem and specific questionsSuicide prevention is a high-priority public health goal. Assessing patients´ suicide risk is a basis for clinical decisions in psychiatry, including decisions about involuntary care. However, there is currently a lack of clear evidence on how suicide risk should be assessed and how risk assessments should be used, leading to uncertainty and possible inequality in clinical assessments and decisions.- How are suicide risk assessments conducted and what basis do they provide for clinical decisions, including decisions about involuntary care?- How do patients perceive suicide risk assessments and what is their view on the role of suicide risk assessments in psychiatry?- How do judges perceive suicide risk assessments and what relevance do they have for court decisions regarding involuntary psychiatric care?- How should suicide risk assessments be conducted and how should they be used in healthcare?Data and methods1) Interviews with psychiatrists about how they conduct suicide risk assessments and how they use their assessments. The data will be analyzed using qualitative content analysis.2) Interviews with patients about their experiences and views of suicide risk assessments. We will use thematic analysis to analyse the data.3) A survey study based on case vignettes and questions on suicide risk assessments and involuntary psychiatric care. The survey will be sent to Swedish psychiatrists. We will use descriptive and inferential methods to analyze the results.4) Focus group interviews with judges in the Administrative Courts regarding suicide risk as a reason for involuntary psychiatric care. We will use qualitative content analysis to analyze the data. 5) Ethical analysis based on studies 1-4 and current research on suicide prediction. The aim is to present an analysis and an ethical framework to guide assessments of suicide risk in healthcare.Social Relevance and utilisationThe overarching goal of the project is to provide a basis for evidence-based, clinically meaningful, equal, and patient-centered assessments of suicide risk.Plan for project realisationThe project will be conducted over three years by an interdisciplinary research team that includes expertise in psychiatry, medical ethics, and law. We intend to publish the results in the form of research articles and also to develop a framework for suicide risk assessments to be used as decision support in healthcare

Purpose and aims: There is so much comorbidity among psychiatric conditions that one can combine them into a single general psychopathology index. Although general psychopathology predicts adverse outcomes, it remains unknown if it responds to intervention. Therefore, we will estimate the causal effect of psychosocial interventions and psychotropic medications on general psychopathology. Method: We will apply casual inference designs (children-of-siblings design

co-twin control/within-individual design

instrumental variable

and front-door criterion) to data from the Swedish Twin Register and Swedish population registers to estimate the effect of childrearing conditions (year 1), psychotherapy (years 2-3), and psychotropic medication (years 1-5) on general psychopathology (derived from self/parent-reported symptoms and psychiatric diagnoses). The principal investigator will devote 50% of his time to this project, and he is supported by experts in epidemiology, psychotherapy, and psychiatry. Importance: Even though comorbidity is the rule rather than exception in psychiatry, most randomized clinical trials exclude individuals with several disorders. Therefore, there is a lack of knowledge of the effect of treatment on comorbidity. By applying innovative causal inference designs to large observational data, we aim to study the effect of treatment on general psychopathology in the best conceivable way. This could open a new area of research into transdiagnostic treatments.

Research problem and specific questionsObsessive-compulsive disorder (OCD) is a serious anxiety disorder affecting about 2% of the population which is associated with substantial disability across a range of domains, including educational attainment and participation in the labour market. According to data from the Swedish national registers, 44% of individuals with a diagnosis of OCD will be receiving disability pension, be in long-term sickness absence or be long-term unemployed at some point during their employable years. The overarching purpose of this project is to implement and evaluate the efficacy and cost-effectiveness of Individual Placement and Support (IPS), a person-centred return-to-work program, which has an extensive evidence base in other serious mental disorders but has yet to be evaluated in individuals with OCD.Data and methodThis will be the first evaluation of IPS for OCD anywhere in the world. We propose to partner with service users, interest organisations, clinicians, employment specialists, and clinic managers to first pilot IPS in specialist OCD services (n=20

AIM 1). With lessons learnt from the pilot, we will then optimise the delivery of IPS in this clinical context and conduct a fully powered randomised controlled trial of IPS plus standard specialist OCD treatment, compared standard specialist OCD treatment alone (N=110

AIM 2). Finally, we will evaluate the cost-effectiveness of the intervention from a societal perspective, including a 2-year follow-up in the registers (AIM 3). Societal relevance and utilisationThis proposal originated as a direct response to a demand from service users who struggle to get on with their lives, even after having received a good treatment for their OCD . Many service users wish to return to work but are unable to. If successful, this project could represent a new model for the reintegration of individuals with OCD in the labour market, which will not only contribute to the holistic recovery of the individual, but also have clear socioeconomic benefits for society.Plan for project realisationThe project brings together a multidisciplinary team of researchers with a track record in OCD research, clinical trials, return-to-work interventions, biostatistics, health economics, and implementation science. The team also includes service users and interest organizations that will contribute with their lived experience, as well as health professionals.

Exhaustion disorder (ED, utmattningssyndrom) is one of the most common and costly mental disorders in Swedish primary care. However, the validity of ED is debated and there are no evidence-based treatments. The core of ED - fatigue - is common across a range of disorders. Recent advances in international research indicate that fatigue is best understood as a transdiagnostic symptom dimension rather than a diagnosis-specific pathology. This paves the way for new, potentially more effective, approaches to assessment and treatment.The purpose of this project is to increase knowledge of fatigue as a transdiagnostic symptom in primary care patients and to build evidence for a highly accessible transdiagnostic treatment for fatigue. Consecutively recruited primary care patients (N=500) with fatigue will be included in a multicenter randomized controlled trial and receive internet-delivered transdiagnostic cognitive behavioral therapy adjunct to care as usual, or care as usual only. Primary outcome will be change in fatigue severity (pre-post treatment) with controlled follow-ups up to 2 years from baseline. Moderators and mechanisms of treatment effect, and cost-effectiveness, will be analyzed.This project has the potential to build solid evidence for an accessible, cost-effective treatment of fatigue that can be readily implemented in primary care. Results will contribute to development of guidelines for assessment and treatment of fatigue, and better use of healthcare resources.

Research problem and specific questionsExhaustion disorder (ED, utmattningssyndrom) is one of the most common and costly mental disorders in Sweden, but the validity of ED is debated and there are no evidence-based treatments. The core of ED - fatigue - is common across a range of disorders, associated with work-disability and excess mortality. There is mounting evidence from international research supporting that fatigue should be conceptualized as a transdiagnostic symptom dimension rather than a diagnosis-specific pathology. Cognitive behavioral therapy (CBT) is effective in reducing fatigue across a range of medical conditions by the same change mechanisms. This speaks for a transdiagnostic treatment approach. The purpose of this project is to increase knowledge of fatigue as a transdiagnostic symptom in primary care patients and to evaluate the effect of a highly accessible transdiagnostic CBT for fatigue on symptom reduction and long-term work disability. We also aim to investigate moderators and mediators of treatment effect and treatment cost-effectiveness.Data and method Consecutively recruited primary care patients (N=500) with fatigue (independent of primary diagnosis) will be included in a multicenter randomized clinical trial and receive internet-delivered transdiagnostic CBT adjunct to care as usual, or care as usual only. Primary outcome will be change in fatigue severity (pre-post treatment). Secondary outcomes include self-rated symptoms, functional ability, and objective measures of cognitive impairment. Registry data will be used for analysis of healthcare consumption and sickness absence to the 1-year follow-up. Societal relevance and utilization  Fatigue is associated with suffering, work-disability, and high societal costs. This project can build solid evidence for an accessible, cost-effective treatment for fatigue with the potential to improve functional ability and prevent long-term sickness absence. Results can contribute to development of guidelines for assessment and treatment of fatigue, evidence-based recommendations for sick-leave prescription, and more efficient use of healthcare resources.Plan for project realization:Patients will be recruited from at least 3 primary care centers in Stockholm, using existing infrasturctures for care. The project group is a multidisciplinary team of researchers and clinicians from Karolinska Institutet, Stockholm University, and Amsterdam University Medical Center, Netherlands.